SAE Feature Dashboard

Feature 94

1,055,040 activations

Top Activating Genes

C16orf95-DT act: 68.71 (99.0%ile) | freq: 3353/1055040 (0.32%)

SNHG19 act: 67.25 (98.0%ile) | freq: 38817/1055040 (3.68%)

COA6-AS1 act: 66.99 (97.0%ile) | freq: 23161/1055040 (2.20%)

LINC01023 act: 66.79 (96.0%ile) | freq: 9317/1055040 (0.88%)

SNHG21 act: 66.52 (95.0%ile) | freq: 16923/1055040 (1.60%)

MHENCR act: 65.70 (94.0%ile) | freq: 31002/1055040 (2.94%)

MINCR act: 65.21 (93.0%ile) | freq: 18158/1055040 (1.72%)

ENSG00000268403.3 act: 65.19 (92.0%ile) | freq: 10229/1055040 (0.97%)

SNHG10 act: 64.36 (91.0%ile) | freq: 25238/1055040 (2.39%)

MTHFD2L act: 63.47 (90.0%ile) | freq: 53906/1055040 (5.11%)

🔬 Biological Validation

No significant enrichments found

Feature 236

1,055,040 activations

Top Activating Genes

AHNAK act: 64.50 (99.0%ile) | freq: 171300/1055040 (16.24%)

MAP4 act: 59.98 (98.0%ile) | freq: 131363/1055040 (12.45%)

KATNAL1 act: 57.43 (97.0%ile) | freq: 37256/1055040 (3.53%)

TBCB act: 56.69 (96.0%ile) | freq: 163291/1055040 (15.48%)

IQGAP1 act: 51.87 (95.0%ile) | freq: 241364/1055040 (22.88%)

OPTN act: 51.75 (94.0%ile) | freq: 123382/1055040 (11.69%)

FBXL2 act: 51.71 (93.0%ile) | freq: 32107/1055040 (3.04%)

FAM177A1 act: 50.83 (92.0%ile) | freq: 159254/1055040 (15.09%)

PRMT2 act: 50.72 (91.0%ile) | freq: 172068/1055040 (16.31%)

PCMT1 act: 50.34 (90.0%ile) | freq: 140067/1055040 (13.28%)

🔬 Biological Validation

PPL protein levels

gwas p=1.09e-04 (2 genes)

OMIM:187900

hpo_diseases p=7.94e-04 (15 genes)

Hyperkeratosis

Hyperkeratosis is a histopathological term defining a thickened stratum corneum and may be present in many different skin conditions, with many possible overlaps. Hyperkeratosis refers to the increased thickness of the stratum corneum, the outer layer of the skin. Hyperkeratosis is subclassified as orthokeratotic or parakeratotic. Orthokeratotic hyperkeratosis refers to the thickening of the keratin layer with preserved keratinocyte maturation, while parakeratotic hyperkeratosis shows retained nuclei as a sign of delayed maturation of keratinocytes.

hpo_phenotypes p=3.45e-03 (4 genes)

Ankylosis

A reduction of joint mobility resulting from changes involving the articular surfaces.

hpo_phenotypes p=5.70e-03 (2 genes)

Obstructive sleep apnea

Obstructive Sleep Apnea is a condition characterized by the obstruction of the airway and pauses in breathing during sleep, which occur multiple times throughout the night. It is related to the relaxation of muscle tone that typically happens during sleep, leading to a partial collapse of the soft tissues in the airway and causing airflow obstruction.

hpo_phenotypes p=1.66e-02 (3 genes)

Feature 468

1,055,040 activations

Top Activating Genes

SNHG32 act: 58.16 (99.0%ile) | freq: 146788/1055040 (13.91%)

EIF4A2 act: 55.51 (98.0%ile) | freq: 296034/1055040 (28.06%)

TPPP3 act: 55.38 (97.0%ile) | freq: 48012/1055040 (4.55%)

ATF4 act: 54.18 (96.0%ile) | freq: 198113/1055040 (18.78%)

ID2 act: 53.09 (95.0%ile) | freq: 181704/1055040 (17.22%)

MRFAP1 act: 51.30 (94.0%ile) | freq: 186323/1055040 (17.66%)

RAB1A act: 51.02 (93.0%ile) | freq: 191512/1055040 (18.15%)

SMIM30 act: 49.05 (92.0%ile) | freq: 57029/1055040 (5.41%)

RPS17 act: 46.42 (91.0%ile) | freq: 215916/1055040 (20.47%)

HNRNPA0 act: 44.86 (90.0%ile) | freq: 160583/1055040 (15.22%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=7.39e-06 (15 genes)

Lactic acidosis;Sensorineural hearing loss disorder;Global developmental delay;Hypotonia

clinvar p=1.03e-05 (2 genes)

OMIM:187900

hpo_diseases p=1.16e-05 (15 genes)

Diamond-Blackfan anemia

clinvar p=1.12e-04 (2 genes)

Infantile onset

Onset of signs or symptoms of disease between 28 days to one year of life.

hpo_phenotypes p=5.73e-04 (9 genes)

Feature 611

1,055,040 activations

Top Activating Genes

RPL39 act: 54.59 (99.0%ile) | freq: 481585/1055040 (45.65%)

RPL34 act: 53.61 (98.0%ile) | freq: 528571/1055040 (50.10%)

RPLP0 act: 48.01 (97.0%ile) | freq: 420267/1055040 (39.83%)

RPL7 act: 45.61 (96.0%ile) | freq: 440739/1055040 (41.77%)

RPLP2 act: 45.09 (95.0%ile) | freq: 544807/1055040 (51.64%)

RPL22 act: 42.47 (94.0%ile) | freq: 419959/1055040 (39.81%)

RPL32 act: 41.59 (93.0%ile) | freq: 519826/1055040 (49.27%)

LAPTM4A act: 41.39 (92.0%ile) | freq: 200307/1055040 (18.99%)

FAU act: 41.30 (91.0%ile) | freq: 505777/1055040 (47.94%)

RPS14 act: 41.03 (90.0%ile) | freq: 516145/1055040 (48.92%)

🔬 Biological Validation

Micrognathia

Developmental hypoplasia of the mandible.

hpo_phenotypes p=1.28e-05 (8 genes)

Erythroid hypoplasia

Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.

hpo_phenotypes p=1.04e-04 (3 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=1.30e-04 (2 genes)

OMIM:187900

hpo_diseases p=1.32e-04 (12 genes)

ORPHA:231160

hpo_diseases p=1.52e-04 (11 genes)

Feature 698

1,055,040 activations

Top Activating Genes

TENM4 act: 97.01 (99.0%ile) | freq: 2290/1055040 (0.22%)

GALNT13 act: 95.85 (98.0%ile) | freq: 8512/1055040 (0.81%)

PELI2 act: 95.84 (97.0%ile) | freq: 1176/1055040 (0.11%)

SRGAP1 act: 95.38 (96.0%ile) | freq: 3081/1055040 (0.29%)

GAB2 act: 95.04 (95.0%ile) | freq: 10527/1055040 (1.00%)

ZNF536 act: 94.55 (94.0%ile) | freq: 18190/1055040 (1.72%)

MIR325HG act: 94.45 (93.0%ile) | freq: 3970/1055040 (0.38%)

USP54 act: 94.18 (92.0%ile) | freq: 12715/1055040 (1.21%)

PIK3R1 act: 94.09 (91.0%ile) | freq: 1656/1055040 (0.16%)

SHISA9 act: 93.81 (90.0%ile) | freq: 7832/1055040 (0.74%)

🔬 Biological Validation

Height (baseline)

gwas p=1.13e-05 (16 genes)

SIOPS occupational score (MTAG)

Characteristics of a person such as education and occupation, used to describe the person's position in stratification systems, access to services, etc.

gwas p=1.13e-05 (9 genes)

Waist-hip ratio

The waist circumference measurement divided by the hip circumference measurement. For both men and women, a waist-to-hip ratio (WHR) of 1.0 or higher is considered "at risk" for undesirable health consequences, such as heart disease and ailments associated with OVERWEIGHT. A healthy WHR is 0.90 or less for men, and 0.80 or less for women. (National Center for Chronic Disease Prevention and Health Promotion, 2004)

gwas p=1.22e-04 (8 genes)

Depressed nasal bridge

Posterior positioning of the nasal root in relation to the overall facial profile for age.

hpo_phenotypes p=8.91e-04 (9 genes)

Intellectual disability

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

hpo_phenotypes p=1.67e-03 (11 genes)

Feature 1139

1,055,040 activations

Top Activating Genes

DYNLL1 act: 72.88 (99.0%ile) | freq: 284933/1055040 (27.01%)

EIF4A1 act: 58.82 (98.0%ile) | freq: 140303/1055040 (13.30%)

NPC2 act: 55.16 (97.0%ile) | freq: 223830/1055040 (21.22%)

RPS9 act: 54.82 (96.0%ile) | freq: 463303/1055040 (43.91%)

RPL23A act: 49.26 (95.0%ile) | freq: 449441/1055040 (42.60%)

TUBA1A act: 44.48 (94.0%ile) | freq: 245718/1055040 (23.29%)

IFITM3 act: 42.98 (93.0%ile) | freq: 175407/1055040 (16.63%)

LGALS1 act: 42.97 (92.0%ile) | freq: 262316/1055040 (24.86%)

RPL29 act: 42.77 (91.0%ile) | freq: 457391/1055040 (43.35%)

RPS14 act: 42.72 (90.0%ile) | freq: 513689/1055040 (48.69%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=2.91e-07 (16 genes)

OMIM:187900

hpo_diseases p=5.30e-07 (16 genes)

cirrhosis, familial

Cirrhosis in which no causative agent can be identified.

gencc p=4.20e-06 (2 genes)

Berardinelli-Seip congenital lipodystrophy

A lipodystrophy characterized by the association of lipoatrophy, hypertriglyceridemia, hepatomegaly and acromegaloid features. BSCL belongs to the group of extreme insulin resistance syndromes, which also includes leprechaunism, Rabson-Mendenhall syndrome, acquired generalized lipodystrophy, and types A and B insulin resistance.

gencc p=1.05e-05 (2 genes)

Monogenic diabetes

clinvar p=7.82e-05 (2 genes)

Feature 1175

1,055,040 activations

Top Activating Genes

TUBA4B act: 57.11 (99.0%ile) | freq: 2499/1055040 (0.24%)

DAW1 act: 56.82 (98.0%ile) | freq: 4599/1055040 (0.44%)

FAM166B act: 56.47 (97.0%ile) | freq: 1825/1055040 (0.17%)

C10orf67 act: 56.41 (96.0%ile) | freq: 2000/1055040 (0.19%)

IGFBP7 act: 55.53 (95.0%ile) | freq: 85246/1055040 (8.08%)

SAXO2 act: 55.51 (94.0%ile) | freq: 5910/1055040 (0.56%)

PPP1R32 act: 55.38 (93.0%ile) | freq: 4063/1055040 (0.39%)

DCDC2B act: 54.92 (92.0%ile) | freq: 1257/1055040 (0.12%)

LDLRAD1 act: 54.61 (91.0%ile) | freq: 6670/1055040 (0.63%)

STMND1 act: 54.54 (90.0%ile) | freq: 6782/1055040 (0.64%)

🔬 Biological Validation

Polysplenia

Polysplenia is a congenital disease manifested by multiple small accessory spleens.

hpo_phenotypes p=3.43e-10 (6 genes)

Chronic sinusitis

A chronic form of sinusitis.

hpo_phenotypes p=3.43e-10 (6 genes)

Situs inversus totalis

A left-right reversal (or mirror reflection) of the anatomical location of the major thoracic and abdominal organs.

hpo_phenotypes p=3.43e-10 (7 genes)

Primary ciliary dyskinesia

A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of the patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy).

orphanet p=3.94e-10 (5 genes)

primary ciliary dyskinesia

A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of PCD patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy).

gencc p=5.92e-10 (5 genes)

Feature 1184

1,055,040 activations

Top Activating Genes

RFXANK act: 55.83 (99.0%ile) | freq: 44932/1055040 (4.26%)

PRPF31 act: 54.46 (98.0%ile) | freq: 63699/1055040 (6.04%)

GPS1 act: 53.76 (97.0%ile) | freq: 60285/1055040 (5.71%)

ZDHHC4 act: 53.64 (96.0%ile) | freq: 54934/1055040 (5.21%)

ELOF1 act: 53.32 (95.0%ile) | freq: 69963/1055040 (6.63%)

PEX16 act: 52.76 (94.0%ile) | freq: 59844/1055040 (5.67%)

MLST8 act: 52.69 (93.0%ile) | freq: 44265/1055040 (4.20%)

NUBP2 act: 52.66 (92.0%ile) | freq: 73442/1055040 (6.96%)

GFER act: 52.59 (91.0%ile) | freq: 46696/1055040 (4.43%)

WDR18 act: 52.55 (90.0%ile) | freq: 37817/1055040 (3.58%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=7.60e-04 (12 genes)

retinitis pigmentosa

Retinitis pigmentosa (RP) is an inherited retinal dystrophy leading to progressive loss of the photoreceptors and retinal pigment epithelium and resulting in blindness usually after several decades.

gencc p=3.19e-03 (2 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=2.36e-02 (9 genes)

Hypertonia

A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.

hpo_phenotypes p=2.36e-02 (3 genes)

Failure to thrive

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

hpo_phenotypes p=2.36e-02 (5 genes)

Feature 1232

1,055,040 activations

Top Activating Genes

PTMS act: 75.53 (99.0%ile) | freq: 13009/1055040 (1.23%)

LINC00273 act: 75.07 (98.0%ile) | freq: 15820/1055040 (1.50%)

EGFR act: 71.64 (97.0%ile) | freq: 4873/1055040 (0.46%)

LTB act: 71.61 (96.0%ile) | freq: 2937/1055040 (0.28%)

SHANK2 act: 71.48 (95.0%ile) | freq: 5467/1055040 (0.52%)

YBX3P1 act: 70.44 (94.0%ile) | freq: 289/1055040 (0.03%)

SAMD4A act: 69.33 (93.0%ile) | freq: 2410/1055040 (0.23%)

LYPLA2P2 act: 68.97 (92.0%ile) | freq: 226/1055040 (0.02%)

SLC24A3 act: 68.95 (91.0%ile) | freq: 731/1055040 (0.07%)

INPP4B act: 68.84 (90.0%ile) | freq: 16257/1055040 (1.54%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=3.46e-04 (16 genes)

Platelet distribution width

Measure of variation in platelet size.

gwas p=6.87e-04 (7 genes)

not provided

clinvar p=7.75e-04 (18 genes)

Cat cry

The presence of a characteristic high-pitched cry that sounds similar to the meowing of a kitten.

hpo_phenotypes p=1.07e-03 (2 genes)

Plateletcrit

The proportion of blood volume that is occupied by platelets, expressed as a percentage.

gwas p=1.67e-03 (7 genes)

Feature 1467

1,055,040 activations

Top Activating Genes

LCN2 act: 69.64 (99.0%ile) | freq: 63102/1055040 (5.98%)

HSPB1 act: 67.31 (98.0%ile) | freq: 221329/1055040 (20.98%)

LGALS3 act: 63.97 (97.0%ile) | freq: 225387/1055040 (21.36%)

CTSH act: 52.24 (96.0%ile) | freq: 130267/1055040 (12.35%)

C15orf48 act: 51.25 (95.0%ile) | freq: 145871/1055040 (13.83%)

GDF15 act: 50.41 (94.0%ile) | freq: 33997/1055040 (3.22%)

KRT18 act: 49.25 (93.0%ile) | freq: 90575/1055040 (8.58%)

ANXA2 act: 48.45 (92.0%ile) | freq: 267684/1055040 (25.37%)

ATP1A1 act: 47.17 (91.0%ile) | freq: 194607/1055040 (18.45%)

SERPINA3 act: 44.22 (90.0%ile) | freq: 12544/1055040 (1.19%)

🔬 Biological Validation

cirrhosis, familial

Cirrhosis in which no causative agent can be identified.

gencc p=6.51e-06 (2 genes)

Behavioral variant of frontotemporal dementia

Behavioral variant of frontotemporal dementia (bv-FTD) is a form of frontotemporal dementia (FTD), characterized by progressive behavioral impairment and a decline in executive function with frontal lobe-predominant atrophy.

orphanet p=3.03e-05 (2 genes)

Depression

Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.

hpo_phenotypes p=7.15e-05 (7 genes)

Muscle spasm

Sudden and involuntary contractions of one or more muscles.

hpo_phenotypes p=1.03e-04 (5 genes)

Fasciculations

Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.

hpo_phenotypes p=2.43e-04 (4 genes)

Feature 1690

1,055,040 activations

Top Activating Genes

CXCL1 act: 90.82 (99.0%ile) | freq: 57722/1055040 (5.47%)

CXCL8 act: 89.06 (98.0%ile) | freq: 178635/1055040 (16.93%)

CXCL2 act: 77.49 (97.0%ile) | freq: 113482/1055040 (10.76%)

CXCL3 act: 71.28 (96.0%ile) | freq: 71598/1055040 (6.79%)

IL6 act: 67.06 (95.0%ile) | freq: 9867/1055040 (0.94%)

IL1B act: 64.55 (94.0%ile) | freq: 104546/1055040 (9.91%)

CSF3 act: 63.76 (93.0%ile) | freq: 4826/1055040 (0.46%)

CCL20 act: 61.87 (92.0%ile) | freq: 81907/1055040 (7.76%)

C15orf48 act: 58.99 (91.0%ile) | freq: 145871/1055040 (13.83%)

LCN2 act: 57.97 (90.0%ile) | freq: 63102/1055040 (5.98%)

🔬 Biological Validation

OMIM:612278

hpo_diseases p=5.99e-06 (6 genes)

familial thyroid dyshormonogenesis

A type of primary congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis.

gencc p=9.76e-06 (2 genes)

Familial thyroid dyshormonogenesis

Familial thyroid dyshormonogenesis is a type of primary congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis.

orphanet p=9.76e-06 (2 genes)

CXCL6 levels

gwas p=9.78e-06 (2 genes)

Abnormal circulating thyroglobulin concentration

A deviation from the normal concentration of thyroglobulin, a protein produced in the thyroid gland that acts as a precursor to thyrroid hormones.

hpo_phenotypes p=3.44e-05 (3 genes)

Feature 1970

1,055,040 activations

Top Activating Genes

PTPRCAP act: 53.96 (99.0%ile) | freq: 2246/1055040 (0.21%)

ENSG00000274265.5 act: 48.87 (98.0%ile) | freq: 52050/1055040 (4.93%)

DHFR act: 47.78 (97.0%ile) | freq: 29269/1055040 (2.77%)

RPL18A act: 47.77 (96.0%ile) | freq: 118728/1055040 (11.25%)

ATP6V0C act: 47.39 (95.0%ile) | freq: 15435/1055040 (1.46%)

LINC-PINT act: 47.08 (94.0%ile) | freq: 2970/1055040 (0.28%)

RPL41 act: 47.05 (93.0%ile) | freq: 91470/1055040 (8.67%)

H3-3A act: 46.99 (92.0%ile) | freq: 340370/1055040 (32.26%)

ENSG00000280441.3 act: 46.81 (91.0%ile) | freq: 1390/1055040 (0.13%)

ENSG00000266049.1 act: 45.94 (90.0%ile) | freq: 2614/1055040 (0.25%)

🔬 Biological Validation

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=1.91e-02 (6 genes)

Juvenile onset

Onset of signs or symptoms of disease between the age of 5 and 15 years.

hpo_phenotypes p=1.91e-02 (4 genes)

Chronic constipation

Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.

hpo_phenotypes p=1.91e-02 (2 genes)

Dorsolateral prefrontal thickness (unadjusted for global measures)

Is a quantification of the thickness of brain cortex, e.g. measured by MRI, used in the diagnosis of Alzheimer's disease and other neurological conditions

gwas p=2.29e-02 (2 genes)

Neutrophil percentage of white cells

A calculated measurement in which the number of neutrophil granulocytes is divided by the number of all white blood cells in a specified sample of peripheral venous blood, and the result presented as a ratio, fraction, quotient or percentage. A neutrophil is, or is in the process of becoming, a granular leucocyte having a nucleus with three to five lobes connected by threads of chromatin, cytoplasm containing very fine granules, and which is readily stainable with neutral dyes.

gwas p=2.29e-02 (3 genes)

Feature 2013

1,055,040 activations

Top Activating Genes

ATP5F1E act: 51.59 (99.0%ile) | freq: 474114/1055040 (44.94%)

UQCC2 act: 50.20 (98.0%ile) | freq: 93059/1055040 (8.82%)

NDUFS8 act: 48.76 (97.0%ile) | freq: 154850/1055040 (14.68%)

SLC25A5 act: 47.73 (96.0%ile) | freq: 238363/1055040 (22.59%)

NDUFS6 act: 46.04 (95.0%ile) | freq: 191509/1055040 (18.15%)

UBXN1 act: 45.91 (94.0%ile) | freq: 182349/1055040 (17.28%)

PSMA7 act: 45.15 (93.0%ile) | freq: 312448/1055040 (29.61%)

CCDC107 act: 44.91 (92.0%ile) | freq: 64538/1055040 (6.12%)

MPV17L2 act: 44.72 (91.0%ile) | freq: 20839/1055040 (1.98%)

PFDN2 act: 44.57 (90.0%ile) | freq: 166218/1055040 (15.75%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=1.52e-04 (14 genes)

ORPHA:231160

hpo_diseases p=1.52e-04 (13 genes)

Lactic acidosis

An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.

hpo_phenotypes p=2.40e-04 (5 genes)

Seizure

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

hpo_phenotypes p=3.38e-04 (10 genes)

Hypotonia

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

hpo_phenotypes p=3.38e-04 (10 genes)

Feature 2219

1,055,040 activations

Top Activating Genes

NMT1 act: 80.35 (99.0%ile) | freq: 113923/1055040 (10.80%)

DYNC1I2 act: 77.76 (98.0%ile) | freq: 164396/1055040 (15.58%)

EIF3J act: 75.07 (97.0%ile) | freq: 143456/1055040 (13.60%)

ATP5ME act: 67.86 (96.0%ile) | freq: 316317/1055040 (29.98%)

HES1 act: 66.42 (95.0%ile) | freq: 75207/1055040 (7.13%)

SNHG9 act: 65.96 (94.0%ile) | freq: 117927/1055040 (11.18%)

MIR4458HG act: 63.33 (93.0%ile) | freq: 26296/1055040 (2.49%)

SNHG25 act: 62.01 (92.0%ile) | freq: 121949/1055040 (11.56%)

NDUFB1 act: 61.03 (91.0%ile) | freq: 246800/1055040 (23.39%)

SVIP act: 60.10 (90.0%ile) | freq: 119323/1055040 (11.31%)

🔬 Biological Validation

schizophrenia

A major psychotic disorder characterized by abnormalities in the perception or expression of reality. It affects the cognitive and psychomotor functions. Common clinical signs and symptoms include delusions, hallucinations, disorganized thinking, and retreat from reality.

gencc p=2.97e-03 (2 genes)

Leigh syndrome

A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.

gencc p=2.97e-03 (2 genes)

Small for gestational age

Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.

hpo_phenotypes p=1.38e-02 (3 genes)

Triphalangeal thumb

A thumb with three phalanges in a single, proximo-distal axis. Thus, this term applies if the thumb has an accessory phalanx, leading to a digit like appearance of the thumb.

hpo_phenotypes p=1.38e-02 (2 genes)

Death in childhood

Death in during childhood, defined here as between the ages of 2 and 10 years.

hpo_phenotypes p=2.55e-02 (2 genes)

Feature 2313

1,055,040 activations

Top Activating Genes

CFL1 act: 81.33 (99.0%ile) | freq: 144643/1055040 (13.71%)

RPS24 act: 79.59 (98.0%ile) | freq: 36807/1055040 (3.49%)

SKP1 act: 76.01 (97.0%ile) | freq: 52067/1055040 (4.94%)

BTF3 act: 73.98 (96.0%ile) | freq: 184230/1055040 (17.46%)

PABPC1 act: 73.25 (95.0%ile) | freq: 62983/1055040 (5.97%)

RPS13 act: 73.18 (94.0%ile) | freq: 105151/1055040 (9.97%)

UBB act: 73.17 (93.0%ile) | freq: 146088/1055040 (13.85%)

RPL5 act: 72.93 (92.0%ile) | freq: 96154/1055040 (9.11%)

RPS2 act: 72.70 (91.0%ile) | freq: 52127/1055040 (4.94%)

RPS5 act: 72.63 (90.0%ile) | freq: 294273/1055040 (27.89%)

🔬 Biological Validation

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=6.40e-09 (4 genes)

Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

gencc p=6.50e-09 (4 genes)

Cleft soft palate

Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency.

hpo_phenotypes p=4.47e-08 (5 genes)

Abnormality of the thenar eminence

An abnormality of the thenar eminence, i.e., of the muscle on the palm of the human hand just beneath the thumb.

hpo_phenotypes p=1.03e-07 (4 genes)

Radial artery aplasia

Congenital absence of the radial artery.

hpo_phenotypes p=1.03e-07 (4 genes)

Feature 2736

1,055,040 activations

Top Activating Genes

ID3 act: 83.39 (99.0%ile) | freq: 68878/1055040 (6.53%)

ID1 act: 64.82 (98.0%ile) | freq: 59732/1055040 (5.66%)

KRT7 act: 57.84 (97.0%ile) | freq: 48067/1055040 (4.56%)

ID2 act: 51.82 (96.0%ile) | freq: 181704/1055040 (17.22%)

NFE2L2 act: 51.75 (95.0%ile) | freq: 190367/1055040 (18.04%)

TMEM123 act: 51.74 (94.0%ile) | freq: 180306/1055040 (17.09%)

LGALS3 act: 49.97 (93.0%ile) | freq: 225387/1055040 (21.36%)

ID4 act: 45.03 (92.0%ile) | freq: 27006/1055040 (2.56%)

GLRX act: 45.01 (91.0%ile) | freq: 147803/1055040 (14.01%)

ATOH8 act: 43.66 (90.0%ile) | freq: 7668/1055040 (0.73%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=2.01e-05 (17 genes)

OMIM:187900

hpo_diseases p=3.45e-05 (17 genes)

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=8.23e-04 (12 genes)

Corneal stromal edema

Abnormal accumulation of fluid and swelling of the stroma of cornea.

hpo_phenotypes p=3.83e-03 (2 genes)

Abnormal Descemet membrane morphology

Abnormality of Descemet's membrane, which is the basement membrane of the corneal endothelium.

hpo_phenotypes p=3.83e-03 (2 genes)

Feature 2789

1,055,040 activations

Top Activating Genes

RAB11A act: 108.59 (99.0%ile) | freq: 167361/1055040 (15.86%)

ENSG00000228655.7 act: 57.69 (98.0%ile) | freq: 6860/1055040 (0.65%)

RORA-AS1 act: 56.42 (97.0%ile) | freq: 13717/1055040 (1.30%)

ENSG00000254420.1 act: 55.79 (96.0%ile) | freq: 20099/1055040 (1.91%)

ENSG00000287555.1 act: 55.69 (95.0%ile) | freq: 5438/1055040 (0.52%)

TSIX act: 55.52 (94.0%ile) | freq: 66154/1055040 (6.27%)

IPO9-AS1 act: 54.95 (93.0%ile) | freq: 8133/1055040 (0.77%)

LINC00513 act: 54.40 (92.0%ile) | freq: 51863/1055040 (4.92%)

PCDH9-AS2 act: 53.97 (91.0%ile) | freq: 14284/1055040 (1.35%)

DPYD-AS1 act: 53.52 (90.0%ile) | freq: 14118/1055040 (1.34%)

🔬 Biological Validation

BMI at 1 year old

An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)

gwas p=3.93e-03 (6 genes)

Brain imaging measurements

Non-invasive methods of visualizing and measuring the CENTRAL NERVOUS SYSTEM, especially the brain, by various imaging modalities e.g. CT scan

gwas p=3.93e-03 (4 genes)

Deep white matter hyperintensities

quantification of white matter hyperintensity, usually measured by MRI

gwas p=3.93e-03 (2 genes)

Feature 2849

1,055,040 activations

Top Activating Genes

COMMD10 act: 64.33 (99.0%ile) | freq: 73438/1055040 (6.96%)

ACBD6 act: 61.91 (98.0%ile) | freq: 61534/1055040 (5.83%)

STX8 act: 60.44 (97.0%ile) | freq: 83126/1055040 (7.88%)

FARS2 act: 59.89 (96.0%ile) | freq: 40252/1055040 (3.82%)

SIL1 act: 57.81 (95.0%ile) | freq: 73990/1055040 (7.01%)

ITFG1 act: 57.44 (94.0%ile) | freq: 122146/1055040 (11.58%)

GMDS act: 56.33 (93.0%ile) | freq: 55286/1055040 (5.24%)

COMMD1 act: 56.31 (92.0%ile) | freq: 95933/1055040 (9.09%)

RSU1 act: 55.10 (91.0%ile) | freq: 84981/1055040 (8.05%)

IMMP2L act: 54.98 (90.0%ile) | freq: 54042/1055040 (5.12%)

🔬 Biological Validation

Bone mineral density (paediatric, total body less head)

gwas p=2.76e-04 (11 genes)

Hip shape mode 6

Measurements of the hip.

gwas p=2.76e-04 (5 genes)

RR interval (tricyclic/tetracyclic antidepressant use interaction)

Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tricyclic antidepressant stimulus

gwas p=2.76e-04 (2 genes)

ORPHA:231160

hpo_diseases p=5.45e-04 (16 genes)

Seizure

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

hpo_phenotypes p=2.30e-03 (11 genes)

Feature 2924

1,055,040 activations

Top Activating Genes

TRMT112 act: 65.24 (99.0%ile) | freq: 5742/1055040 (0.54%)

NIPSNAP1 act: 59.41 (98.0%ile) | freq: 2934/1055040 (0.28%)

RPL32 act: 58.54 (97.0%ile) | freq: 169696/1055040 (16.08%)

GRB2 act: 55.69 (96.0%ile) | freq: 25171/1055040 (2.39%)

YWHAZ act: 55.20 (95.0%ile) | freq: 43132/1055040 (4.09%)

APPL1 act: 53.13 (94.0%ile) | freq: 12841/1055040 (1.22%)

TMEM123 act: 52.45 (93.0%ile) | freq: 3663/1055040 (0.35%)

B2M act: 52.35 (92.0%ile) | freq: 330324/1055040 (31.31%)

NAMPT act: 52.10 (91.0%ile) | freq: 167172/1055040 (15.85%)

FNBP4 act: 51.53 (90.0%ile) | freq: 5232/1055040 (0.50%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=2.35e-03 (12 genes)

Polyneuropathy

A generalized disorder of peripheral nerves.

hpo_phenotypes p=3.02e-03 (3 genes)

Brain neoplasm

A benign or malignant neoplasm that arises from or metastasizes to the brain.

hpo_phenotypes p=3.02e-03 (2 genes)

complex neurodevelopmental disorder

A disorder that involves more than one phenotype associated with the central nervous system, including but not limited to intellectual disability, autism, and seizures (epilepsy).

gencc p=6.83e-03 (3 genes)

Leigh syndrome

A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.

gencc p=7.58e-03 (2 genes)

Feature 3122

1,055,040 activations

Top Activating Genes

NCOA6 act: 61.23 (99.0%ile) | freq: 67144/1055040 (6.36%)

RALY act: 60.09 (98.0%ile) | freq: 131346/1055040 (12.45%)

CPNE1 act: 59.28 (97.0%ile) | freq: 98352/1055040 (9.32%)

STAU1 act: 58.13 (96.0%ile) | freq: 130622/1055040 (12.38%)

PSMA7 act: 55.85 (95.0%ile) | freq: 312448/1055040 (29.61%)

PHF20 act: 55.28 (94.0%ile) | freq: 117918/1055040 (11.18%)

RTF2 act: 54.57 (93.0%ile) | freq: 56692/1055040 (5.37%)

YWHAB act: 54.02 (92.0%ile) | freq: 333769/1055040 (31.64%)

DIDO1 act: 53.24 (91.0%ile) | freq: 61435/1055040 (5.82%)

DDX27 act: 53.22 (90.0%ile) | freq: 71621/1055040 (6.79%)

🔬 Biological Validation

Multi-trait sex score

Quantification of the phenotypic difference between males and females, eg within anthropometric or cardiometabolic traits.

gwas p=1.54e-13 (15 genes)

Height (baseline)

gwas p=1.53e-07 (17 genes)

Trigonocephaly

Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput.

hpo_phenotypes p=3.04e-03 (3 genes)

Hepatosplenomegaly

Simultaneous enlargement of the liver and spleen.

hpo_phenotypes p=3.21e-03 (4 genes)

Gastrostomy tube feeding in infancy

Feeding problem necessitating gastrostomy tube feeding.

hpo_phenotypes p=6.24e-03 (3 genes)

Feature 3209

1,055,040 activations

Top Activating Genes

S100A10 act: 55.34 (99.0%ile) | freq: 368677/1055040 (34.94%)

SPINT2 act: 52.91 (98.0%ile) | freq: 141543/1055040 (13.42%)

CD63 act: 49.36 (97.0%ile) | freq: 373768/1055040 (35.43%)

PGK1 act: 46.20 (96.0%ile) | freq: 275089/1055040 (26.07%)

ENO1 act: 43.60 (95.0%ile) | freq: 323488/1055040 (30.66%)

TPI1 act: 43.39 (94.0%ile) | freq: 317577/1055040 (30.10%)

BNIP3 act: 42.90 (93.0%ile) | freq: 124266/1055040 (11.78%)

SERPINB1 act: 42.85 (92.0%ile) | freq: 185448/1055040 (17.58%)

CD9 act: 41.46 (91.0%ile) | freq: 157184/1055040 (14.90%)

CXCL8 act: 41.06 (90.0%ile) | freq: 178635/1055040 (16.93%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=6.49e-04 (13 genes)

Jaundice

Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.

hpo_phenotypes p=1.16e-03 (4 genes)

Increased circulating ferritin concentration

Increased concentration of ferritin in the blood circulation.

hpo_phenotypes p=1.16e-03 (3 genes)

Chronic hemolytic anemia

An chronic form of hemolytic anemia.

hpo_phenotypes p=1.16e-03 (2 genes)

OMIM:612278

hpo_diseases p=1.82e-03 (4 genes)

Feature 3472

1,055,040 activations

Top Activating Genes

MAPK1IP1L act: 39.12 (99.0%ile) | freq: 125537/1055040 (11.90%)

UPF3A act: 38.58 (98.0%ile) | freq: 99301/1055040 (9.41%)

DAP3 act: 38.56 (97.0%ile) | freq: 69240/1055040 (6.56%)

act: 38.42 (96.0%ile) | freq: 388984/1055040 (36.87%)

SPOP act: 37.40 (95.0%ile) | freq: 65197/1055040 (6.18%)

MKRN1 act: 37.37 (94.0%ile) | freq: 85816/1055040 (8.13%)

TM2D1 act: 37.19 (93.0%ile) | freq: 40380/1055040 (3.83%)

UBE2G2 act: 36.99 (92.0%ile) | freq: 39570/1055040 (3.75%)

NDUFS1 act: 36.89 (91.0%ile) | freq: 78972/1055040 (7.49%)

ECHDC1 act: 36.78 (90.0%ile) | freq: 74511/1055040 (7.06%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=1.78e-05 (16 genes)

ORPHA:231160

hpo_diseases p=3.03e-04 (13 genes)

Mitochondrial DNA depletion syndrome 19

clinvar p=4.34e-04 (2 genes)

Mitochondrial disease

clinvar p=4.34e-04 (2 genes)

Leigh syndrome

A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.

gencc p=7.63e-04 (3 genes)

Feature 3499

1,055,040 activations

Top Activating Genes

KIF2A act: 61.10 (99.0%ile) | freq: 92285/1055040 (8.75%)

CAST act: 59.82 (98.0%ile) | freq: 223356/1055040 (21.17%)

H1-3 act: 58.12 (97.0%ile) | freq: 53302/1055040 (5.05%)

JAK1 act: 56.19 (96.0%ile) | freq: 221382/1055040 (20.98%)

EEA1 act: 54.94 (95.0%ile) | freq: 97141/1055040 (9.21%)

LARS1 act: 54.83 (94.0%ile) | freq: 101521/1055040 (9.62%)

H1-4 act: 54.67 (93.0%ile) | freq: 61260/1055040 (5.81%)

ZFR act: 54.42 (92.0%ile) | freq: 106697/1055040 (10.11%)

TAX1BP1 act: 53.94 (91.0%ile) | freq: 214609/1055040 (20.34%)

TMOD3 act: 53.13 (90.0%ile) | freq: 133632/1055040 (12.67%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=5.79e-08 (19 genes)

OMIM:187900

hpo_diseases p=7.85e-07 (18 genes)

Frontal bossing

Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.

hpo_phenotypes p=7.13e-06 (8 genes)

Patent ductus arteriosus

In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.

hpo_phenotypes p=2.68e-05 (7 genes)

Cardiometabolic and hematological traits

gwas p=1.40e-04 (9 genes)

Feature 3695

1,055,040 activations

Top Activating Genes

ANXA2 act: 62.10 (99.0%ile) | freq: 267684/1055040 (25.37%)

AP2S1 act: 56.52 (98.0%ile) | freq: 200179/1055040 (18.97%)

PPIC act: 45.01 (97.0%ile) | freq: 37465/1055040 (3.55%)

GRN act: 43.15 (96.0%ile) | freq: 194810/1055040 (18.46%)

DYNLT1 act: 42.23 (95.0%ile) | freq: 142616/1055040 (13.52%)

CNN3 act: 42.00 (94.0%ile) | freq: 76097/1055040 (7.21%)

S100A16 act: 41.90 (93.0%ile) | freq: 52058/1055040 (4.93%)

MACROH2A1 act: 38.68 (92.0%ile) | freq: 231876/1055040 (21.98%)

ENSA act: 38.59 (91.0%ile) | freq: 154466/1055040 (14.64%)

CAPZB act: 36.32 (90.0%ile) | freq: 259940/1055040 (24.64%)

🔬 Biological Validation

autosomal dominant non-syndromic intellectual disability

Autosomal dominant form of non-syndromic intellectual disability.

gencc p=5.64e-04 (2 genes)

neurodevelopmental disorder

A behavioral and cognitive disorder with onset during the developmental period that involves impaired or aberrant development of intellectual, motor, or social functions.

gencc p=5.64e-04 (3 genes)

Autosomal dominant non-syndromic intellectual disability

orphanet p=1.03e-03 (2 genes)

ORPHA:231160

hpo_diseases p=8.11e-03 (11 genes)

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=1.05e-02 (9 genes)

Feature 3794

1,055,040 activations

Top Activating Genes

S100A10 act: 55.58 (99.0%ile) | freq: 368677/1055040 (34.94%)

TXN act: 52.57 (98.0%ile) | freq: 294626/1055040 (27.93%)

TAGLN2 act: 46.91 (97.0%ile) | freq: 270646/1055040 (25.65%)

NFE2L2 act: 45.01 (96.0%ile) | freq: 190367/1055040 (18.04%)

LAMC2 act: 42.88 (95.0%ile) | freq: 14478/1055040 (1.37%)

CD59 act: 40.85 (94.0%ile) | freq: 152479/1055040 (14.45%)

GSN act: 39.43 (93.0%ile) | freq: 148686/1055040 (14.09%)

ZFP36L1 act: 38.68 (92.0%ile) | freq: 259966/1055040 (24.64%)

MYL12B act: 38.43 (91.0%ile) | freq: 350896/1055040 (33.26%)

YWHAZ act: 37.85 (90.0%ile) | freq: 358291/1055040 (33.96%)

🔬 Biological Validation

Palmoplantar keratoderma

Abnormal thickening of the skin of the palms of the hands and the soles of the feet.

hpo_phenotypes p=1.66e-10 (8 genes)

Abnormal blistering of the skin

The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls.

hpo_phenotypes p=3.91e-09 (7 genes)

Nail dystrophy

Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.

hpo_phenotypes p=5.71e-09 (7 genes)

OMIM:187900

hpo_diseases p=2.79e-08 (21 genes)

ORPHA:231160

hpo_diseases p=1.30e-07 (19 genes)

Feature 3824

1,055,040 activations

Top Activating Genes

DYNC1H1 act: 72.85 (99.0%ile) | freq: 205749/1055040 (19.50%)

AHNAK act: 72.62 (98.0%ile) | freq: 171300/1055040 (16.24%)

SPTAN1 act: 67.71 (97.0%ile) | freq: 131186/1055040 (12.43%)

FLNA act: 67.09 (96.0%ile) | freq: 161084/1055040 (15.27%)

HUWE1 act: 64.15 (95.0%ile) | freq: 115923/1055040 (10.99%)

PLEC act: 63.25 (94.0%ile) | freq: 109898/1055040 (10.42%)

MYH9 act: 63.13 (93.0%ile) | freq: 178841/1055040 (16.95%)

PRPF8 act: 60.81 (92.0%ile) | freq: 110022/1055040 (10.43%)

TLN1 act: 60.48 (91.0%ile) | freq: 161472/1055040 (15.30%)

SPTBN1 act: 58.43 (90.0%ile) | freq: 134408/1055040 (12.74%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=1.17e-19 (35 genes)

OMIM:187900

hpo_diseases p=1.18e-18 (35 genes)

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=3.18e-15 (26 genes)

not provided

clinvar p=1.78e-13 (33 genes)

Global developmental delay

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

hpo_phenotypes p=2.51e-11 (22 genes)

Feature 3975

1,055,040 activations

Top Activating Genes

COX4I1 act: 72.46 (99.0%ile) | freq: 422329/1055040 (40.03%)

HNRNPA1 act: 64.02 (98.0%ile) | freq: 298782/1055040 (28.32%)

RPL32 act: 59.00 (97.0%ile) | freq: 519035/1055040 (49.20%)

RPL19 act: 56.20 (96.0%ile) | freq: 508989/1055040 (48.24%)

CIRBP act: 53.19 (95.0%ile) | freq: 324929/1055040 (30.80%)

ELF3 act: 51.23 (94.0%ile) | freq: 76612/1055040 (7.26%)

EEF1D act: 48.18 (93.0%ile) | freq: 382807/1055040 (36.28%)

RPL4 act: 45.71 (92.0%ile) | freq: 368633/1055040 (34.94%)

PFDN5 act: 43.05 (91.0%ile) | freq: 402145/1055040 (38.12%)

RPL11 act: 43.02 (90.0%ile) | freq: 506753/1055040 (48.03%)

🔬 Biological Validation

Cleft soft palate

Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency.

hpo_phenotypes p=3.68e-05 (4 genes)

Horseshoe kidney

A connection of the right and left kidney by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline.

hpo_phenotypes p=4.86e-05 (5 genes)

Low-set ears

Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.

hpo_phenotypes p=5.63e-05 (8 genes)

ORPHA:231160

hpo_diseases p=2.09e-04 (14 genes)

OMIM:187900

hpo_diseases p=3.93e-03 (12 genes)

Feature 3994

1,055,040 activations

Top Activating Genes

RPL30 act: 56.77 (99.0%ile) | freq: 487485/1055040 (46.21%)

EEF1D act: 51.33 (98.0%ile) | freq: 382813/1055040 (36.28%)

PFDN5 act: 50.91 (97.0%ile) | freq: 402991/1055040 (38.20%)

RPS24 act: 47.93 (96.0%ile) | freq: 512802/1055040 (48.60%)

NACA act: 47.92 (95.0%ile) | freq: 444712/1055040 (42.15%)

DYNLT1 act: 46.50 (94.0%ile) | freq: 142616/1055040 (13.52%)

COMMD6 act: 45.63 (93.0%ile) | freq: 281674/1055040 (26.70%)

FAU act: 44.16 (92.0%ile) | freq: 505460/1055040 (47.91%)

EEF1B2 act: 44.02 (91.0%ile) | freq: 349462/1055040 (33.12%)

RPS21 act: 43.15 (90.0%ile) | freq: 447436/1055040 (42.41%)

🔬 Biological Validation

Low-set ears

Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.

hpo_phenotypes p=5.41e-06 (8 genes)

Micrognathia

Developmental hypoplasia of the mandible.

hpo_phenotypes p=5.41e-06 (8 genes)

Developmental glaucoma

Glaucoma which forms during the early years of a child's life is called developmental or congenital glaucoma.

hpo_phenotypes p=5.41e-06 (4 genes)

Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

gencc p=1.08e-04 (2 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=1.30e-04 (2 genes)

Feature 4508

1,055,040 activations

Top Activating Genes

S100A8 act: 94.37 (99.0%ile) | freq: 173625/1055040 (16.46%)

S100A9 act: 86.22 (98.0%ile) | freq: 197481/1055040 (18.72%)

KRT8 act: 59.46 (97.0%ile) | freq: 96493/1055040 (9.15%)

RPL12 act: 53.97 (96.0%ile) | freq: 469599/1055040 (44.51%)

SFN act: 49.85 (95.0%ile) | freq: 22211/1055040 (2.11%)

LYZ act: 48.98 (94.0%ile) | freq: 144263/1055040 (13.67%)

KRT18 act: 48.59 (93.0%ile) | freq: 90555/1055040 (8.58%)

PIGR act: 46.47 (92.0%ile) | freq: 63859/1055040 (6.05%)

TACSTD2 act: 43.73 (91.0%ile) | freq: 42643/1055040 (4.04%)

CST3 act: 43.11 (90.0%ile) | freq: 300071/1055040 (28.44%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=1.19e-07 (19 genes)

cirrhosis, familial

Cirrhosis in which no causative agent can be identified.

gencc p=1.23e-05 (2 genes)

ORPHA:231160

hpo_diseases p=2.16e-05 (15 genes)

Early infantile developmental and epileptic encephalopathy

A severe form of age-related epileptic encephalopathies characterized by the onset of tonic spasms within the first 3 months of life that can be generalized or lateralized, independent of the sleep cycle, and that can occur hundreds of times per day, leading to psychomotor impairment and death.

orphanet p=3.11e-04 (2 genes)

Conjunctival amyloidosis

A form of amyloidosis that affects the conjunctiva.

hpo_phenotypes p=4.18e-04 (2 genes)

Feature 4635

1,055,040 activations

Top Activating Genes

GLIS3 act: 60.13 (99.0%ile) | freq: 30398/1055040 (2.88%)

NALF1 act: 57.20 (98.0%ile) | freq: 29676/1055040 (2.81%)

EFNA5 act: 56.89 (97.0%ile) | freq: 68881/1055040 (6.53%)

RBMS3 act: 56.69 (96.0%ile) | freq: 44616/1055040 (4.23%)

NRG1 act: 55.97 (95.0%ile) | freq: 24462/1055040 (2.32%)

UNC5D act: 55.49 (94.0%ile) | freq: 16602/1055040 (1.57%)

NRG3 act: 55.28 (93.0%ile) | freq: 27810/1055040 (2.64%)

PLCB1 act: 54.94 (92.0%ile) | freq: 55393/1055040 (5.25%)

PRKG1 act: 54.84 (91.0%ile) | freq: 28571/1055040 (2.71%)

GPC6 act: 54.53 (90.0%ile) | freq: 25865/1055040 (2.45%)

🔬 Biological Validation

Bone mineral density (paediatric, total body less head)

gwas p=9.29e-16 (23 genes)

BMI at 1 year old

An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)

gwas p=6.73e-14 (19 genes)

SIOPS occupational score (MTAG)

Characteristics of a person such as education and occupation, used to describe the person's position in stratification systems, access to services, etc.

gwas p=6.73e-14 (16 genes)

Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Jervell and Lange-Nielsen syndrome 1;Long QT syndrome 1;Short QT syndrome type 2

clinvar p=4.72e-07 (4 genes)

OMIM:187900

hpo_diseases p=1.41e-06 (21 genes)

Feature 5000

1,055,040 activations

Top Activating Genes

CHL1 act: 74.18 (99.0%ile) | freq: 5713/1055040 (0.54%)

CTTNBP2 act: 71.12 (98.0%ile) | freq: 28600/1055040 (2.71%)

ANKRD44 act: 71.06 (97.0%ile) | freq: 27751/1055040 (2.63%)

THRB act: 69.92 (96.0%ile) | freq: 4656/1055040 (0.44%)

ADD3 act: 69.89 (95.0%ile) | freq: 93118/1055040 (8.83%)

KIF5C act: 69.07 (94.0%ile) | freq: 10608/1055040 (1.01%)

SOBP act: 68.71 (93.0%ile) | freq: 8100/1055040 (0.77%)

PRKACB act: 68.46 (92.0%ile) | freq: 20806/1055040 (1.97%)

SYBU act: 68.43 (91.0%ile) | freq: 5638/1055040 (0.53%)

TRIM2 act: 68.41 (90.0%ile) | freq: 12358/1055040 (1.17%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=1.03e-08 (23 genes)

OMIM:187900

hpo_diseases p=1.70e-07 (22 genes)

Short attention span

Reduced attention span characterized by distractibility and impulsivity.

hpo_phenotypes p=5.07e-07 (7 genes)

Juvenile onset

Onset of signs or symptoms of disease between the age of 5 and 15 years.

hpo_phenotypes p=4.02e-04 (9 genes)

Pes cavus

An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).

hpo_phenotypes p=4.02e-04 (6 genes)

Feature 5413

1,055,040 activations

Top Activating Genes

RPS28 act: 60.13 (99.0%ile) | freq: 352688/1055040 (33.43%)

RPL27A act: 59.36 (98.0%ile) | freq: 197607/1055040 (18.73%)

RPL13A act: 59.35 (97.0%ile) | freq: 48757/1055040 (4.62%)

SAT1 act: 59.29 (96.0%ile) | freq: 106431/1055040 (10.09%)

RPS12 act: 59.21 (95.0%ile) | freq: 430482/1055040 (40.80%)

RPS8 act: 59.16 (94.0%ile) | freq: 404988/1055040 (38.39%)

RPLP1 act: 58.86 (93.0%ile) | freq: 522020/1055040 (49.48%)

MT-ND3 act: 57.95 (92.0%ile) | freq: 379109/1055040 (35.93%)

RPL26 act: 57.06 (91.0%ile) | freq: 246923/1055040 (23.40%)

UBC act: 56.80 (90.0%ile) | freq: 360097/1055040 (34.13%)

🔬 Biological Validation

Erythroid hypoplasia

Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.

hpo_phenotypes p=5.99e-22 (10 genes)

Abnormality of the thenar eminence

An abnormality of the thenar eminence, i.e., of the muscle on the palm of the human hand just beneath the thumb.

hpo_phenotypes p=1.64e-20 (9 genes)

Radial artery aplasia

Congenital absence of the radial artery.

hpo_phenotypes p=1.64e-20 (9 genes)

Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

gencc p=1.78e-19 (8 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=2.57e-19 (8 genes)

Feature 5539

1,055,040 activations

Top Activating Genes

CSTB act: 65.32 (99.0%ile) | freq: 337962/1055040 (32.03%)

ATP5IF1 act: 46.08 (98.0%ile) | freq: 238065/1055040 (22.56%)

TMA7 act: 45.57 (97.0%ile) | freq: 383971/1055040 (36.39%)

LMNA act: 40.63 (96.0%ile) | freq: 144412/1055040 (13.69%)

PABPN1 act: 39.59 (95.0%ile) | freq: 118483/1055040 (11.23%)

SQSTM1 act: 39.53 (94.0%ile) | freq: 266779/1055040 (25.29%)

PSMA7 act: 39.41 (93.0%ile) | freq: 312448/1055040 (29.61%)

OAT act: 39.37 (92.0%ile) | freq: 105655/1055040 (10.01%)

ACADVL act: 39.30 (91.0%ile) | freq: 165047/1055040 (15.64%)

ZFP36 act: 38.95 (90.0%ile) | freq: 257624/1055040 (24.42%)

🔬 Biological Validation

Distal muscle weakness

Reduced strength of the musculature of the distal extremities.

hpo_phenotypes p=5.16e-05 (5 genes)

Charcot-Marie-Tooth disease

clinvar p=8.04e-05 (3 genes)

Charcot-Marie-Tooth disease type 2

clinvar p=8.04e-05 (2 genes)

Osteosarcoma

A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.

hpo_phenotypes p=2.52e-04 (3 genes)

Peripheral axonal atrophy

Atrophic changes of axons of the peripheral nervous system.

hpo_phenotypes p=2.52e-04 (2 genes)

Feature 5679

1,055,040 activations

Top Activating Genes

CBLB act: 56.75 (99.0%ile) | freq: 64819/1055040 (6.14%)

DCBLD2 act: 56.04 (98.0%ile) | freq: 28412/1055040 (2.69%)

SLC5A3 act: 55.63 (97.0%ile) | freq: 38583/1055040 (3.66%)

DAAM1 act: 55.58 (96.0%ile) | freq: 33550/1055040 (3.18%)

BAIAP2L1 act: 55.49 (95.0%ile) | freq: 18839/1055040 (1.79%)

ADD3 act: 55.25 (94.0%ile) | freq: 91657/1055040 (8.69%)

FNBP1 act: 54.95 (93.0%ile) | freq: 28886/1055040 (2.74%)

SPATA13_ENSG00000182957 act: 54.95 (92.0%ile) | freq: 40362/1055040 (3.83%)

MAP4K4 act: 54.89 (91.0%ile) | freq: 35059/1055040 (3.32%)

NRIP1 act: 54.70 (90.0%ile) | freq: 18907/1055040 (1.79%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=2.38e-06 (20 genes)

Factor V and factor VIII, combined deficiency of, type 1

clinvar p=1.22e-04 (10 genes)

Height (baseline)

gwas p=1.97e-04 (15 genes)

Platelet distribution width

Measure of variation in platelet size.

gwas p=3.32e-04 (7 genes)

Cortical volume

gwas p=5.49e-04 (3 genes)

Feature 5973

1,055,040 activations

Top Activating Genes

S100A14 act: 57.78 (99.0%ile) | freq: 38607/1055040 (3.66%)

LDHA act: 43.39 (98.0%ile) | freq: 275653/1055040 (26.13%)

RPL22L1 act: 43.26 (97.0%ile) | freq: 146626/1055040 (13.90%)

ZNF706 act: 41.08 (96.0%ile) | freq: 202716/1055040 (19.21%)

GNG5 act: 41.02 (95.0%ile) | freq: 258393/1055040 (24.49%)

S100A16 act: 40.27 (94.0%ile) | freq: 52060/1055040 (4.93%)

EEF1B2 act: 39.93 (93.0%ile) | freq: 350769/1055040 (33.25%)

FAM3C act: 38.30 (92.0%ile) | freq: 107537/1055040 (10.19%)

CLDN7 act: 38.11 (91.0%ile) | freq: 59645/1055040 (5.65%)

EIF4A2 act: 38.08 (90.0%ile) | freq: 296034/1055040 (28.06%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=6.37e-05 (14 genes)

OMIM:187900

hpo_diseases p=8.93e-05 (14 genes)

Abdominal colic

A type of abdominal pain that comes and goes in waves, most often starting and ending suddenly and being of severe intensity.

hpo_phenotypes p=4.18e-04 (2 genes)

Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

orphanet p=2.29e-03 (2 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=2.90e-03 (11 genes)

Feature 6015

1,055,040 activations

Top Activating Genes

VAMP8 act: 48.56 (99.0%ile) | freq: 183984/1055040 (17.44%)

PRDX5 act: 47.41 (98.0%ile) | freq: 236590/1055040 (22.42%)

RBX1 act: 46.05 (97.0%ile) | freq: 192750/1055040 (18.27%)

RPL8 act: 45.48 (96.0%ile) | freq: 491847/1055040 (46.62%)

FKBP8 act: 44.47 (95.0%ile) | freq: 182852/1055040 (17.33%)

SUMO2 act: 42.89 (94.0%ile) | freq: 302468/1055040 (28.67%)

PFDN2 act: 42.85 (93.0%ile) | freq: 166169/1055040 (15.75%)

CYBA act: 42.45 (92.0%ile) | freq: 322146/1055040 (30.53%)

DRAP1 act: 41.56 (91.0%ile) | freq: 193302/1055040 (18.32%)

SLPI act: 39.92 (90.0%ile) | freq: 75350/1055040 (7.14%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=2.08e-04 (12 genes)

OMIM:187900

hpo_diseases p=2.53e-04 (12 genes)

Skin tags

Cutaneous skin tags also known as acrochorda or fibroepithelial polyps are small benign tumors that may either form secondarily over time primarily in areas where the skin forms creases, such as the neck, armpit or groin or may also be present at birth, in which case they usually occur in the periauricular region.

hpo_phenotypes p=6.21e-03 (2 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=6.50e-03 (10 genes)

Pallor

Abnormally pale skin.

hpo_phenotypes p=6.50e-03 (3 genes)

Feature 6200

1,055,040 activations

Top Activating Genes

TSPAN1 act: 59.18 (99.0%ile) | freq: 35420/1055040 (3.36%)

SLC44A4 act: 52.48 (98.0%ile) | freq: 31836/1055040 (3.02%)

CREB3L1 act: 47.05 (97.0%ile) | freq: 16356/1055040 (1.55%)

STARD10 act: 46.19 (96.0%ile) | freq: 66262/1055040 (6.28%)

GALE act: 46.04 (95.0%ile) | freq: 38455/1055040 (3.64%)

EPCAM act: 44.87 (94.0%ile) | freq: 59179/1055040 (5.61%)

FAM3D act: 44.83 (93.0%ile) | freq: 19247/1055040 (1.82%)

RAB25 act: 43.34 (92.0%ile) | freq: 32401/1055040 (3.07%)

SMIM22 act: 43.04 (91.0%ile) | freq: 37819/1055040 (3.58%)

ERN2 act: 42.51 (90.0%ile) | freq: 11216/1055040 (1.06%)

🔬 Biological Validation

Human milk oligosaccharide concentration (lacto-N-tetrose)

gwas p=1.98e-07 (4 genes)

OMIM:187900

hpo_diseases p=4.91e-06 (15 genes)

PCA3 expression level

cancer biomarkers, such as cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein, are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patient

gwas p=4.24e-04 (2 genes)

Elevated serum carcinoembryonic antigen levels

Quantification of carcinoembryonic antigen in serum. Carcinoembryonic antigen is a cancer-specific antigen associated with both tumors and the developing fetus. The main use of this antigen is as a tumor marker, especially with respect to intestinal cancers. Production of the antigen ceases shortly before birth, but may reappear in people who develop certain types of cancer.

gwas p=4.89e-04 (2 genes)

autosomal dominant nonsyndromic hearing loss

Autosomal dominant form of nonsyndromic deafness.

gencc p=6.19e-04 (2 genes)

Feature 6382

1,055,040 activations

Top Activating Genes

RASA2 act: 118.37 (99.0%ile) | freq: 2278/1055040 (0.22%)

BIRC6 act: 117.44 (98.0%ile) | freq: 16564/1055040 (1.57%)

MAML3 act: 117.25 (97.0%ile) | freq: 4978/1055040 (0.47%)

RNMT act: 117.02 (96.0%ile) | freq: 2550/1055040 (0.24%)

MEF2A act: 116.73 (95.0%ile) | freq: 6166/1055040 (0.58%)

CUL3 act: 116.36 (94.0%ile) | freq: 2420/1055040 (0.23%)

GMDS act: 116.11 (93.0%ile) | freq: 2980/1055040 (0.28%)

CAMSAP2 act: 115.85 (92.0%ile) | freq: 6518/1055040 (0.62%)

RB1 act: 114.59 (91.0%ile) | freq: 6681/1055040 (0.63%)

SPAG9 act: 114.27 (90.0%ile) | freq: 19803/1055040 (1.88%)

🔬 Biological Validation

Waist-hip ratio

The waist circumference measurement divided by the hip circumference measurement. For both men and women, a waist-to-hip ratio (WHR) of 1.0 or higher is considered "at risk" for undesirable health consequences, such as heart disease and ailments associated with OVERWEIGHT. A healthy WHR is 0.90 or less for men, and 0.80 or less for women. (National Center for Chronic Disease Prevention and Health Promotion, 2004)

gwas p=3.59e-07 (11 genes)

ORPHA:231160

hpo_diseases p=8.03e-07 (20 genes)

OMIM:187900

hpo_diseases p=1.79e-06 (20 genes)

complex neurodevelopmental disorder

A disorder that involves more than one phenotype associated with the central nervous system, including but not limited to intellectual disability, autism, and seizures (epilepsy).

gencc p=2.12e-06 (6 genes)

Height (baseline)

gwas p=4.61e-06 (17 genes)

Feature 6611

1,055,040 activations

Top Activating Genes

HSPD1 act: 44.70 (99.0%ile) | freq: 187762/1055040 (17.80%)

ODC1 act: 44.35 (98.0%ile) | freq: 62916/1055040 (5.96%)

CCPG1 act: 43.70 (97.0%ile) | freq: 1302/1055040 (0.12%)

HMGB2 act: 43.50 (96.0%ile) | freq: 105058/1055040 (9.96%)

HSPB1 act: 43.47 (95.0%ile) | freq: 97351/1055040 (9.23%)

MBOAT7 act: 43.35 (94.0%ile) | freq: 48517/1055040 (4.60%)

RHOC act: 42.79 (93.0%ile) | freq: 42724/1055040 (4.05%)

PSMD14 act: 42.73 (92.0%ile) | freq: 9875/1055040 (0.94%)

ANXA5 act: 42.27 (91.0%ile) | freq: 39150/1055040 (3.71%)

NUDC act: 42.20 (90.0%ile) | freq: 70240/1055040 (6.66%)

🔬 Biological Validation

Intellectual disability

clinvar p=1.90e-04 (6 genes)

ORPHA:231160

hpo_diseases p=3.01e-04 (14 genes)

OMIM:187900

hpo_diseases p=4.06e-04 (14 genes)

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=1.24e-03 (11 genes)

Adult onset

Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later.

hpo_phenotypes p=1.24e-03 (5 genes)

Feature 6750

1,055,040 activations

Top Activating Genes

GOLT1A act: 60.85 (99.0%ile) | freq: 3278/1055040 (0.31%)

GPR12 act: 60.41 (98.0%ile) | freq: 10334/1055040 (0.98%)

GPR4 act: 60.26 (97.0%ile) | freq: 4443/1055040 (0.42%)

LPAR5 act: 59.79 (96.0%ile) | freq: 2731/1055040 (0.26%)

C1QTNF2 act: 59.74 (95.0%ile) | freq: 1028/1055040 (0.10%)

LMOD3 act: 59.53 (94.0%ile) | freq: 637/1055040 (0.06%)

PHYHD1 act: 59.52 (93.0%ile) | freq: 6121/1055040 (0.58%)

TIE1 act: 59.24 (92.0%ile) | freq: 1384/1055040 (0.13%)

LINC02275 act: 59.20 (91.0%ile) | freq: 192/1055040 (0.02%)

FOXF2 act: 59.18 (90.0%ile) | freq: 68/1055040 (0.01%)

🔬 Biological Validation

Cardiometabolic and hematological traits

The number of PLATELETS per unit volume in a sample of venous BLOOD.

gwas p=8.15e-04 (8 genes)

Monocyte count

quantification of monocytes in the blood

gwas p=8.15e-04 (7 genes)

Protein C levels

Is a quantification of Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV,] is a zymogenic (inactive) protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals.

gwas p=8.15e-04 (2 genes)

Nemaline bodies

Nemaline rods are abnormal bodies that can occur in skeletal muscle fibers. The rods can be observed on histological analysis of muscle biopsy tissue or upon electron microscopy, where they appear either as extensions of sarcomeric Z-lines, in random array without obvious attachment to Z-lines (often in areas devoid of sarcomeres) or in large clusters localized at the sarcolemma or intermyofibrillar spaces.

hpo_phenotypes p=8.42e-03 (2 genes)

Congenital contracture

One or more flexion contractures (a bent joint that cannot be straightened actively or passively) that are present at birth.

hpo_phenotypes p=9.57e-03 (2 genes)

Feature 6792

1,055,040 activations

Top Activating Genes

PPP1CB act: 62.23 (99.0%ile) | freq: 235260/1055040 (22.30%)

HNRNPH1 act: 59.98 (98.0%ile) | freq: 310370/1055040 (29.42%)

ATP1B1 act: 58.62 (97.0%ile) | freq: 200999/1055040 (19.05%)

CTNNB1 act: 55.71 (96.0%ile) | freq: 204337/1055040 (19.37%)

SDC4 act: 53.13 (95.0%ile) | freq: 90120/1055040 (8.54%)

B4GALT1 act: 48.48 (94.0%ile) | freq: 126094/1055040 (11.95%)

TSPYL1 act: 47.13 (93.0%ile) | freq: 115503/1055040 (10.95%)

CHP1 act: 46.18 (92.0%ile) | freq: 83617/1055040 (7.93%)

NUDT19 act: 45.79 (91.0%ile) | freq: 37468/1055040 (3.55%)

CDC42 act: 45.46 (90.0%ile) | freq: 369869/1055040 (35.06%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=6.20e-10 (22 genes)

ORPHA:231160

hpo_diseases p=1.95e-07 (18 genes)

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=5.99e-06 (14 genes)

Hypotonia

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

hpo_phenotypes p=5.99e-06 (13 genes)

Intellectual disability

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

hpo_phenotypes p=6.26e-06 (13 genes)

Feature 7177

1,055,040 activations

Top Activating Genes

PANK2 act: 87.80 (99.0%ile) | freq: 40669/1055040 (3.85%)

CTCF act: 82.29 (98.0%ile) | freq: 59524/1055040 (5.64%)

SSU72 act: 79.63 (97.0%ile) | freq: 191592/1055040 (18.16%)

HGH1 act: 79.51 (96.0%ile) | freq: 5001/1055040 (0.47%)

TMEM248 act: 72.62 (95.0%ile) | freq: 52844/1055040 (5.01%)

PLEKHA3 act: 71.11 (94.0%ile) | freq: 80413/1055040 (7.62%)

MAP2K2 act: 70.76 (93.0%ile) | freq: 100964/1055040 (9.57%)

BRD7 act: 69.52 (92.0%ile) | freq: 104929/1055040 (9.95%)

RRP36 act: 68.89 (91.0%ile) | freq: 26097/1055040 (2.47%)

ATPAF1 act: 68.77 (90.0%ile) | freq: 47767/1055040 (4.53%)

🔬 Biological Validation

Long palpebral fissure

Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures.

hpo_phenotypes p=9.60e-05 (4 genes)

OMIM:187900

hpo_diseases p=7.12e-04 (12 genes)

ORPHA:231160

hpo_diseases p=7.12e-04 (11 genes)

Abnormality of the gastrointestinal tract

An abnormality of the gastrointestinal tract.

hpo_phenotypes p=2.63e-03 (3 genes)

Cryptorchidism

Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum.

hpo_phenotypes p=3.44e-03 (6 genes)

Feature 7333

1,055,040 activations

Top Activating Genes

EZR act: 64.12 (99.0%ile) | freq: 191792/1055040 (18.18%)

LAMB3 act: 58.94 (98.0%ile) | freq: 28932/1055040 (2.74%)

GPRC5A act: 56.63 (97.0%ile) | freq: 45307/1055040 (4.29%)

NDRG1 act: 54.19 (96.0%ile) | freq: 142094/1055040 (13.47%)

ANXA2 act: 53.56 (95.0%ile) | freq: 267684/1055040 (25.37%)

HSP90B1 act: 53.31 (94.0%ile) | freq: 327808/1055040 (31.07%)

YWHAZ act: 52.15 (93.0%ile) | freq: 358352/1055040 (33.97%)

HSP90AB1 act: 51.65 (92.0%ile) | freq: 427863/1055040 (40.55%)

LDHA act: 49.23 (91.0%ile) | freq: 275653/1055040 (26.13%)

PABPC1 act: 47.95 (90.0%ile) | freq: 399005/1055040 (37.82%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=2.01e-08 (21 genes)

OMIM:187900

hpo_diseases p=1.58e-06 (19 genes)

Inborn genetic diseases

clinvar p=7.42e-06 (2 genes)

Junctional epidermolysis bullosa, non-Herlitz type;Junctional epidermolysis bullosa gravis of Herlitz

clinvar p=7.42e-06 (2 genes)

Severe generalized junctional epidermolysis bullosa

A severe form of junctional epidermolysis bullosa (JEB) characterized by blisters and extensive erosions, localized to the skin and mucous membranes.

orphanet p=1.34e-05 (2 genes)

Feature 7355

1,055,040 activations

Top Activating Genes

ICAM1 act: 77.39 (99.0%ile) | freq: 45121/1055040 (4.28%)

RELB act: 76.14 (98.0%ile) | freq: 70006/1055040 (6.64%)

NFKB2 act: 71.34 (97.0%ile) | freq: 69271/1055040 (6.57%)

TNFAIP2 act: 71.21 (96.0%ile) | freq: 84239/1055040 (7.98%)

NFKB1 act: 69.94 (95.0%ile) | freq: 133827/1055040 (12.68%)

NFKBIA act: 69.89 (94.0%ile) | freq: 312623/1055040 (29.63%)

TNIP1 act: 65.87 (93.0%ile) | freq: 128427/1055040 (12.17%)

NINJ1 act: 64.92 (92.0%ile) | freq: 136310/1055040 (12.92%)

SLC2A6 act: 62.59 (91.0%ile) | freq: 41071/1055040 (3.89%)

TNFAIP3 act: 61.92 (90.0%ile) | freq: 171951/1055040 (16.30%)

🔬 Biological Validation

Lymphocyte percentage of white cells

A calculated measurement in which the number of lymphocytes in a specified sample of blood is divided by the total number of white blood cells in the sample, and the result presented as a ratio, fraction, quotient or percentage.

gwas p=1.50e-05 (8 genes)

cardiomyopathy

A disease of the heart muscle or myocardium proper. Cardiomyopathies may be classified as either primary or secondary, on the basis of etiology, or on the pathophysiology of the lesion: hypertrophic, dilated, or restrictive.

gencc p=2.93e-05 (2 genes)

Allergic disease (asthma, hay fever or eczema)

gwas p=6.34e-05 (5 genes)

Systemic sclerosis

A chronic disorder, possibly autoimmune, marked by excessive production of collagen which results in hardening and thickening of body tissues. The two types of systemic scleroderma, limited cutaneous and diffuse cutaneous are classified with focus on the extent of affected skin. A relationship exists between the extent of skin area affected and degree of internal organ/system involvement. Systemic scleroderma can manifest itself in pulmonary fibrosis, Raynaud's syndrome, digestive system telangiectasias, renal hypertension and/or pulmonary hypertension.

gwas p=1.37e-04 (3 genes)

common variable immunodeficiency

Common variable immunodeficiency (CVID) comprises a heterogeneous group of diseases characterized by a significant hypogammaglobulinemia of unknown cause, failure to produce specific antibodies after immunizations and susceptibility to bacterial infections, predominantly caused by encapsulated bacteria.

gencc p=2.21e-04 (2 genes)

Feature 7596

1,055,040 activations

Top Activating Genes

LCN2 act: 88.82 (99.0%ile) | freq: 63102/1055040 (5.98%)

PERP act: 84.79 (98.0%ile) | freq: 76565/1055040 (7.26%)

ELF3 act: 56.48 (97.0%ile) | freq: 76612/1055040 (7.26%)

ALDOA act: 54.80 (96.0%ile) | freq: 203609/1055040 (19.30%)

ATP1B1 act: 50.51 (95.0%ile) | freq: 200999/1055040 (19.05%)

IFNGR1 act: 46.94 (94.0%ile) | freq: 148628/1055040 (14.09%)

CYSTM1 act: 45.83 (93.0%ile) | freq: 163276/1055040 (15.48%)

GPX2 act: 45.74 (92.0%ile) | freq: 41770/1055040 (3.96%)

FAT1 act: 44.70 (91.0%ile) | freq: 31744/1055040 (3.01%)

LINC00511 act: 44.51 (90.0%ile) | freq: 26702/1055040 (2.53%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=1.55e-07 (21 genes)

ORPHA:231160

hpo_diseases p=5.67e-07 (19 genes)

Familial thyroid dyshormonogenesis

Familial thyroid dyshormonogenesis is a type of primary congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis.

orphanet p=4.44e-05 (2 genes)

familial thyroid dyshormonogenesis

A type of primary congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis.

gencc p=8.88e-05 (2 genes)

Nephrotic syndrome

clinvar p=1.55e-04 (2 genes)

Feature 7699

1,055,040 activations

Top Activating Genes

SSR4 act: 93.55 (99.0%ile) | freq: 283015/1055040 (26.83%)

FKBP2 act: 69.01 (98.0%ile) | freq: 208382/1055040 (19.75%)

KRTCAP2 act: 65.77 (97.0%ile) | freq: 184815/1055040 (17.52%)

PRDX4 act: 60.42 (96.0%ile) | freq: 108051/1055040 (10.24%)

MYDGF act: 58.43 (95.0%ile) | freq: 147171/1055040 (13.95%)

SEC11C act: 58.12 (94.0%ile) | freq: 174113/1055040 (16.50%)

FKBP11 act: 57.74 (93.0%ile) | freq: 102870/1055040 (9.75%)

TMEM258 act: 55.01 (92.0%ile) | freq: 245082/1055040 (23.23%)

SPCS3 act: 52.44 (91.0%ile) | freq: 184097/1055040 (17.45%)

SPCS1 act: 50.37 (90.0%ile) | freq: 228479/1055040 (21.66%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=8.35e-04 (13 genes)

OMIM:187900

hpo_diseases p=1.02e-03 (13 genes)

NME3 protein levels

gwas p=3.85e-03 (2 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=1.19e-02 (11 genes)

Spasticity

A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.

hpo_phenotypes p=1.19e-02 (5 genes)

Feature 7761

1,055,040 activations

Top Activating Genes

MORF4L1 act: 63.69 (99.0%ile) | freq: 322911/1055040 (30.61%)

SERBP1 act: 57.86 (98.0%ile) | freq: 225312/1055040 (21.36%)

YWHAE act: 53.99 (97.0%ile) | freq: 291687/1055040 (27.65%)

HNRNPK act: 53.65 (96.0%ile) | freq: 322076/1055040 (30.53%)

PTGES3 act: 52.10 (95.0%ile) | freq: 282047/1055040 (26.73%)

UBE2D3 act: 50.62 (94.0%ile) | freq: 327556/1055040 (31.05%)

YWHAB act: 50.09 (93.0%ile) | freq: 333769/1055040 (31.64%)

CSDE1 act: 49.94 (92.0%ile) | freq: 256627/1055040 (24.32%)

HNRNPC act: 49.29 (91.0%ile) | freq: 303181/1055040 (28.74%)

EIF4G2 act: 49.16 (90.0%ile) | freq: 283128/1055040 (26.84%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=1.35e-04 (16 genes)

Global developmental delay

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

hpo_phenotypes p=1.35e-04 (13 genes)

complex neurodevelopmental disorder

A disorder that involves more than one phenotype associated with the central nervous system, including but not limited to intellectual disability, autism, and seizures (epilepsy).

gencc p=2.27e-04 (4 genes)

ORPHA:231160

hpo_diseases p=3.67e-04 (14 genes)

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=6.51e-04 (12 genes)

Feature 7812

1,055,040 activations

Top Activating Genes

RPL10 act: 93.41 (99.0%ile) | freq: 328609/1055040 (31.15%)

RPS19 act: 91.89 (98.0%ile) | freq: 269876/1055040 (25.58%)

GSTP1 act: 90.18 (97.0%ile) | freq: 52997/1055040 (5.02%)

RPS16 act: 89.55 (96.0%ile) | freq: 90933/1055040 (8.62%)

RPS24 act: 88.99 (95.0%ile) | freq: 286744/1055040 (27.18%)

ATP5F1E act: 88.70 (94.0%ile) | freq: 160412/1055040 (15.20%)

RPS27A act: 88.55 (93.0%ile) | freq: 319387/1055040 (30.27%)

RPL41 act: 88.46 (92.0%ile) | freq: 339255/1055040 (32.16%)

RPS15 act: 88.37 (91.0%ile) | freq: 217667/1055040 (20.63%)

RPL32 act: 88.01 (90.0%ile) | freq: 245501/1055040 (23.27%)

🔬 Biological Validation

Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

gencc p=5.39e-24 (9 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=1.50e-23 (9 genes)

Abnormality of the thenar eminence

An abnormality of the thenar eminence, i.e., of the muscle on the palm of the human hand just beneath the thumb.

hpo_phenotypes p=2.82e-21 (9 genes)

Radial artery aplasia

Congenital absence of the radial artery.

hpo_phenotypes p=2.82e-21 (9 genes)

Elevated red cell adenosine deaminase activity

Increase in the level of adenosine deaminase (ADA), an enzyme involved in purine metabolism, within erythrocytes. ADA is involved in the catabolism of adenosine.

hpo_phenotypes p=2.82e-21 (9 genes)

Feature 8019

1,055,040 activations

Top Activating Genes

RPS12 act: 52.00 (99.0%ile) | freq: 433556/1055040 (41.09%)

TXNDC15 act: 40.98 (98.0%ile) | freq: 10089/1055040 (0.96%)

CFAP300 act: 40.46 (97.0%ile) | freq: 6304/1055040 (0.60%)

FTH1 act: 39.60 (96.0%ile) | freq: 74103/1055040 (7.02%)

ALDOA act: 39.47 (95.0%ile) | freq: 194027/1055040 (18.39%)

OR2M3 act: 38.93 (94.0%ile) | freq: 26697/1055040 (2.53%)

NRP1 act: 38.63 (93.0%ile) | freq: 8560/1055040 (0.81%)

NDUFA6 act: 38.52 (92.0%ile) | freq: 75827/1055040 (7.19%)

CA1 act: 38.40 (91.0%ile) | freq: 5580/1055040 (0.53%)

ENSG00000261826.1 act: 38.06 (90.0%ile) | freq: 13045/1055040 (1.24%)

🔬 Biological Validation

Isolated complex I deficiency

Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome.

orphanet p=5.86e-06 (3 genes)

mitochondrial complex I deficiency

A type of mitochondrial disease charcterized by macrocephaly (large head) with progressive leukodystrophy, encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. The disease is caused by mutations in any of many genes and the inheritance pattern depends on the responsible gene.

gencc p=9.79e-06 (3 genes)

Mitochondrial complex I deficiency

clinvar p=1.74e-05 (2 genes)

Heterotaxy

clinvar p=8.10e-05 (2 genes)

ORPHA:231160

hpo_diseases p=9.52e-05 (14 genes)

Feature 8126

1,055,040 activations

Top Activating Genes

CFL1 act: 68.24 (99.0%ile) | freq: 420176/1055040 (39.83%)

H3-3A act: 66.87 (98.0%ile) | freq: 444913/1055040 (42.17%)

MARCKSL1 act: 62.40 (97.0%ile) | freq: 143459/1055040 (13.60%)

SRP14 act: 50.89 (96.0%ile) | freq: 407625/1055040 (38.64%)

TUBA1A act: 50.67 (95.0%ile) | freq: 245718/1055040 (23.29%)

PAFAH1B3 act: 50.64 (94.0%ile) | freq: 66766/1055040 (6.33%)

TUBB2B act: 50.40 (93.0%ile) | freq: 57656/1055040 (5.46%)

JPT1 act: 50.00 (92.0%ile) | freq: 157310/1055040 (14.91%)

TUBB3 act: 49.91 (91.0%ile) | freq: 10788/1055040 (1.02%)

STMN1 act: 48.38 (90.0%ile) | freq: 145763/1055040 (13.82%)

🔬 Biological Validation

Dysgenesis of the basal ganglia

Structural abnormality of the basal ganglia related to defective development.

hpo_phenotypes p=5.83e-10 (4 genes)

Tubulinopathy-associated dysgyria

A rare genetic central nervous system malformation characterized by dysplasia of the superior cerebellum (especially the vermis), brainstem asymmetry, dysplasia of the basal ganglia, and cortical irregularities with asymmetric abnormalities in gyral size and orientation, as well as varying sulcal depth, but without lissencephaly, pachygyria, or polymicrogyria. Clinically, patients present global developmental delay with motor development usually being more affected that speech. Variable features are abnormal eye movements including oculomotor apraxia, strabismus, seizures, and behavioral problems.

orphanet p=1.82e-09 (3 genes)

tubulinopathy-associated dysgyria

gencc p=3.64e-09 (3 genes)

Congenital fibrosis of extraocular muscles

A rare syndromic disorder with strabismus characterized by congenital non-progressive ophthalmoplegia affecting the oculomotor and/or trochlear nucleus/nerve and their innervated muscles. Patients present with abnormal resting position of the eyes (in most cases infraducted and exotropic), limitation of vertical and horizontal gaze, impaired binocular vision, amblyopia, unilateral or bilateral blepharoptosis, and compensatory abnormal head posture. Extraocular manifestations include intellectual disability, peripheral neuropathy, and skeletal abnormalities, among others.

orphanet p=1.81e-08 (3 genes)

Cerebellar vermis hypoplasia

Underdevelopment of the vermis of cerebellum.

hpo_phenotypes p=3.21e-08 (7 genes)

Feature 8347

1,055,040 activations

Top Activating Genes

BCAP31 act: 51.75 (99.0%ile) | freq: 190134/1055040 (18.02%)

REEP5 act: 48.18 (98.0%ile) | freq: 200338/1055040 (18.99%)

TMCO1 act: 47.91 (97.0%ile) | freq: 162143/1055040 (15.37%)

DAD1 act: 47.66 (96.0%ile) | freq: 222645/1055040 (21.10%)

TMEM59 act: 47.15 (95.0%ile) | freq: 293472/1055040 (27.82%)

LAPTM4A act: 46.55 (94.0%ile) | freq: 200307/1055040 (18.99%)

TMBIM6 act: 45.51 (93.0%ile) | freq: 388282/1055040 (36.80%)

SPCS2 act: 45.45 (92.0%ile) | freq: 236297/1055040 (22.40%)

ATP6V0B act: 45.22 (91.0%ile) | freq: 292829/1055040 (27.76%)

KRTCAP2 act: 44.86 (90.0%ile) | freq: 184815/1055040 (17.52%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=7.51e-04 (12 genes)

ORPHA:231160

hpo_diseases p=2.84e-03 (10 genes)

Curly hair

hpo_phenotypes p=3.21e-02 (2 genes)

Wide mouth

Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).

hpo_phenotypes p=3.48e-02 (3 genes)

Hypermelanotic macule

A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size.

hpo_phenotypes p=3.64e-02 (2 genes)

Feature 8434

1,055,040 activations

Top Activating Genes

S100A14 act: 54.21 (99.0%ile) | freq: 38607/1055040 (3.66%)

FXYD3 act: 49.71 (98.0%ile) | freq: 47540/1055040 (4.51%)

TSPAN1 act: 47.23 (97.0%ile) | freq: 35420/1055040 (3.36%)

C19orf33 act: 45.69 (96.0%ile) | freq: 40273/1055040 (3.82%)

SFN act: 45.65 (95.0%ile) | freq: 22211/1055040 (2.11%)

SFTA2 act: 43.72 (94.0%ile) | freq: 3062/1055040 (0.29%)

CYP4B1 act: 42.97 (93.0%ile) | freq: 15298/1055040 (1.45%)

ENSG00000234985.2 act: 41.67 (92.0%ile) | freq: 5488/1055040 (0.52%)

SLURP2 act: 41.60 (91.0%ile) | freq: 979/1055040 (0.09%)

CLDN3 act: 40.46 (90.0%ile) | freq: 37519/1055040 (3.56%)

🔬 Biological Validation

Diffuse palmoplantar hyperkeratosis

Diffuse abnormal thickening of the skin on the palms and soles.

hpo_phenotypes p=5.80e-07 (3 genes)

Palmoplantar keratoderma

Abnormal thickening of the skin of the palms of the hands and the soles of the feet.

hpo_phenotypes p=7.01e-06 (4 genes)

Erythema

Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.

hpo_phenotypes p=7.01e-06 (4 genes)

Peptic ulcer disease or attention-deficit/hyperactivity disorder (pleiotropy)

gwas p=7.19e-05 (2 genes)

Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)

A carcinoma that arises from epithelial cells of the stomach.

gwas p=2.82e-04 (2 genes)

Feature 8780

1,055,040 activations

Top Activating Genes

SELENOF act: 51.16 (99.0%ile) | freq: 71053/1055040 (6.73%)

ANAPC5 act: 50.68 (98.0%ile) | freq: 100925/1055040 (9.57%)

ANXA7 act: 50.48 (97.0%ile) | freq: 72550/1055040 (6.88%)

IREB2 act: 50.04 (96.0%ile) | freq: 12235/1055040 (1.16%)

AGPS act: 49.80 (95.0%ile) | freq: 18763/1055040 (1.78%)

DNAJB14 act: 49.46 (94.0%ile) | freq: 110367/1055040 (10.46%)

act: 49.42 (93.0%ile) | freq: 496783/1055040 (47.09%)

CYB5R4 act: 49.23 (92.0%ile) | freq: 71760/1055040 (6.80%)

PRR14L act: 49.16 (91.0%ile) | freq: 48438/1055040 (4.59%)

UQCRC2 act: 49.08 (90.0%ile) | freq: 47001/1055040 (4.45%)

🔬 Biological Validation

Global developmental delay

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

hpo_phenotypes p=3.54e-06 (14 genes)

OMIM:187900

hpo_diseases p=3.98e-06 (17 genes)

ORPHA:231160

hpo_diseases p=3.98e-06 (16 genes)

Epicanthus

A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus.

hpo_phenotypes p=6.80e-05 (9 genes)

Microcephaly

Head circumference below 2 standard deviations below the mean for age and gender.

hpo_phenotypes p=6.80e-05 (11 genes)

Feature 9036

1,055,040 activations

Top Activating Genes

PRSS27 act: 65.66 (99.0%ile) | freq: 17871/1055040 (1.69%)

NDRG2 act: 63.50 (98.0%ile) | freq: 80282/1055040 (7.61%)

CNGA1 act: 59.96 (97.0%ile) | freq: 7906/1055040 (0.75%)

TRIP10 act: 56.27 (96.0%ile) | freq: 40352/1055040 (3.82%)

TSPAN6 act: 54.49 (95.0%ile) | freq: 31870/1055040 (3.02%)

ANXA9 act: 52.69 (94.0%ile) | freq: 4212/1055040 (0.40%)

MPRIP act: 51.76 (93.0%ile) | freq: 85293/1055040 (8.08%)

PRSS22 act: 51.48 (92.0%ile) | freq: 24023/1055040 (2.28%)

NECTIN4 act: 50.88 (91.0%ile) | freq: 17674/1055040 (1.68%)

NCCRP1 act: 50.84 (90.0%ile) | freq: 12627/1055040 (1.20%)

🔬 Biological Validation

not provided

clinvar p=3.83e-03 (12 genes)

Patchy alopecia

Transient, non-scarring hair loss and preservation of the hair follicle located in in well-defined patches.

hpo_phenotypes p=4.81e-03 (2 genes)

OMIM:187900

hpo_diseases p=6.38e-03 (11 genes)

ORPHA:231160

hpo_diseases p=1.87e-02 (9 genes)

Sparse eyelashes

Decreased density/number of eyelashes.

hpo_phenotypes p=2.05e-02 (2 genes)

Feature 9593

1,055,040 activations

Top Activating Genes

CTSD act: 65.48 (99.0%ile) | freq: 120192/1055040 (11.39%)

MARCKSL1 act: 65.43 (98.0%ile) | freq: 4550/1055040 (0.43%)

CD55 act: 64.91 (97.0%ile) | freq: 46997/1055040 (4.45%)

CD3E act: 64.70 (96.0%ile) | freq: 1045/1055040 (0.10%)

GAREM1 act: 64.67 (95.0%ile) | freq: 13702/1055040 (1.30%)

AQP9 act: 64.52 (94.0%ile) | freq: 32077/1055040 (3.04%)

RAC2 act: 64.44 (93.0%ile) | freq: 85078/1055040 (8.06%)

ELAPOR2 act: 64.40 (92.0%ile) | freq: 11278/1055040 (1.07%)

ITK act: 64.14 (91.0%ile) | freq: 4859/1055040 (0.46%)

PDE7A act: 64.09 (90.0%ile) | freq: 11535/1055040 (1.09%)

🔬 Biological Validation

Cardiometabolic and hematological traits

gwas p=5.71e-04 (8 genes)

Lymphocyte percentage of white cells

A calculated measurement in which the number of lymphocytes in a specified sample of blood is divided by the total number of white blood cells in the sample, and the result presented as a ratio, fraction, quotient or percentage.

gwas p=6.63e-04 (6 genes)

Myeloid white cell count

gwas p=2.40e-03 (6 genes)

ORPHA:231160

hpo_diseases p=2.61e-03 (13 genes)

OMIM:187900

hpo_diseases p=3.03e-03 (13 genes)

Feature 9762

1,055,040 activations

Top Activating Genes

RPS12 act: 95.18 (99.0%ile) | freq: 510071/1055040 (48.35%)

DYNLT1 act: 64.43 (98.0%ile) | freq: 142616/1055040 (13.52%)

SNX3 act: 55.90 (97.0%ile) | freq: 232610/1055040 (22.05%)

SEC63 act: 52.98 (96.0%ile) | freq: 116869/1055040 (11.08%)

CD164 act: 50.51 (95.0%ile) | freq: 247003/1055040 (23.41%)

PERP act: 49.91 (94.0%ile) | freq: 76565/1055040 (7.26%)

CDC40 act: 48.79 (93.0%ile) | freq: 67608/1055040 (6.41%)

HDAC2 act: 46.30 (92.0%ile) | freq: 104983/1055040 (9.95%)

BCLAF1 act: 46.19 (91.0%ile) | freq: 181431/1055040 (17.20%)

EZR act: 45.51 (90.0%ile) | freq: 191792/1055040 (18.18%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=9.67e-07 (20 genes)

Hippocampal volume

Measurement of the volume of the hippocampus

gwas p=1.91e-03 (3 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=1.99e-03 (15 genes)

ORPHA:231160

hpo_diseases p=2.72e-03 (13 genes)

Axial hypotonia

Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

hpo_phenotypes p=3.77e-03 (5 genes)

Feature 9774

1,055,040 activations

Top Activating Genes

PTPN2 act: 62.51 (99.0%ile) | freq: 138038/1055040 (13.08%)

STAT3 act: 56.85 (98.0%ile) | freq: 185200/1055040 (17.55%)

IFITM2 act: 55.22 (97.0%ile) | freq: 240938/1055040 (22.84%)

NNMT act: 54.11 (96.0%ile) | freq: 42529/1055040 (4.03%)

SBNO2 act: 53.83 (95.0%ile) | freq: 51532/1055040 (4.88%)

IFI16 act: 53.57 (94.0%ile) | freq: 135760/1055040 (12.87%)

OSMR act: 52.24 (93.0%ile) | freq: 24528/1055040 (2.32%)

SOCS3 act: 51.93 (92.0%ile) | freq: 110837/1055040 (10.51%)

IFITM3 act: 51.50 (91.0%ile) | freq: 175407/1055040 (16.63%)

DUSP23 act: 50.36 (90.0%ile) | freq: 71457/1055040 (6.77%)

🔬 Biological Validation

thrombophilia

A condition characterized by an abnormally high level of thrombi. Causes include thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, bone marrow disorders, and antiphospholipid antibody syndrome.

gencc p=1.39e-09 (3 genes)

familial dysfibrinogenemia

Familial dysfibrinogenemia is a coagulation disorder characterized by a bleeding tendency due to a functional anomaly of circulating fibrinogen.

gencc p=1.39e-09 (3 genes)

congenital afibrinogenemia

Familial afibrinogenemia is a coagulation disorder characterized by bleeding symptoms due to a complete absence of circulating fibrinogen.

gencc p=1.39e-09 (3 genes)

Familial hypodysfibrinogenemia

orphanet p=1.39e-09 (3 genes)

Familial dysfibrinogenemia

Familial dysfibrinogenemia is a coagulation disorder characterized by a bleeding tendency due to a functional anomaly of circulating fibrinogen.

orphanet p=1.39e-09 (3 genes)

Feature 9827

1,055,040 activations

Top Activating Genes

RPS8 act: 74.89 (99.0%ile) | freq: 500260/1055040 (47.42%)

RPL15 act: 59.15 (98.0%ile) | freq: 463649/1055040 (43.95%)

S100A11 act: 56.08 (97.0%ile) | freq: 350495/1055040 (33.22%)

CD9 act: 54.68 (96.0%ile) | freq: 157185/1055040 (14.90%)

IGFBP3 act: 51.85 (95.0%ile) | freq: 38358/1055040 (3.64%)

RPL31 act: 45.36 (94.0%ile) | freq: 419370/1055040 (39.75%)

SLPI act: 45.26 (93.0%ile) | freq: 76851/1055040 (7.28%)

ECH1 act: 42.07 (92.0%ile) | freq: 151430/1055040 (14.35%)

RPL35A act: 41.86 (91.0%ile) | freq: 485800/1055040 (46.05%)

HES1 act: 40.56 (90.0%ile) | freq: 75205/1055040 (7.13%)

🔬 Biological Validation

Normochromic anemia

hpo_phenotypes p=1.54e-07 (5 genes)

ORPHA:231160

hpo_diseases p=3.90e-07 (18 genes)

Atrial septal defect

Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.

hpo_phenotypes p=5.78e-06 (8 genes)

Cleft soft palate

Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency.

hpo_phenotypes p=2.10e-05 (4 genes)

OMIM:187900

hpo_diseases p=2.12e-05 (16 genes)

Feature 10141

1,055,040 activations

Top Activating Genes

TLE5 act: 62.82 (99.0%ile) | freq: 198075/1055040 (18.77%)

TMEM123 act: 58.33 (98.0%ile) | freq: 180306/1055040 (17.09%)

GSTK1 act: 49.77 (97.0%ile) | freq: 170169/1055040 (16.13%)

NOSIP act: 47.74 (96.0%ile) | freq: 128517/1055040 (12.18%)

HINT1 act: 47.08 (95.0%ile) | freq: 370977/1055040 (35.16%)

UXT act: 45.54 (94.0%ile) | freq: 189063/1055040 (17.92%)

C12orf57 act: 43.14 (93.0%ile) | freq: 204199/1055040 (19.35%)

GPSM3 act: 42.67 (92.0%ile) | freq: 148931/1055040 (14.12%)

COMMD6 act: 41.58 (91.0%ile) | freq: 281674/1055040 (26.70%)

LEPROTL1 act: 40.85 (90.0%ile) | freq: 125229/1055040 (11.87%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=4.25e-03 (11 genes)

Seizure

clinvar p=1.35e-02 (2 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=3.95e-02 (8 genes)

Infantile onset

Onset of signs or symptoms of disease between 28 days to one year of life.

hpo_phenotypes p=3.95e-02 (5 genes)

Increased CSF lactate

Increased concentration of lactate in the cerebrospinal fluid.

hpo_phenotypes p=3.95e-02 (2 genes)

Feature 10159

1,055,040 activations

Top Activating Genes

CETN2 act: 70.92 (99.0%ile) | freq: 58636/1055040 (5.56%)

MORN2 act: 70.26 (98.0%ile) | freq: 30545/1055040 (2.90%)

PIFO act: 69.37 (97.0%ile) | freq: 7431/1055040 (0.70%)

IFT22 act: 69.36 (96.0%ile) | freq: 42874/1055040 (4.06%)

DNALI1 act: 69.05 (95.0%ile) | freq: 18921/1055040 (1.79%)

RSPH1 act: 68.25 (94.0%ile) | freq: 14722/1055040 (1.40%)

PIERCE1 act: 68.06 (93.0%ile) | freq: 9813/1055040 (0.93%)

ZMYND10 act: 67.46 (92.0%ile) | freq: 8269/1055040 (0.78%)

OSCP1 act: 66.56 (91.0%ile) | freq: 11246/1055040 (1.07%)

SPA17 act: 63.80 (90.0%ile) | freq: 16203/1055040 (1.54%)

🔬 Biological Validation

Situs inversus totalis

A left-right reversal (or mirror reflection) of the anatomical location of the major thoracic and abdominal organs.

hpo_phenotypes p=1.00e-24 (14 genes)

Asplenia

Absence (aplasia) of the spleen.

hpo_phenotypes p=1.13e-19 (11 genes)

Chronic sinusitis

A chronic form of sinusitis.

hpo_phenotypes p=7.63e-19 (10 genes)

Primary ciliary dyskinesia

A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of the patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy).

orphanet p=1.69e-16 (8 genes)

primary ciliary dyskinesia

A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of PCD patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy).

gencc p=3.31e-16 (8 genes)

Feature 10257

1,055,040 activations

Top Activating Genes

CTSC act: 69.52 (99.0%ile) | freq: 145723/1055040 (13.81%)

PLEKHS1 act: 59.61 (98.0%ile) | freq: 12521/1055040 (1.19%)

CYP2F1 act: 58.63 (97.0%ile) | freq: 9425/1055040 (0.89%)

PRSS23 act: 58.15 (96.0%ile) | freq: 55983/1055040 (5.31%)

CYP2A13 act: 56.78 (95.0%ile) | freq: 1227/1055040 (0.12%)

SLC31A1 act: 56.39 (94.0%ile) | freq: 49191/1055040 (4.66%)

CYP2J2 act: 56.11 (93.0%ile) | freq: 13770/1055040 (1.31%)

NHERF1 act: 54.95 (92.0%ile) | freq: 96916/1055040 (9.19%)

CAPN13 act: 54.37 (91.0%ile) | freq: 7917/1055040 (0.75%)

HEY1 act: 54.13 (90.0%ile) | freq: 22627/1055040 (2.14%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=2.11e-03 (11 genes)

ORPHA:231160

hpo_diseases p=2.11e-03 (10 genes)

neurodevelopmental disorder

A behavioral and cognitive disorder with onset during the developmental period that involves impaired or aberrant development of intellectual, motor, or social functions.

gencc p=6.33e-03 (2 genes)

Hyperphosphaturia

An increased excretion of phosphates in the urine.

hpo_phenotypes p=9.73e-03 (2 genes)

Pustule

A small elevation of the skin containing cloudy or purulent material usually consisting of necrotic inflammatory cells.

hpo_phenotypes p=9.73e-03 (2 genes)

Feature 10856

1,055,040 activations

Top Activating Genes

HINT1 act: 89.77 (99.0%ile) | freq: 370977/1055040 (35.16%)

FXYD3 act: 78.73 (98.0%ile) | freq: 47540/1055040 (4.51%)

SPINT2 act: 49.05 (97.0%ile) | freq: 141543/1055040 (13.42%)

S100A14 act: 45.61 (96.0%ile) | freq: 38607/1055040 (3.66%)

BSG act: 45.47 (95.0%ile) | freq: 232958/1055040 (22.08%)

NPC2 act: 45.08 (94.0%ile) | freq: 223830/1055040 (21.22%)

ELF3 act: 43.98 (93.0%ile) | freq: 76612/1055040 (7.26%)

AGR2 act: 41.25 (92.0%ile) | freq: 47795/1055040 (4.53%)

IGFBP3 act: 41.22 (91.0%ile) | freq: 38358/1055040 (3.64%)

ADIRF act: 39.97 (90.0%ile) | freq: 61808/1055040 (5.86%)

🔬 Biological Validation

Narcolepsy type 2

A rare neurologic disease characterized by excessive daytime sleepiness associated with uncontrollable sleep urges and sometimes sleep paralysis, and hypnagogic/hypnopompic hallucinations.

orphanet p=7.21e-06 (2 genes)

Cough

A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.

hpo_phenotypes p=9.53e-06 (5 genes)

Granulomatosis with polyangiitis

A rare anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis characterized by necrotizing inflammation of small and medium vessels (capillaries, venules and arterioles), resulting in tissue ischemia.

orphanet p=1.20e-05 (2 genes)

Cataplexy

A sudden and transient episode of bilateral loss of muscle tone, often triggered by emotions.

hpo_phenotypes p=1.53e-05 (3 genes)

Narcolepsy type 1

A rare neurologic disease characterized by excessive daytime sleepiness associated with uncontrollable sleep urges and cataplexy (sudden loss of muscle tone while awake, often triggered by pleasant emotions).

orphanet p=2.24e-05 (2 genes)

Feature 11061

1,055,040 activations

Top Activating Genes

RAB13 act: 47.25 (99.0%ile) | freq: 99708/1055040 (9.45%)

TPM2 act: 46.59 (98.0%ile) | freq: 26587/1055040 (2.52%)

DMKN act: 46.27 (97.0%ile) | freq: 33868/1055040 (3.21%)

PLP2 act: 42.95 (96.0%ile) | freq: 141107/1055040 (13.37%)

WFDC2 act: 41.81 (95.0%ile) | freq: 82513/1055040 (7.82%)

PERP act: 41.53 (94.0%ile) | freq: 76565/1055040 (7.26%)

PHLDA2 act: 40.23 (93.0%ile) | freq: 57969/1055040 (5.49%)

IGFBP3 act: 40.07 (92.0%ile) | freq: 38358/1055040 (3.64%)

TMEM45A act: 39.76 (91.0%ile) | freq: 43311/1055040 (4.11%)

IFI27L2 act: 38.54 (90.0%ile) | freq: 116672/1055040 (11.06%)

🔬 Biological Validation

Neoplasm

clinvar p=3.00e-05 (2 genes)

Weight loss

Reduction of total body weight.

hpo_phenotypes p=3.62e-05 (6 genes)

Osteolysis

Osteolysis refers to the destruction of bone through bone resorption with removal or loss of calcium.

hpo_phenotypes p=3.62e-05 (4 genes)

Pruritus

Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.

hpo_phenotypes p=3.11e-04 (4 genes)

OMIM:187900

hpo_diseases p=1.63e-03 (12 genes)

Feature 11445

1,055,040 activations

Top Activating Genes

act: 351.52 (99.0%ile) | freq: 1054603/1055040 (99.96%)

SIK3 act: 283.58 (98.0%ile) | freq: 29582/1055040 (2.80%)

TCF4 act: 281.83 (97.0%ile) | freq: 36024/1055040 (3.41%)

SAMD12 act: 277.89 (96.0%ile) | freq: 26330/1055040 (2.50%)

SARAF act: 277.60 (95.0%ile) | freq: 22431/1055040 (2.13%)

SGK1 act: 274.39 (94.0%ile) | freq: 43610/1055040 (4.13%)

RASAL2 act: 273.66 (93.0%ile) | freq: 19168/1055040 (1.82%)

TJP1 act: 272.14 (92.0%ile) | freq: 16747/1055040 (1.59%)

GABRB2 act: 271.63 (91.0%ile) | freq: 14224/1055040 (1.35%)

CNTN1 act: 271.52 (90.0%ile) | freq: 16064/1055040 (1.52%)

🔬 Biological Validation

Cognitive ability (MTAG)

A measure of educational progress reported using a questionnaire based approach, often used as a proxy for cognitive performance as the two are correlated.

gwas p=1.59e-04 (9 genes)

arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease that consists in progressive dystrophy of primarily the right ventricular myocardium with fibro-fatty replacement and ventricular dilation, and that is clinically characterized by ventricular arrhythmias and a risk of sudden cardiac death.

gencc p=7.76e-04 (2 genes)

autosomal dominant non-syndromic intellectual disability

Autosomal dominant form of non-syndromic intellectual disability.

gencc p=9.32e-04 (2 genes)

Sleep duration

gwas p=1.04e-03 (4 genes)

Protein quantitative trait loci (liver)

Is a quantification of some protein, typically obtained from an individual with the intention of using the measurement in some diagnostic process.

gwas p=1.26e-03 (10 genes)

Feature 11455

1,055,040 activations

Top Activating Genes

HNRNPF act: 53.46 (99.0%ile) | freq: 196471/1055040 (18.62%)

FADD act: 50.74 (98.0%ile) | freq: 19942/1055040 (1.89%)

RRS1 act: 50.53 (97.0%ile) | freq: 21928/1055040 (2.08%)

NOP16 act: 49.29 (96.0%ile) | freq: 35004/1055040 (3.32%)

RPP38 act: 48.65 (95.0%ile) | freq: 17863/1055040 (1.69%)

ZNHIT2 act: 47.52 (94.0%ile) | freq: 20141/1055040 (1.91%)

IMP3 act: 47.21 (93.0%ile) | freq: 109462/1055040 (10.38%)

C14orf119 act: 46.93 (92.0%ile) | freq: 79041/1055040 (7.49%)

PPAN act: 46.05 (91.0%ile) | freq: 29083/1055040 (2.76%)

NCBP2AS2 act: 45.90 (90.0%ile) | freq: 47950/1055040 (4.54%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=1.94e-07 (16 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=3.00e-07 (16 genes)

OMIM:187900

hpo_diseases p=3.54e-07 (16 genes)

Global developmental delay

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

hpo_phenotypes p=4.58e-05 (11 genes)

Cerebral atrophy

Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.

hpo_phenotypes p=4.58e-05 (6 genes)

Feature 11701

1,055,040 activations

Top Activating Genes

MRPL54 act: 55.39 (99.0%ile) | freq: 118910/1055040 (11.27%)

RBM3 act: 54.18 (98.0%ile) | freq: 226214/1055040 (21.44%)

CIRBP act: 54.01 (97.0%ile) | freq: 324929/1055040 (30.80%)

CHMP3 act: 49.36 (96.0%ile) | freq: 113172/1055040 (10.73%)

PMF1 act: 48.77 (95.0%ile) | freq: 67269/1055040 (6.38%)

EID1 act: 47.70 (94.0%ile) | freq: 219209/1055040 (20.78%)

SMDT1 act: 47.00 (93.0%ile) | freq: 190102/1055040 (18.02%)

ENSA act: 45.64 (92.0%ile) | freq: 151842/1055040 (14.39%)

TIMM8B act: 43.68 (91.0%ile) | freq: 130154/1055040 (12.34%)

SPAG7 act: 42.23 (90.0%ile) | freq: 111363/1055040 (10.56%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=7.51e-04 (12 genes)

Axial hypotonia

Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

hpo_phenotypes p=2.53e-03 (4 genes)

Infantile onset

Onset of signs or symptoms of disease between 28 days to one year of life.

hpo_phenotypes p=2.53e-03 (7 genes)

Optic atrophy

Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

hpo_phenotypes p=2.53e-03 (5 genes)

neurodevelopmental disorder

A behavioral and cognitive disorder with onset during the developmental period that involves impaired or aberrant development of intellectual, motor, or social functions.

gencc p=1.36e-02 (2 genes)

Feature 11860

1,055,040 activations

Top Activating Genes

TUBGCP5 act: 63.06 (99.0%ile) | freq: 2642/1055040 (0.25%)

RPL32 act: 61.20 (98.0%ile) | freq: 252160/1055040 (23.90%)

RPL34 act: 60.74 (97.0%ile) | freq: 266513/1055040 (25.26%)

TRMT1L act: 59.50 (96.0%ile) | freq: 1860/1055040 (0.18%)

GTF3C1 act: 58.92 (95.0%ile) | freq: 57/1055040 (0.01%)

DPP8 act: 58.49 (94.0%ile) | freq: 1750/1055040 (0.17%)

RPS12 act: 58.38 (93.0%ile) | freq: 278629/1055040 (26.41%)

TMX3 act: 58.34 (92.0%ile) | freq: 8102/1055040 (0.77%)

ENSA act: 58.33 (91.0%ile) | freq: 8067/1055040 (0.76%)

ZNF714 act: 58.25 (90.0%ile) | freq: 1446/1055040 (0.14%)

🔬 Biological Validation

Short stature

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

hpo_phenotypes p=4.82e-09 (14 genes)

Developmental cataract

A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens.

hpo_phenotypes p=2.82e-08 (7 genes)

Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

gencc p=3.43e-08 (4 genes)

Reduced contrast sensitivity

An abnormality in perception of contrast. Spatial contrast is a physical dimension referring to the light-dark transition of a border or an edge in an image that delineates the existence of a pattern or an object. Contrast sensitivity refers to a measure of how much contrast a person requires to see a target. Contrast-sensitivity measurements differ from acuity measurements; acuity is a measure of the spatial-resolving ability of the visual system under conditions of very high contrast, whereas contrast sensitivity is a measure of the threshold contrast for seeing a target.

hpo_phenotypes p=3.54e-08 (4 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=3.62e-08 (4 genes)

Feature 11879

1,055,040 activations

Top Activating Genes

ID3 act: 74.26 (99.0%ile) | freq: 68878/1055040 (6.53%)

ID1 act: 69.13 (98.0%ile) | freq: 59732/1055040 (5.66%)

CFL1 act: 67.00 (97.0%ile) | freq: 420176/1055040 (39.83%)

ENO1 act: 66.95 (96.0%ile) | freq: 323548/1055040 (30.67%)

HES1 act: 62.94 (95.0%ile) | freq: 75207/1055040 (7.13%)

ID2 act: 62.40 (94.0%ile) | freq: 181692/1055040 (17.22%)

NDUFA4 act: 60.93 (93.0%ile) | freq: 338850/1055040 (32.12%)

LDHA act: 59.41 (92.0%ile) | freq: 275653/1055040 (26.13%)

PKM act: 51.97 (91.0%ile) | freq: 290267/1055040 (27.51%)

ALDH3A1 act: 51.01 (90.0%ile) | freq: 12582/1055040 (1.19%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=5.74e-05 (15 genes)

Cholelithiasis

Hard, pebble-like deposits that form within the gallbladder.

hpo_phenotypes p=9.06e-05 (4 genes)

Cholecystitis

The presence of inflammatory changes in the gallbladder.

hpo_phenotypes p=9.06e-05 (3 genes)

ORPHA:231160

hpo_diseases p=2.16e-04 (13 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=5.11e-04 (13 genes)

Feature 11913

1,055,040 activations

Top Activating Genes

VAMP2 act: 48.46 (99.0%ile) | freq: 231754/1055040 (21.97%)

CALM3 act: 47.16 (98.0%ile) | freq: 218511/1055040 (20.71%)

ATP6V0C act: 41.78 (97.0%ile) | freq: 62615/1055040 (5.93%)

UQCRH act: 41.76 (96.0%ile) | freq: 284887/1055040 (27.00%)

PREPL act: 41.15 (95.0%ile) | freq: 92607/1055040 (8.78%)

PRDX5 act: 41.11 (94.0%ile) | freq: 236590/1055040 (22.42%)

RAB3A act: 39.43 (93.0%ile) | freq: 52979/1055040 (5.02%)

TMEM59L act: 39.03 (92.0%ile) | freq: 41865/1055040 (3.97%)

ARF3 act: 38.59 (91.0%ile) | freq: 75308/1055040 (7.14%)

NAP1L5 act: 38.49 (90.0%ile) | freq: 27638/1055040 (2.62%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=9.93e-09 (21 genes)

ORPHA:231160

hpo_diseases p=3.25e-07 (18 genes)

Myoclonic seizure

A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.

hpo_phenotypes p=1.70e-06 (6 genes)

Epileptic spasm

A sudden flexion, extension, or mixed extension-flexion of predominantly proximal and truncal muscles that is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure. Limited forms may occur: Grimacing, head nodding, or subtle eye movements. Epileptic spasms frequently occur in clusters. Infantile spasms are the best known form, but spasms can occur at all ages

hpo_phenotypes p=1.77e-06 (5 genes)

Global developmental delay

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

hpo_phenotypes p=1.80e-06 (14 genes)

Feature 12570

1,055,040 activations

Top Activating Genes

RPLP1 act: 69.51 (99.0%ile) | freq: 599989/1055040 (56.87%)

S100A6 act: 62.45 (98.0%ile) | freq: 428024/1055040 (40.57%)

GAPDH act: 62.12 (97.0%ile) | freq: 526366/1055040 (49.89%)

B2M act: 60.72 (96.0%ile) | freq: 571952/1055040 (54.21%)

RPLP0 act: 60.55 (95.0%ile) | freq: 420212/1055040 (39.83%)

RPL41 act: 59.47 (94.0%ile) | freq: 535560/1055040 (50.76%)

MALAT1 act: 58.07 (93.0%ile) | freq: 579387/1055040 (54.92%)

CD74 act: 57.91 (92.0%ile) | freq: 282998/1055040 (26.82%)

RPL13A act: 57.83 (91.0%ile) | freq: 486062/1055040 (46.07%)

FTH1 act: 56.86 (90.0%ile) | freq: 613773/1055040 (58.18%)

🔬 Biological Validation

Reduced contrast sensitivity

An abnormality in perception of contrast. Spatial contrast is a physical dimension referring to the light-dark transition of a border or an edge in an image that delineates the existence of a pattern or an object. Contrast sensitivity refers to a measure of how much contrast a person requires to see a target. Contrast-sensitivity measurements differ from acuity measurements; acuity is a measure of the spatial-resolving ability of the visual system under conditions of very high contrast, whereas contrast sensitivity is a measure of the threshold contrast for seeing a target.

hpo_phenotypes p=4.59e-14 (6 genes)

Ventricular preexcitation

An abnormality in which the cardiac ventricles depolarize too early as a result of an abnormality of cardiac conduction pathways such as an accessory pathway.

hpo_phenotypes p=4.59e-14 (6 genes)

Centrocecal scotoma

A scotoma (area of diminished vision within the visual field) located between the central point of fixation and the blind spot with a roughly horizontal oval shape.

hpo_phenotypes p=4.59e-14 (6 genes)

Leber hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON) is a mitochondrial neurodegenerative disease affecting the optic nerve and often characterized by sudden vision loss in young adult carriers.

gencc p=5.73e-13 (5 genes)

mitochondrial disease

gencc p=5.73e-13 (8 genes)

Feature 12828

1,055,040 activations

Top Activating Genes

CCNL2 act: 70.79 (99.0%ile) | freq: 110855/1055040 (10.51%)

CFAP100 act: 64.57 (98.0%ile) | freq: 3194/1055040 (0.30%)

MST1 act: 64.10 (97.0%ile) | freq: 31341/1055040 (2.97%)

PGGHG act: 64.02 (96.0%ile) | freq: 29454/1055040 (2.79%)

TCIRG1 act: 63.25 (95.0%ile) | freq: 88755/1055040 (8.41%)

KIFC2 act: 62.18 (94.0%ile) | freq: 20266/1055040 (1.92%)

DNAH1 act: 61.90 (93.0%ile) | freq: 11301/1055040 (1.07%)

ACADVL act: 61.11 (92.0%ile) | freq: 165047/1055040 (15.64%)

MAPK15 act: 60.59 (91.0%ile) | freq: 3203/1055040 (0.30%)

PABPC1L act: 60.55 (90.0%ile) | freq: 13424/1055040 (1.27%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=2.70e-04 (15 genes)

Primary ciliary dyskinesia

A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of the patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy).

orphanet p=1.38e-03 (2 genes)

primary ciliary dyskinesia

A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of PCD patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy).

gencc p=1.61e-03 (2 genes)

ORPHA:231160

hpo_diseases p=2.61e-03 (12 genes)

Chronic rhinitis

Chronic inflammation of the nasal mucosa.

hpo_phenotypes p=3.27e-03 (3 genes)

Feature 12874

1,055,040 activations

Top Activating Genes

CLIC1 act: 57.55 (99.0%ile) | freq: 291089/1055040 (27.59%)

BAG6 act: 55.80 (98.0%ile) | freq: 89094/1055040 (8.44%)

MRPL14 act: 53.87 (97.0%ile) | freq: 112493/1055040 (10.66%)

SRPK1 act: 51.87 (96.0%ile) | freq: 70405/1055040 (6.67%)

ABCF1 act: 50.97 (95.0%ile) | freq: 100258/1055040 (9.50%)

RPL7L1 act: 50.28 (94.0%ile) | freq: 111202/1055040 (10.54%)

CUTA act: 49.84 (93.0%ile) | freq: 209965/1055040 (19.90%)

PRRC2A act: 49.49 (92.0%ile) | freq: 80874/1055040 (7.67%)

CDC5L act: 48.72 (91.0%ile) | freq: 59225/1055040 (5.61%)

MTCH1 act: 48.54 (90.0%ile) | freq: 186256/1055040 (17.65%)

🔬 Biological Validation

Menopause (age at onset)

The age of onset of (human) menopause, the beginning of the first menstrual cycle in an individual

gwas p=1.56e-02 (2 genes)

Superior parietal area (unadjusted for global measures)

gwas p=1.56e-02 (3 genes)

Mosaic loss of chromosome Y (Y chromosome dosage)

gwas p=1.56e-02 (2 genes)

Feature 13078

1,055,040 activations

Top Activating Genes

CHD8 act: 36.61 (99.0%ile) | freq: 83863/1055040 (7.95%)

MGA act: 36.22 (98.0%ile) | freq: 59606/1055040 (5.65%)

XPO4 act: 35.88 (97.0%ile) | freq: 48186/1055040 (4.57%)

SUPT6H act: 35.71 (96.0%ile) | freq: 52637/1055040 (4.99%)

HEATR5B act: 35.65 (95.0%ile) | freq: 31958/1055040 (3.03%)

EP400 act: 35.41 (94.0%ile) | freq: 45563/1055040 (4.32%)

DIDO1 act: 35.21 (93.0%ile) | freq: 63507/1055040 (6.02%)

HEATR1 act: 35.00 (92.0%ile) | freq: 23984/1055040 (2.27%)

ZDHHC17 act: 34.56 (91.0%ile) | freq: 34193/1055040 (3.24%)

NUP160 act: 34.49 (90.0%ile) | freq: 49200/1055040 (4.66%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=3.16e-06 (19 genes)

Intellectual disability

clinvar p=5.26e-06 (8 genes)

ORPHA:231160

hpo_diseases p=1.77e-04 (15 genes)

Thin upper lip vermilion

Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).

hpo_phenotypes p=4.81e-04 (6 genes)

Obesity

Accumulation of substantial excess body fat.

hpo_phenotypes p=4.81e-04 (6 genes)

Feature 13429

1,055,040 activations

Top Activating Genes

AP1S1 act: 80.73 (99.0%ile) | freq: 610/1055040 (0.06%)

MBD3 act: 80.39 (98.0%ile) | freq: 1430/1055040 (0.14%)

MRPL46 act: 78.22 (97.0%ile) | freq: 910/1055040 (0.09%)

ATP5PB act: 78.06 (96.0%ile) | freq: 3380/1055040 (0.32%)

AIMP2 act: 77.77 (95.0%ile) | freq: 810/1055040 (0.08%)

NDUFA8 act: 77.39 (94.0%ile) | freq: 5090/1055040 (0.48%)

TMEM126A act: 77.23 (93.0%ile) | freq: 2967/1055040 (0.28%)

ASB1 act: 76.83 (92.0%ile) | freq: 560/1055040 (0.05%)

FBXO2 act: 76.81 (91.0%ile) | freq: 450/1055040 (0.04%)

ZNF570 act: 76.79 (90.0%ile) | freq: 280/1055040 (0.03%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=3.09e-03 (11 genes)

PILRB protein levels

gwas p=6.39e-03 (2 genes)

PILRA protein levels

Quantification of paired immunoglobulin-like type 2 receptor alpha in a sample.

gwas p=6.39e-03 (2 genes)

Autosomal recessive inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).

hpo_phenotypes p=1.82e-02 (9 genes)

Peripheral neuropathy

Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.

hpo_phenotypes p=1.82e-02 (3 genes)

Feature 13794

1,055,040 activations

Top Activating Genes

ANXA2 act: 70.67 (99.0%ile) | freq: 267684/1055040 (25.37%)

SLPI act: 60.27 (98.0%ile) | freq: 76851/1055040 (7.28%)

NPC2 act: 59.09 (97.0%ile) | freq: 223830/1055040 (21.22%)

HLA-DMA act: 51.63 (96.0%ile) | freq: 83242/1055040 (7.89%)

SUB1 act: 47.37 (95.0%ile) | freq: 309840/1055040 (29.37%)

TIMP1 act: 46.61 (94.0%ile) | freq: 247806/1055040 (23.49%)

RPL12 act: 46.43 (93.0%ile) | freq: 469609/1055040 (44.51%)

HLA-DPB1 act: 43.76 (92.0%ile) | freq: 159009/1055040 (15.07%)

ARL6IP5 act: 43.73 (91.0%ile) | freq: 245991/1055040 (23.32%)

HLA-DQB1 act: 42.80 (90.0%ile) | freq: 83868/1055040 (7.95%)

🔬 Biological Validation

Cataplexy

A sudden and transient episode of bilateral loss of muscle tone, often triggered by emotions.

hpo_phenotypes p=9.41e-08 (4 genes)

Arthralgia

Joint pain.

hpo_phenotypes p=1.10e-07 (7 genes)

Narcolepsy type 1

A rare neurologic disease characterized by excessive daytime sleepiness associated with uncontrollable sleep urges and cataplexy (sudden loss of muscle tone while awake, often triggered by pleasant emotions).

orphanet p=2.03e-07 (3 genes)

Pulmonary fibrosis

Replacement of normal lung tissues by fibroblasts and collagen.

hpo_phenotypes p=1.20e-06 (5 genes)

Narcolepsy type 2

A rare neurologic disease characterized by excessive daytime sleepiness associated with uncontrollable sleep urges and sometimes sleep paralysis, and hypnagogic/hypnopompic hallucinations.

orphanet p=5.80e-06 (2 genes)

Feature 13947

1,055,040 activations

Top Activating Genes

SLPI act: 84.39 (99.0%ile) | freq: 45841/1055040 (4.34%)

S100A9 act: 84.33 (98.0%ile) | freq: 153250/1055040 (14.53%)

RPS27A act: 82.14 (97.0%ile) | freq: 260302/1055040 (24.67%)

KCND2 act: 80.30 (96.0%ile) | freq: 15214/1055040 (1.44%)

MT-CO3 act: 79.97 (95.0%ile) | freq: 379623/1055040 (35.98%)

SERPINA1 act: 78.66 (94.0%ile) | freq: 57724/1055040 (5.47%)

ERBB4 act: 78.43 (93.0%ile) | freq: 39399/1055040 (3.73%)

GRID2 act: 76.31 (92.0%ile) | freq: 9272/1055040 (0.88%)

DST act: 76.26 (91.0%ile) | freq: 78321/1055040 (7.42%)

CCL20 act: 76.07 (90.0%ile) | freq: 75204/1055040 (7.13%)

🔬 Biological Validation

Developmental cataract

A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens.

hpo_phenotypes p=4.86e-06 (6 genes)

Mitochondrial disease

clinvar p=8.65e-06 (3 genes)

Abnormal aortic valve physiology

clinvar p=1.09e-05 (2 genes)

ORPHA:231160

hpo_diseases p=2.95e-05 (16 genes)

OMIM:187900

hpo_diseases p=4.76e-05 (16 genes)

Feature 14187

1,055,040 activations

Top Activating Genes

CCL20 act: 67.15 (99.0%ile) | freq: 81907/1055040 (7.76%)

CYB5A act: 56.76 (98.0%ile) | freq: 155725/1055040 (14.76%)

RPL3 act: 49.39 (97.0%ile) | freq: 478668/1055040 (45.37%)

IGFBP3 act: 45.63 (96.0%ile) | freq: 38358/1055040 (3.64%)

HILPDA act: 44.05 (95.0%ile) | freq: 27019/1055040 (2.56%)

SPINT2 act: 41.75 (94.0%ile) | freq: 141543/1055040 (13.42%)

IGFBP5 act: 41.38 (93.0%ile) | freq: 41037/1055040 (3.89%)

ERRFI1 act: 39.58 (92.0%ile) | freq: 49729/1055040 (4.71%)

AQP3 act: 38.42 (91.0%ile) | freq: 75772/1055040 (7.18%)

SDC4 act: 38.34 (90.0%ile) | freq: 90120/1055040 (8.54%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=5.36e-04 (13 genes)

ORPHA:231160

hpo_diseases p=1.82e-03 (11 genes)

Prostate cancer

A carcinoma that arises from epithelial cells of the prostate gland.

gwas p=2.81e-03 (4 genes)

Dysarthria

Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.

hpo_phenotypes p=5.37e-03 (5 genes)

Sparse eyebrow

Decreased density/number of eyebrow hairs.

hpo_phenotypes p=5.37e-03 (3 genes)

Feature 14243

1,055,040 activations

Top Activating Genes

NPM1 act: 78.03 (99.0%ile) | freq: 344801/1055040 (32.68%)

EIF4A1 act: 64.35 (98.0%ile) | freq: 140303/1055040 (13.30%)

HINT1 act: 64.23 (97.0%ile) | freq: 370977/1055040 (35.16%)

HSP90AB1 act: 56.30 (96.0%ile) | freq: 427863/1055040 (40.55%)

RAN act: 54.81 (95.0%ile) | freq: 245678/1055040 (23.29%)

YBX1 act: 54.16 (94.0%ile) | freq: 369518/1055040 (35.02%)

HSPA8 act: 51.01 (93.0%ile) | freq: 325711/1055040 (30.87%)

CHCHD2 act: 49.17 (92.0%ile) | freq: 363969/1055040 (34.50%)

BTF3 act: 48.57 (91.0%ile) | freq: 361358/1055040 (34.25%)

SLC25A5 act: 48.24 (90.0%ile) | freq: 238363/1055040 (22.59%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=1.24e-07 (20 genes)

ORPHA:231160

hpo_diseases p=5.29e-07 (18 genes)

Inclusion body myopathy with Paget disease of bone and frontotemporal dementia

Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative genetic disorder characterized by adult-onset proximal and distal muscle weakness (clinically resembling limb-girdle muscular dystrophy); early-onset Paget disease of bone, manifesting with bone pain, deformity and enlargement of the long-bones; and premature frontotemporal dementia, manifesting first with dysnomia, dyscalculia and comprehension deficits followed by progressive aphasia, alexia, and agraphia. As the disease progresses, muscle weakness begins to affect the other limbs and respiratory muscles, ultimately resulting in respiratory or cardiac failure.

orphanet p=7.66e-06 (2 genes)

inclusion body myopathy with Paget disease of bone and frontotemporal dementia

Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative genetic disorder characterized by adult-onset proximal and distal muscle weakness (clinically resembling limb-girdle muscular dystrophy); early-onset Paget disease of bone, manifesting with bone pain, deformity and enlargement of the long-bones; and premature frontotemporal dementia, manifesting first with dysnomia, dyscalculia and comprehension deficits followed by progressive aphasia, alexia, and agraphia. As the disease progresses, muscle weakness begins to affect the other limbs and respiratory muscles, ultimately resulting in respiratory or cardiac failure.

gencc p=1.15e-05 (2 genes)

amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord.

gencc p=2.49e-05 (3 genes)

Feature 14400

1,055,040 activations

Top Activating Genes

ZFP36L1 act: 56.96 (99.0%ile) | freq: 259966/1055040 (24.64%)

CYP2B7P_ENSG00000256612 act: 54.91 (98.0%ile) | freq: 4267/1055040 (0.40%)

SRI act: 52.05 (97.0%ile) | freq: 168289/1055040 (15.95%)

SLC34A2 act: 49.67 (96.0%ile) | freq: 20933/1055040 (1.98%)

CXCL17 act: 48.26 (95.0%ile) | freq: 29815/1055040 (2.83%)

CYB5A act: 46.96 (94.0%ile) | freq: 151640/1055040 (14.37%)

NKX2-1 act: 46.82 (93.0%ile) | freq: 3728/1055040 (0.35%)

SFTPB act: 46.05 (92.0%ile) | freq: 8518/1055040 (0.81%)

TMEM45A act: 45.10 (91.0%ile) | freq: 43216/1055040 (4.10%)

HMGB3 act: 44.83 (90.0%ile) | freq: 37226/1055040 (3.53%)

🔬 Biological Validation

Ground-glass opacification

On chest radiographs, ground-glass opacity appears as an area of hazy increased lung opacity, usually extensive, within which margins of pulmonary vessels may be indistinct. On CT scans, it appears as hazy increased opacity of lung, with preservation of bronchial and vascular margins. It is caused by partial filling of airspaces, interstitial thickening (due to fluid, cells, and/or fibrosis), partial collapse of alveoli, increased capillary blood volume, or a combination of these, the common factor being the partial displacement of air. Ground-glass opacity is less opaque than consolidation, in which bronchovascular margins are obscured.

hpo_phenotypes p=6.82e-07 (4 genes)

Interlobular septal thickening

Presence of thickening of the interlobular septa of the lungs as seen on a CT scan.

hpo_phenotypes p=6.82e-07 (3 genes)

Oxygen desaturation on exertion

Oxygen saturation less than 95% on exertion or arterial partial pressure of oxygen falling by more than 1kPa.

hpo_phenotypes p=2.67e-05 (2 genes)

ORPHA:231160

hpo_diseases p=2.12e-04 (13 genes)

OMIM:612278

hpo_diseases p=1.28e-03 (4 genes)

Feature 14488

1,055,040 activations

Top Activating Genes

UBL5 act: 62.33 (99.0%ile) | freq: 309165/1055040 (29.30%)

COX6B1 act: 62.07 (98.0%ile) | freq: 313488/1055040 (29.71%)

ELOB act: 60.55 (97.0%ile) | freq: 288640/1055040 (27.36%)

COX7A2 act: 60.43 (96.0%ile) | freq: 309940/1055040 (29.38%)

RPL36AL act: 60.31 (95.0%ile) | freq: 264692/1055040 (25.09%)

TRMT112 act: 59.97 (94.0%ile) | freq: 170567/1055040 (16.17%)

COX7B act: 59.37 (93.0%ile) | freq: 260666/1055040 (24.71%)

HCST act: 59.37 (92.0%ile) | freq: 92772/1055040 (8.79%)

POMP act: 58.91 (91.0%ile) | freq: 164702/1055040 (15.61%)

ATP5MF act: 58.85 (90.0%ile) | freq: 207661/1055040 (19.68%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=1.78e-09 (18 genes)

Hepatomegaly

Abnormally increased size of the liver.

hpo_phenotypes p=4.48e-09 (10 genes)

Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.

hpo_phenotypes p=4.48e-09 (8 genes)

Microcephaly

Head circumference below 2 standard deviations below the mean for age and gender.

hpo_phenotypes p=7.34e-09 (13 genes)

ORPHA:231160

hpo_diseases p=1.69e-06 (14 genes)

Feature 14526

1,055,040 activations

Top Activating Genes

CD164 act: 64.42 (99.0%ile) | freq: 247003/1055040 (23.41%)

TMEM30A act: 62.60 (98.0%ile) | freq: 128106/1055040 (12.14%)

SLC25A24 act: 58.76 (97.0%ile) | freq: 64828/1055040 (6.14%)

TMEM123 act: 58.62 (96.0%ile) | freq: 180306/1055040 (17.09%)

TMED7 act: 57.35 (95.0%ile) | freq: 88623/1055040 (8.40%)

DCK act: 54.48 (94.0%ile) | freq: 59182/1055040 (5.61%)

EIF4G2 act: 54.12 (93.0%ile) | freq: 283128/1055040 (26.84%)

CD46 act: 53.86 (92.0%ile) | freq: 169537/1055040 (16.07%)

PRKAR1A act: 53.60 (91.0%ile) | freq: 180877/1055040 (17.14%)

TWF1 act: 51.30 (90.0%ile) | freq: 50962/1055040 (4.83%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=7.21e-08 (18 genes)

OMIM:187900

hpo_diseases p=9.72e-07 (17 genes)

Congenital onset

A phenotypic abnormality that is present at birth.

hpo_phenotypes p=1.88e-04 (8 genes)

Delayed speech and language development

A degree of language development that is significantly below the norm for a child of a specified age.

hpo_phenotypes p=1.88e-04 (9 genes)

Hip dislocation

Displacement of the femur from its normal location in the hip joint.

hpo_phenotypes p=1.88e-04 (7 genes)

Feature 14773

1,055,040 activations

Top Activating Genes

RPL18A act: 92.64 (99.0%ile) | freq: 476684/1055040 (45.18%)

RPS3A act: 89.90 (98.0%ile) | freq: 473957/1055040 (44.92%)

RPSA act: 72.03 (97.0%ile) | freq: 403478/1055040 (38.24%)

RPS7 act: 70.32 (96.0%ile) | freq: 473235/1055040 (44.85%)

RPL21 act: 69.08 (95.0%ile) | freq: 483927/1055040 (45.87%)

RPL41 act: 61.93 (94.0%ile) | freq: 537386/1055040 (50.94%)

RPL22 act: 61.57 (93.0%ile) | freq: 419960/1055040 (39.81%)

RPL10 act: 59.70 (92.0%ile) | freq: 536356/1055040 (50.84%)

RPL6 act: 59.43 (91.0%ile) | freq: 467877/1055040 (44.35%)

RPL29 act: 58.27 (90.0%ile) | freq: 457427/1055040 (43.36%)

🔬 Biological Validation

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=1.78e-12 (5 genes)

Thrombocytosis

Increased numbers of platelets in the peripheral blood.

hpo_phenotypes p=1.39e-10 (6 genes)

Abnormality of the thenar eminence

An abnormality of the thenar eminence, i.e., of the muscle on the palm of the human hand just beneath the thumb.

hpo_phenotypes p=1.39e-10 (5 genes)

Radial artery aplasia

Congenital absence of the radial artery.

hpo_phenotypes p=1.39e-10 (5 genes)

Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

gencc p=1.27e-09 (4 genes)

Feature 14921

1,055,040 activations

Top Activating Genes

RND3 act: 67.91 (99.0%ile) | freq: 43855/1055040 (4.16%)

PLK2 act: 64.60 (98.0%ile) | freq: 39651/1055040 (3.76%)

KLF5 act: 57.53 (97.0%ile) | freq: 44389/1055040 (4.21%)

CITED2 act: 56.76 (96.0%ile) | freq: 137398/1055040 (13.02%)

PHLDA1 act: 56.73 (95.0%ile) | freq: 106125/1055040 (10.06%)

NR2F2 act: 56.71 (94.0%ile) | freq: 41296/1055040 (3.91%)

MYC act: 56.23 (93.0%ile) | freq: 60943/1055040 (5.78%)

SPRY2 act: 55.03 (92.0%ile) | freq: 35077/1055040 (3.32%)

IRX5 act: 55.00 (91.0%ile) | freq: 4670/1055040 (0.44%)

PTGER4 act: 54.29 (90.0%ile) | freq: 79062/1055040 (7.49%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=5.20e-09 (21 genes)

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=1.99e-06 (15 genes)

Proptosis

An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

hpo_phenotypes p=1.99e-06 (10 genes)

OMIM:187900

hpo_diseases p=3.11e-06 (18 genes)

Cleft palate

Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

hpo_phenotypes p=6.25e-06 (10 genes)

Feature 15521

1,055,040 activations

Top Activating Genes

MKI67 act: 88.37 (99.0%ile) | freq: 1737/1055040 (0.16%)

CFAP276 act: 86.25 (98.0%ile) | freq: 1929/1055040 (0.18%)

ANLN act: 85.82 (97.0%ile) | freq: 858/1055040 (0.08%)

C20orf85 act: 84.84 (96.0%ile) | freq: 1315/1055040 (0.12%)

MCM10 act: 84.16 (95.0%ile) | freq: 403/1055040 (0.04%)

DYNLRB2 act: 83.84 (94.0%ile) | freq: 1259/1055040 (0.12%)

CFAP210 act: 83.65 (93.0%ile) | freq: 506/1055040 (0.05%)

SRGAP3-AS2 act: 83.60 (92.0%ile) | freq: 6/1055040 (0.00%)

CCDC40 act: 83.00 (91.0%ile) | freq: 1929/1055040 (0.18%)

CFAP144 act: 82.50 (90.0%ile) | freq: 700/1055040 (0.07%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=5.37e-06 (17 genes)

autosomal recessive primary microcephaly

Autosomal recessive primary microcephaly (MCPH) is a rare genetically heterogeneous disorder of neurogenic brain development characterized by reduced head circumference at birth with no gross anomalies of brain architecture and variable degrees of intellectual impairment.

gencc p=7.37e-06 (3 genes)

Autosomal recessive primary microcephaly

Autosomal recessive primary microcephaly (MCPH) is a rare genetically heterogeneous disorder of neurogenic brain development characterized by reduced head circumference at birth with no gross anomalies of brain architecture and variable degrees of intellectual impairment.

orphanet p=8.64e-06 (3 genes)

ORPHA:231160

hpo_diseases p=1.00e-04 (14 genes)

Autosomal recessive primary microcephaly

clinvar p=4.52e-04 (2 genes)

Feature 15763

1,055,040 activations

Top Activating Genes

ZYX act: 72.14 (99.0%ile) | freq: 114661/1055040 (10.87%)

SYNGR2 act: 71.75 (98.0%ile) | freq: 125438/1055040 (11.89%)

PPP2R1A act: 63.65 (97.0%ile) | freq: 148923/1055040 (14.12%)

OTUB1 act: 63.56 (96.0%ile) | freq: 111757/1055040 (10.59%)

ERGIC3 act: 61.40 (95.0%ile) | freq: 142742/1055040 (13.53%)

DAZAP2 act: 60.61 (94.0%ile) | freq: 258918/1055040 (24.54%)

GRINA act: 57.11 (93.0%ile) | freq: 181159/1055040 (17.17%)

PNPLA2 act: 54.70 (92.0%ile) | freq: 90251/1055040 (8.55%)

GNB2 act: 54.07 (91.0%ile) | freq: 196854/1055040 (18.66%)

RPN1 act: 53.88 (90.0%ile) | freq: 157059/1055040 (14.89%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=1.69e-06 (18 genes)

OMIM:187900

hpo_diseases p=3.26e-06 (18 genes)

Intellectual disability

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

hpo_phenotypes p=2.46e-04 (12 genes)

Microcephaly

Head circumference below 2 standard deviations below the mean for age and gender.

hpo_phenotypes p=2.46e-04 (11 genes)

Global developmental delay

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

hpo_phenotypes p=2.75e-04 (12 genes)

Feature 16432

1,055,040 activations

Top Activating Genes

NRIP1 act: 71.05 (99.0%ile) | freq: 35456/1055040 (3.36%)

FOXP1 act: 70.80 (98.0%ile) | freq: 75419/1055040 (7.15%)

SRGAP2 act: 70.22 (97.0%ile) | freq: 12982/1055040 (1.23%)

SH3RF1 act: 69.88 (96.0%ile) | freq: 6553/1055040 (0.62%)

LINC02882 act: 69.69 (95.0%ile) | freq: 6336/1055040 (0.60%)

STXBP6 act: 69.61 (94.0%ile) | freq: 4400/1055040 (0.42%)

ARID5B act: 69.42 (93.0%ile) | freq: 59182/1055040 (5.61%)

ELOVL5 act: 69.20 (92.0%ile) | freq: 12302/1055040 (1.17%)

NECAB1 act: 69.20 (91.0%ile) | freq: 12886/1055040 (1.22%)

CFLAR act: 68.90 (90.0%ile) | freq: 78594/1055040 (7.45%)

🔬 Biological Validation

Lymphocyte count

A quantification of lymphocytes in blood.

gwas p=5.01e-05 (8 genes)

Chromatinopathy

clinvar p=1.86e-04 (2 genes)

Fever

Body temperature elevated above the normal range.

hpo_phenotypes p=7.65e-04 (6 genes)

Cardiometabolic and hematological traits

The number of PLATELETS per unit volume in a sample of venous BLOOD.

gwas p=8.68e-04 (8 genes)

Pulse pressure

quantification of the difference between systolic blood pressure and diastolic blood pressure. Higher PP is associated with left ventricle hypertrophy and the increased intimal thickness of the carotid artery, which represent early target organ damage in cardiovascular diseases

gwas p=8.68e-04 (7 genes)

Feature 16932

1,055,040 activations

Top Activating Genes

NIPBL act: 63.58 (99.0%ile) | freq: 172945/1055040 (16.39%)

KMT2C act: 60.75 (98.0%ile) | freq: 176513/1055040 (16.73%)

USP34 act: 59.22 (97.0%ile) | freq: 178046/1055040 (16.88%)

ASH1L act: 58.43 (96.0%ile) | freq: 182180/1055040 (17.27%)

BIRC6 act: 56.47 (95.0%ile) | freq: 163060/1055040 (15.46%)

NFAT5 act: 56.37 (94.0%ile) | freq: 149955/1055040 (14.21%)

AKAP13 act: 53.98 (93.0%ile) | freq: 201096/1055040 (19.06%)

NF1 act: 53.91 (92.0%ile) | freq: 124586/1055040 (11.81%)

KMT2E act: 53.78 (91.0%ile) | freq: 250148/1055040 (23.71%)

JMJD1C act: 53.77 (90.0%ile) | freq: 231281/1055040 (21.92%)

🔬 Biological Validation

Neurodevelopmental delay

clinvar p=7.95e-20 (12 genes)

Intellectual disability

clinvar p=6.85e-19 (18 genes)

Global developmental delay

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

hpo_phenotypes p=2.13e-15 (25 genes)

Global developmental delay

clinvar p=3.22e-15 (11 genes)

Autistic behavior

Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.

hpo_phenotypes p=4.36e-15 (15 genes)

Feature 17097

1,055,040 activations

Top Activating Genes

SERTAD1 act: 62.83 (99.0%ile) | freq: 77653/1055040 (7.36%)

BRD2 act: 61.85 (98.0%ile) | freq: 162721/1055040 (15.42%)

UBE2S act: 61.26 (97.0%ile) | freq: 70776/1055040 (6.71%)

TUBB4B act: 56.64 (96.0%ile) | freq: 184832/1055040 (17.52%)

POLR2A act: 55.20 (95.0%ile) | freq: 129205/1055040 (12.25%)

SNHG12 act: 54.81 (94.0%ile) | freq: 70104/1055040 (6.64%)

DNAJA1 act: 54.39 (93.0%ile) | freq: 224413/1055040 (21.27%)

INTS6 act: 50.67 (92.0%ile) | freq: 125782/1055040 (11.92%)

FAM53C act: 50.26 (91.0%ile) | freq: 53260/1055040 (5.05%)

H2AX act: 50.06 (90.0%ile) | freq: 43032/1055040 (4.08%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=1.30e-07 (18 genes)

Myxoid/round cell liposarcoma

Myxoid/round cell liposarcoma (MRCLS) is a type of liposarcoma (LS) mostly located in the limbs, with a variable behavior depending on the histological subtype. Both myxoid and round cell are distinct histological subtypes of LS.

orphanet p=2.05e-06 (2 genes)

Gliosis

Gliosis is the focal proliferation of glial cells in the central nervous system.

hpo_phenotypes p=3.92e-04 (4 genes)

Hereditary breast ovarian cancer syndrome

clinvar p=5.34e-04 (2 genes)

Amyotrophic lateral sclerosis

A neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord.

orphanet p=5.64e-04 (2 genes)

Feature 17175

1,055,040 activations

Top Activating Genes

RPL32 act: 79.65 (99.0%ile) | freq: 435105/1055040 (41.24%)

RPS23 act: 75.56 (98.0%ile) | freq: 397663/1055040 (37.69%)

RPL12 act: 74.00 (97.0%ile) | freq: 439244/1055040 (41.63%)

RPS14 act: 73.97 (96.0%ile) | freq: 459094/1055040 (43.51%)

RPS15A act: 72.36 (95.0%ile) | freq: 342432/1055040 (32.46%)

RPL11 act: 72.18 (94.0%ile) | freq: 379024/1055040 (35.93%)

RPS27A act: 71.64 (93.0%ile) | freq: 381903/1055040 (36.20%)

RPL19 act: 70.15 (92.0%ile) | freq: 381407/1055040 (36.15%)

RPS24 act: 69.21 (91.0%ile) | freq: 424934/1055040 (40.28%)

RPS8 act: 69.06 (90.0%ile) | freq: 406239/1055040 (38.50%)

🔬 Biological Validation

Erythroid hypoplasia

Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.

hpo_phenotypes p=4.81e-36 (14 genes)

Abnormality of the thenar eminence

An abnormality of the thenar eminence, i.e., of the muscle on the palm of the human hand just beneath the thumb.

hpo_phenotypes p=1.34e-34 (13 genes)

Radial artery aplasia

Congenital absence of the radial artery.

hpo_phenotypes p=1.34e-34 (13 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=1.38e-33 (12 genes)

Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

gencc p=8.77e-31 (11 genes)

Feature 17454

1,055,040 activations

Top Activating Genes

FKBP1C act: 96.97 (99.0%ile) | freq: 5811/1055040 (0.55%)

HNRNPA1L2 act: 91.37 (98.0%ile) | freq: 25470/1055040 (2.41%)

H3-5 act: 88.66 (97.0%ile) | freq: 23736/1055040 (2.25%)

ENSG00000279081.2 act: 88.01 (96.0%ile) | freq: 224/1055040 (0.02%)

NACA2 act: 87.21 (95.0%ile) | freq: 24617/1055040 (2.33%)

ZNF90 act: 84.53 (94.0%ile) | freq: 31012/1055040 (2.94%)

ENSG00000277654.6 act: 83.05 (93.0%ile) | freq: 2566/1055040 (0.24%)

H2BC12L act: 82.48 (92.0%ile) | freq: 361/1055040 (0.03%)

RPS15AP38 act: 82.23 (91.0%ile) | freq: 5221/1055040 (0.49%)

GNG5B act: 79.75 (90.0%ile) | freq: 1862/1055040 (0.18%)

🔬 Biological Validation

No significant enrichments found

Feature 17940

1,055,040 activations

Top Activating Genes

VAMP8 act: 55.93 (99.0%ile) | freq: 183984/1055040 (17.44%)

RPS4Y1 act: 54.32 (98.0%ile) | freq: 96076/1055040 (9.11%)

ATP6V1G1 act: 53.06 (97.0%ile) | freq: 304194/1055040 (28.83%)

ERO1A act: 46.90 (96.0%ile) | freq: 111934/1055040 (10.61%)

GSN act: 46.48 (95.0%ile) | freq: 148686/1055040 (14.09%)

MIR205HG act: 43.53 (94.0%ile) | freq: 5350/1055040 (0.51%)

RND3 act: 42.89 (93.0%ile) | freq: 43853/1055040 (4.16%)

PPA1 act: 38.89 (92.0%ile) | freq: 182053/1055040 (17.26%)

SRP14 act: 38.78 (91.0%ile) | freq: 407617/1055040 (38.64%)

SEC61G act: 38.38 (90.0%ile) | freq: 265959/1055040 (25.21%)

🔬 Biological Validation

Abnormality of the nervous system

An abnormality of the nervous system.

hpo_phenotypes p=6.50e-03 (3 genes)

Seborrheic dermatitis

Seborrheic dermatitis is a form of eczema which is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk.

hpo_phenotypes p=6.50e-03 (2 genes)

Small earlobe

Reduced volume of the earlobe.

hpo_phenotypes p=6.50e-03 (2 genes)

OMIM:187900

hpo_diseases p=1.14e-02 (11 genes)

ORPHA:231160

hpo_diseases p=2.88e-02 (9 genes)

Feature 18002

1,055,040 activations

Top Activating Genes

PRDX1 act: 62.83 (99.0%ile) | freq: 250121/1055040 (23.71%)

TUBB4B act: 41.89 (98.0%ile) | freq: 184827/1055040 (17.52%)

COX6A1 act: 40.92 (97.0%ile) | freq: 288264/1055040 (27.32%)

BSG act: 40.55 (96.0%ile) | freq: 232982/1055040 (22.08%)

OCIAD2 act: 38.77 (95.0%ile) | freq: 109614/1055040 (10.39%)

UQCRH act: 37.42 (94.0%ile) | freq: 283481/1055040 (26.87%)

CYBA act: 36.25 (93.0%ile) | freq: 322146/1055040 (30.53%)

SLC6A6 act: 35.12 (92.0%ile) | freq: 75875/1055040 (7.19%)

ALDH1A1 act: 34.57 (91.0%ile) | freq: 87839/1055040 (8.33%)

EYS act: 34.39 (90.0%ile) | freq: 17537/1055040 (1.66%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=2.64e-12 (26 genes)

Attenuation of retinal blood vessels

hpo_phenotypes p=2.42e-11 (11 genes)

Constriction of peripheral visual field

An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye.

hpo_phenotypes p=1.38e-10 (10 genes)

Undetectable light- and dark-adapted electroretinogram

Absence of the combined rod-and-cone response on electroretinogram.

hpo_phenotypes p=1.38e-10 (10 genes)

ORPHA:231160

hpo_diseases p=8.60e-09 (21 genes)

Feature 18116

1,055,040 activations

Top Activating Genes

RPL23AP37 act: 128.87 (99.0%ile) | freq: 1940/1055040 (0.18%)

RPS26P2 act: 125.90 (98.0%ile) | freq: 1790/1055040 (0.17%)

APOE act: 122.01 (97.0%ile) | freq: 5228/1055040 (0.50%)

RPS2P55 act: 121.43 (96.0%ile) | freq: 3690/1055040 (0.35%)

RPL17P16 act: 121.10 (95.0%ile) | freq: 3460/1055040 (0.33%)

RPS20P5 act: 120.35 (94.0%ile) | freq: 2620/1055040 (0.25%)

IGLL5 act: 120.31 (93.0%ile) | freq: 8921/1055040 (0.85%)

ENSG00000178715.8 act: 120.28 (92.0%ile) | freq: 8941/1055040 (0.85%)

ENSG00000213280.2 act: 120.07 (91.0%ile) | freq: 3510/1055040 (0.33%)

ATG4B act: 119.78 (90.0%ile) | freq: 5096/1055040 (0.48%)

🔬 Biological Validation

recurrent infections associated with rare immunoglobulin isotypes deficiency

Deficiencies in immunoglobulin (Ig) isotypes (including: isolated IgG subclass deficiency, IgG subclass deficiency with IgA deficiency and kappa chain deficiency) are primary immunodeficiencies that are often asymptomatic but can be characterized by recurrent, often pyogenic, sinopulmonary infections.

gencc p=6.21e-08 (2 genes)

Recurrent infections associated with rare immunoglobulin isotypes deficiency

Deficiencies in immunoglobulin (Ig) isotypes (including: isolated IgG subclass deficiency, IgG sublcass deficiency with IgA deficiency and kappa chain deficiency) are primary immunodeficiencies that are often asymptomatic but can be characterized by recurrent, often pyogenic, sinopulmonary infections.

orphanet p=6.21e-08 (2 genes)

Pulmonary tuberculosis

A lung infection by Mycobacterium tuberculosis a slightly curved non-motile, aerobic, non-capsulated and non-spore forming strains of mycobacteria.

hpo_phenotypes p=3.91e-06 (2 genes)

Cerebrospinal fluid rhinorrhoea

Drainage of cerebrospinal fluid through the nose. This can occur when there is a fistula between the dura and the skull base and discharge of cerebrospinal fluid (CSF) from the nose.

hpo_phenotypes p=3.91e-06 (2 genes)

Viral hepatitis

Inflammation of the liver due to infection with a virus.

hpo_phenotypes p=3.91e-06 (2 genes)

Feature 18454

1,055,040 activations

Top Activating Genes

RPS12 act: 75.47 (99.0%ile) | freq: 509336/1055040 (48.28%)

TPT1 act: 66.74 (98.0%ile) | freq: 557645/1055040 (52.86%)

UBA52 act: 59.74 (97.0%ile) | freq: 458217/1055040 (43.43%)

RPL30 act: 58.36 (96.0%ile) | freq: 341187/1055040 (32.34%)

RPL7A act: 58.20 (95.0%ile) | freq: 284970/1055040 (27.01%)

NSA2 act: 57.88 (94.0%ile) | freq: 171298/1055040 (16.24%)

RPL9 act: 57.69 (93.0%ile) | freq: 483356/1055040 (45.81%)

RPL28 act: 57.15 (92.0%ile) | freq: 534873/1055040 (50.70%)

RPS24 act: 55.94 (91.0%ile) | freq: 509981/1055040 (48.34%)

RPL37 act: 55.88 (90.0%ile) | freq: 409786/1055040 (38.84%)

🔬 Biological Validation

Thrombocytosis

Increased numbers of platelets in the peripheral blood.

hpo_phenotypes p=4.37e-07 (5 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=2.34e-06 (3 genes)

Lethargy

A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.

hpo_phenotypes p=4.55e-06 (6 genes)

Pallor

Abnormally pale skin.

hpo_phenotypes p=6.72e-06 (5 genes)

Mitochondrial DNA-associated Leigh syndrome

Maternally inherited Leigh syndrome is a rare subtype of Leigh syndrome characterized clinically by encephalopathy, lactic acidosis, seizures, cardiomyopathy, respiratory disorders and developmental delay, with onset in infancy or early childhood, and resulting from maternally-inherited mutations in mitochondrial DNA.

orphanet p=4.97e-05 (2 genes)

Feature 18642

1,055,040 activations

Top Activating Genes

GSN act: 57.96 (99.0%ile) | freq: 148686/1055040 (14.09%)

CXCL1 act: 56.44 (98.0%ile) | freq: 57722/1055040 (5.47%)

RPS27A act: 54.31 (97.0%ile) | freq: 516505/1055040 (48.96%)

RPL7 act: 53.60 (96.0%ile) | freq: 440357/1055040 (41.74%)

DYNLL1 act: 50.72 (95.0%ile) | freq: 284933/1055040 (27.01%)

RPS14 act: 48.04 (94.0%ile) | freq: 515308/1055040 (48.84%)

CXCL2 act: 46.36 (93.0%ile) | freq: 113482/1055040 (10.76%)

RPL21 act: 44.70 (92.0%ile) | freq: 483360/1055040 (45.81%)

PKM act: 44.10 (91.0%ile) | freq: 290267/1055040 (27.51%)

CXCL3 act: 43.13 (90.0%ile) | freq: 71598/1055040 (6.79%)

🔬 Biological Validation

Thrombocytosis

Increased numbers of platelets in the peripheral blood.

hpo_phenotypes p=4.55e-05 (4 genes)

ORPHA:231160

hpo_diseases p=1.35e-04 (12 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=1.52e-04 (2 genes)

Diamond-Blackfan anemia

clinvar p=1.59e-04 (2 genes)

OMIM:187900

hpo_diseases p=1.66e-04 (12 genes)

Feature 18681

1,055,040 activations

Top Activating Genes

MYL12A act: 122.21 (99.0%ile) | freq: 142268/1055040 (13.48%)

PFN1 act: 121.50 (98.0%ile) | freq: 281776/1055040 (26.71%)

CD44 act: 121.50 (97.0%ile) | freq: 148516/1055040 (14.08%)

PKM act: 121.18 (96.0%ile) | freq: 57980/1055040 (5.50%)

JUN act: 120.91 (95.0%ile) | freq: 185260/1055040 (17.56%)

ENSG00000227088.2 act: 120.49 (94.0%ile) | freq: 2493/1055040 (0.24%)

COX4I1 act: 120.04 (93.0%ile) | freq: 147720/1055040 (14.00%)

DLC1 act: 119.83 (92.0%ile) | freq: 3024/1055040 (0.29%)

CYBA act: 119.81 (91.0%ile) | freq: 131266/1055040 (12.44%)

ALDOA act: 119.57 (90.0%ile) | freq: 98372/1055040 (9.32%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=3.96e-12 (24 genes)

ORPHA:231160

hpo_diseases p=3.46e-10 (21 genes)

Autosomal dominant inheritance

A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.

hpo_phenotypes p=7.74e-07 (15 genes)

Generalized hypotonia

Generalized muscular hypotonia (abnormally low muscle tone).

hpo_phenotypes p=4.68e-06 (9 genes)

Ptosis

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

hpo_phenotypes p=5.67e-06 (9 genes)

Feature 19297

1,055,040 activations

Top Activating Genes

LINC01843 act: 100.78 (99.0%ile) | freq: 1072/1055040 (0.10%)

RPAP1 act: 99.47 (98.0%ile) | freq: 1168/1055040 (0.11%)

ZNF573 act: 99.01 (97.0%ile) | freq: 56/1055040 (0.01%)

FBXO36 act: 98.48 (96.0%ile) | freq: 93/1055040 (0.01%)

INTS14 act: 98.03 (95.0%ile) | freq: 841/1055040 (0.08%)

ZNF839 act: 97.52 (94.0%ile) | freq: 617/1055040 (0.06%)

NMNAT1 act: 97.50 (93.0%ile) | freq: 1014/1055040 (0.10%)

ACBD7 act: 96.98 (92.0%ile) | freq: 80/1055040 (0.01%)

ELMOD2 act: 96.65 (91.0%ile) | freq: 144/1055040 (0.01%)

COA7 act: 95.85 (90.0%ile) | freq: 4750/1055040 (0.45%)

🔬 Biological Validation

Seizure

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

hpo_phenotypes p=4.19e-03 (8 genes)

Leukoencephalopathy

This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.

hpo_phenotypes p=4.19e-03 (3 genes)

Visual impairment

Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

hpo_phenotypes p=4.19e-03 (5 genes)

Leigh syndrome

A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.

gencc p=4.90e-03 (2 genes)

mitochondrial disease

gencc p=4.90e-03 (2 genes)

Feature 19710

1,055,040 activations

Top Activating Genes

RPS23 act: 130.44 (99.0%ile) | freq: 471634/1055040 (44.70%)

RPL5 act: 129.98 (98.0%ile) | freq: 412375/1055040 (39.09%)

RPL30 act: 127.76 (97.0%ile) | freq: 470044/1055040 (44.55%)

RPS3A act: 126.76 (96.0%ile) | freq: 459931/1055040 (43.59%)

RPL12 act: 125.29 (95.0%ile) | freq: 354146/1055040 (33.57%)

RPL35A act: 125.22 (94.0%ile) | freq: 461535/1055040 (43.75%)

RPL32 act: 124.12 (93.0%ile) | freq: 426352/1055040 (40.41%)

RPS7 act: 122.96 (92.0%ile) | freq: 394207/1055040 (37.36%)

RPS27A act: 122.41 (91.0%ile) | freq: 425168/1055040 (40.30%)

RPL10 act: 120.53 (90.0%ile) | freq: 383526/1055040 (36.35%)

🔬 Biological Validation

Erythroid hypoplasia

Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.

hpo_phenotypes p=5.60e-32 (13 genes)

Abnormality of the thenar eminence

An abnormality of the thenar eminence, i.e., of the muscle on the palm of the human hand just beneath the thumb.

hpo_phenotypes p=1.40e-30 (12 genes)

Radial artery aplasia

Congenital absence of the radial artery.

hpo_phenotypes p=1.40e-30 (12 genes)

Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

gencc p=7.98e-27 (10 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=2.58e-26 (10 genes)

Feature 20003

1,055,040 activations

Top Activating Genes

RPS6 act: 61.14 (99.0%ile) | freq: 297684/1055040 (28.22%)

RPS23 act: 59.10 (98.0%ile) | freq: 312395/1055040 (29.61%)

RPL37A act: 58.30 (97.0%ile) | freq: 377107/1055040 (35.74%)

SERF2 act: 58.24 (96.0%ile) | freq: 395655/1055040 (37.50%)

RPL6 act: 58.11 (95.0%ile) | freq: 240663/1055040 (22.81%)

RPL35 act: 57.19 (94.0%ile) | freq: 233967/1055040 (22.18%)

COX7B act: 56.97 (93.0%ile) | freq: 145147/1055040 (13.76%)

MT-ND1 act: 56.50 (92.0%ile) | freq: 263963/1055040 (25.02%)

RPL9 act: 56.34 (91.0%ile) | freq: 255470/1055040 (24.21%)

SEPTIN7 act: 56.34 (90.0%ile) | freq: 67063/1055040 (6.36%)

🔬 Biological Validation

ORPHA:231160

hpo_diseases p=4.67e-09 (17 genes)

Diamond-Blackfan anemia

Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.

orphanet p=8.24e-09 (4 genes)

Ptosis

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

hpo_phenotypes p=4.31e-08 (10 genes)

Lethargy

A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.

hpo_phenotypes p=8.27e-08 (7 genes)

Webbed neck

Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline.

hpo_phenotypes p=8.27e-08 (6 genes)

Feature 20352

1,055,040 activations

Top Activating Genes

RHOC act: 58.24 (99.0%ile) | freq: 106722/1055040 (10.12%)

CSTA act: 55.56 (98.0%ile) | freq: 71655/1055040 (6.79%)

CCND1 act: 55.48 (97.0%ile) | freq: 42444/1055040 (4.02%)

TIMP1 act: 49.27 (96.0%ile) | freq: 247806/1055040 (23.49%)

TPM2 act: 46.52 (95.0%ile) | freq: 26587/1055040 (2.52%)

LCN2 act: 41.50 (94.0%ile) | freq: 62937/1055040 (5.97%)

ZFP36L1 act: 39.94 (93.0%ile) | freq: 259842/1055040 (24.63%)

CNN3 act: 39.64 (92.0%ile) | freq: 76098/1055040 (7.21%)

CARD16 act: 39.60 (91.0%ile) | freq: 97552/1055040 (9.25%)

HSPB1 act: 39.31 (90.0%ile) | freq: 220814/1055040 (20.93%)

🔬 Biological Validation

OMIM:187900

hpo_diseases p=4.06e-04 (15 genes)

Adult onset

Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later.

hpo_phenotypes p=2.13e-03 (5 genes)

ORPHA:231160

hpo_diseases p=3.92e-03 (12 genes)

Pleural effusion

The presence of an excessive amount of fluid in the pleural cavity.

hpo_phenotypes p=6.33e-03 (3 genes)

Increased serum testosterone level

An elevated circulating testosterone level in the blood.

hpo_phenotypes p=6.33e-03 (2 genes)

Features

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Cells Analyzed

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🔬 Biological Validation

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