Hearing loss, autosomal recessive
diseaseOn this page
Also known as autosomal recessive isolated neurosensory deafness type DFNBautosomal recessive isolated sensorineural deafness type DFNBautosomal recessive non-syndromic neurosensory deafness type DFNBautosomal recessive non-syndromic sensorineural deafness type DFNBautosomal recessive nonsyndromic deafnessautosomal recessive nonsyndromic genetic deafnessdeafness, autosomal recessivedeafness, neurosensory nonsyndromic recessive, DFNnonsyndromic deafness, autosomal recessivenonsyndromic genetic deafness, autosomal recessive
Summary
Hearing loss, autosomal recessive (MONDO:0019588) is a disease (an umbrella term covering 102 Mondo subtypes) caused by variants in PDZD7, PTPRQ, and TRIOBP, with 78 cohort genes. The dominant Reactome pathway is Sensory processing of sound by outer hair cells of the cochlea (28 cohort genes).
At a glance
- Prevalence: Unknown (Worldwide)
- Causal genes: PDZD7 (GenCC Definitive), PTPRQ (GenCC Definitive), TRIOBP (GenCC Definitive)
- Umbrella term: 102 Mondo subtypes
- Cohort genes: 78
- ClinVar variants: 222
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hearing loss, autosomal recessive |
| Mondo ID | MONDO:0019588 |
| MeSH | C564609 |
| OMIM | 220290, 607197 |
| Orphanet | 90636 |
| DOID | DOID:0050565 |
| UMLS | C1846647 |
| MedGen | 337623 |
| GARD | 0018117 |
| Is cancer (heuristic) | no |
Also known as: autosomal recessive isolated neurosensory deafness type DFNB · autosomal recessive isolated sensorineural deafness type DFNB · autosomal recessive non-syndromic neurosensory deafness type DFNB · autosomal recessive non-syndromic sensorineural deafness type DFNB · autosomal recessive nonsyndromic deafness · autosomal recessive nonsyndromic genetic deafness · deafness, autosomal recessive · deafness, neurosensory nonsyndromic recessive, DFN · hearing loss, autosomal recessive · nonsyndromic deafness, autosomal recessive · nonsyndromic genetic deafness, autosomal recessive
Data availability: 222 ClinVar variants · 81 GenCC gene-disease records · 31 cell lines.
Disease family
An umbrella term covering 102 Mondo subtypes.
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › hearing loss, autosomal recessive
Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy
Subtypes (102): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
222 retrieved; paginated sample, class counts are floors:
84 pathogenic/likely pathogenic, 68 pathogenic, 28 likely pathogenic, 24 conflicting classifications of pathogenicity, 14 uncertain significance, 3 benign/likely benign, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 3338645 | NM_004004.6(GJB2):c.[101T>C;550C>T] | Pathogenic | criteria provided, single submitter | |
| 544692 | Multiple alleles | Pathogenic | no assertion criteria provided | |
| 562081 | NM_032119.4(ADGRV1):c.1055C>T (p.Pro352Leu) | ADGRV1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4387 | NM_057176.3(BSND):c.139G>A (p.Gly47Arg) | BSND | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4388 | NM_057176.3(BSND):c.35T>C (p.Ile12Thr) | BSND | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 45920 | NM_022124.6(CDH23):c.3481C>T (p.Arg1161Ter) | C10orf105 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 4921 | NM_022124.6(CDH23):c.3880C>T (p.Gln1294Ter) | C10orf105 | Pathogenic | criteria provided, single submitter |
| 3340148 | NM_016366.3(CABP2):c.274C>T (p.Arg92Ter) | CABP2 | Pathogenic | criteria provided, single submitter |
| 597198 | NM_016366.3(CABP2):c.637+1G>T | CABP2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3381828 | NM_022124.6(CDH23):c.9585T>G (p.Tyr3195Ter) | CDH23 | Pathogenic | criteria provided, single submitter |
| 444219 | NM_022124.6(CDH23):c.2866G>A (p.Glu956Lys) | CDH23 | Pathogenic | reviewed by expert panel |
| 45999 | NM_022124.6(CDH23):c.6049+1G>A | CDH23 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 46001 | NM_022124.6(CDH23):c.6050-9G>A | CDH23 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 4919 | NM_022124.6(CDH23):c.6133G>A (p.Asp2045Asn) | CDH23 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4920 | NM_022124.6(CDH23):c.6604G>A (p.Asp2202Asn) | CDH23 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 560885 | NM_022124.6(CDH23):c.8351_8352insCGAT (p.Leu2785fs) | CDH23 | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 619171 | NM_022124.6(CDH23):c.6083A>C (p.Asp2028Ala) | CDH23 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 861900 | NM_022124.6(CDH23):c.2968G>A (p.Asp990Asn) | CDH23 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 862821 | NM_022124.6(CDH23):c.7814A>G (p.Asn2605Ser) | CDH23 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 996634 | NM_022124.6(CDH23):c.7987TTC[1] (p.Phe2664del) | CDH23 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3340146 | NM_001039213.4(CEACAM16):c.436C>T (p.Arg146Ter) | CEACAM16 | Pathogenic | criteria provided, single submitter |
| 39686 | NM_006383.4(CIB2):c.297C>G (p.Cys99Trp) | CIB2 | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 560887 | NM_004070.4(CLCNKA):c.1985G>T (p.Gly662Val) | CLCNKA | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 3338644 | NM_001146079.2(CLDN14):c.291C>A (p.Cys97Ter) | CLDN14 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4851 | NM_001146079.2(CLDN14):c.254T>A (p.Val85Asp) | CLDN14-AS1 | Pathogenic | criteria provided, single submitter |
| 562076 | NM_031475.3(ESPN):c.2496del (p.Gly831_Tyr832insTer) | ESPN | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 871900 | NM_133261.3(GIPC3):c.662C>T (p.Thr221Ile) | GIPC3 | Pathogenic | criteria provided, single submitter |
| 17001 | NM_004004.6(GJB2):c.231G>A (p.Trp77Ter) | GJB2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 17002 | NM_004004.6(GJB2):c.71G>A (p.Trp24Ter) | GJB2 | Pathogenic | reviewed by expert panel |
| 17004 | NM_004004.6(GJB2):c.35del (p.Gly12fs) | GJB2 | Pathogenic | reviewed by expert panel |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 585 · Orphanet: 136 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| CABP2 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 4 |
| CDC14A | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 4 |
| CDH23 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 8 |
| CIB2 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 7 |
| CLDN14 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 4 |
| COL11A2 | Definitive | Autosomal dominant | autosomal dominant nonsyndromic hearing loss 13 | 20 |
| ESPN | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 12 |
| ESRRB | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 6 |
| GIPC3 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 5 |
| GJB2 | Definitive | Autosomal dominant | hearing loss disorder | 26 |
| GRXCR1 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 6 |
| ILDR1 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 5 |
| LHFPL5 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 5 |
| LMX1A | Definitive | Autosomal dominant | autosomal dominant nonsyndromic hearing loss | 7 |
| LOXHD1 | Definitive | Autosomal recessive | autosomal recessive nonsyndromic hearing loss 77 | 7 |
| LRTOMT | Definitive | Unknown | autosomal recessive nonsyndromic hearing loss 63 | 5 |
| MARVELD2 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 6 |
| MPZL2 | Definitive | Autosomal recessive | hearing loss, autosomal recessive 111 | 5 |
| MSRB3 | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 6 |
| MYO15A | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 5 |
| MYO3A | Definitive | Autosomal recessive | autosomal recessive nonsyndromic hearing loss 30 | 7 |
| MYO6 | Definitive | Autosomal dominant | autosomal dominant nonsyndromic hearing loss 22 | 11 |
| MYO7A | Definitive | Autosomal dominant | nonsyndromic genetic hearing loss | 15 |
| OTOA | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 6 |
| OTOF | Definitive | Unknown | autosomal recessive nonsyndromic hearing loss 9 | 5 |
| OTOG | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 6 |
| OTOGL | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 6 |
| PCDH15 | Definitive | Autosomal recessive | autosomal recessive nonsyndromic hearing loss 23 | 9 |
| PDZD7 | Definitive | Unknown | hearing loss, autosomal recessive | 4 |
| PJVK | Definitive | Autosomal recessive | nonsyndromic genetic hearing loss | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TECTA | Orphanet:90635 | Rare autosomal dominant non-syndromic sensorineural deafness type DFNA |
| TECTA | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| TMPRSS3 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| USH1C | Orphanet:231169 | Usher syndrome type 1 |
| USH1C | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| ESPN | Orphanet:231169 | Usher syndrome type 1 |
| ESPN | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| CLIC5 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| CDH23 | Orphanet:231169 | Usher syndrome type 1 |
| CDH23 | Orphanet:2965 | Prolactinoma |
| CDH23 | Orphanet:314777 | Familial isolated pituitary adenoma |
| CDH23 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| CDH23 | Orphanet:91347 | TSH-secreting pituitary adenoma |
| CDH23 | Orphanet:96253 | Cushing disease |
| CABP2 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| PCDH15 | Orphanet:231169 | Usher syndrome type 1 |
| PCDH15 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| WHRN | Orphanet:231178 | Usher syndrome type 2 |
| WHRN | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| OTOA | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| BSND | Orphanet:89938 | Bartter syndrome type 4 |
| BSND | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| TMC1 | Orphanet:90635 | Rare autosomal dominant non-syndromic sensorineural deafness type DFNA |
| TMC1 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| TRIOBP | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| GIPC3 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| CLDN14 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| LHFPL5 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| CIB2 | Orphanet:231169 | Usher syndrome type 1 |
| CIB2 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| PDZD7 | Orphanet:231178 | Usher syndrome type 2 |
| MARVELD2 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| LOXHD1 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| TPRN | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| OTOGL | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| MSRB3 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| ILDR1 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| GPSM2 | Orphanet:314597 | Chudley-McCullough syndrome |
| GPSM2 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| PJVK | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| TMIE | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| GRXCR1 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| CEACAM16 | Orphanet:90635 | Rare autosomal dominant non-syndromic sensorineural deafness type DFNA |
| CEACAM16 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| GRXCR2 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| EPS8 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| ESRRB | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| MPZL2 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| GJB2 | Orphanet:166286 | Porokeratotic eccrine ostial and dermal duct nevus |
| GJB2 | Orphanet:2202 | Palmoplantar keratoderma-deafness syndrome |
Cohort genes → proteins
78 cohort genes, 77 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 78 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TECTA | HGNC:11720 | ENSG00000109927 | O75443 | Alpha-tectorin | gencc,clinvar |
| TMPRSS3 | HGNC:11877 | ENSG00000160183 | P57727 | Transmembrane protease serine 3 | gencc,clinvar |
| USH1C | HGNC:12597 | ENSG00000006611 | Q9Y6N9 | Harmonin | gencc,clinvar |
| ESPN | HGNC:13281 | ENSG00000187017 | B1AK53 | Espin | gencc,clinvar |
| CLIC5 | HGNC:13517 | ENSG00000112782 | Q9NZA1 | Chloride intracellular channel protein 5 | gencc,clinvar |
| CDH23 | HGNC:13733 | ENSG00000107736 | Q9H251 | Cadherin-23 | gencc,clinvar |
| CABP2 | HGNC:1385 | ENSG00000167791 | Q9NPB3 | Calcium-binding protein 2 | gencc,clinvar |
| PCDH15 | HGNC:14674 | ENSG00000150275 | Q96QU1 | Protocadherin-15 | gencc,clinvar |
| WHRN | HGNC:16361 | ENSG00000095397 | Q9P202 | Whirlin | gencc,clinvar |
| OTOA | HGNC:16378 | ENSG00000155719 | Q7RTW8 | Otoancorin | gencc,clinvar |
| BSND | HGNC:16512 | ENSG00000162399 | Q8WZ55 | Barttin | gencc,clinvar |
| TMC1 | HGNC:16513 | ENSG00000165091 | Q8TDI8 | Transmembrane channel-like protein 1 | gencc,clinvar |
| TRIOBP | HGNC:17009 | ENSG00000100106 | Q9H2D6 | TRIO and F-actin-binding protein | gencc,clinvar |
| GIPC3 | HGNC:18183 | ENSG00000179855 | Q8TF64 | PDZ domain-containing protein GIPC3 | gencc,clinvar |
| CLDN14 | HGNC:2035 | ENSG00000159261 | O95500 | Claudin-14 | gencc,clinvar |
| CLIC6 | HGNC:2065 | ENSG00000159212 | Q96NY7 | Chloride intracellular channel protein 6 | gencc,clinvar |
| LHFPL5 | HGNC:21253 | ENSG00000197753 | Q8TAF8 | LHFPL tetraspan subfamily member 5 protein | gencc,clinvar |
| CIB2 | HGNC:24579 | ENSG00000136425 | O75838 | Calcium and integrin-binding family member 2 | gencc,clinvar |
| PDZD7 | HGNC:26257 | ENSG00000186862 | Q9H5P4 | PDZ domain-containing protein 7 | gencc,clinvar |
| MARVELD2 | HGNC:26401 | ENSG00000152939 | Q8N4S9 | MARVEL domain-containing protein 2 | gencc,clinvar |
| LOXHD1 | HGNC:26521 | ENSG00000167210 | Q8IVV2 | Lipoxygenase homology domain-containing protein 1 | gencc,clinvar |
| TPRN | HGNC:26894 | ENSG00000176058 | Q4KMQ1 | Taperin | gencc,clinvar |
| OTOGL | HGNC:26901 | ENSG00000165899 | Q3ZCN5 | Otogelin-like protein | gencc,clinvar |
| MSRB3 | HGNC:27375 | ENSG00000174099 | Q8IXL7 | Methionine-R-sulfoxide reductase B3 | gencc,clinvar |
| ILDR1 | HGNC:28741 | ENSG00000145103 | Q86SU0 | Immunoglobulin-like domain-containing receptor 1 | gencc,clinvar |
| GPSM2 | HGNC:29501 | ENSG00000121957 | P81274 | G-protein-signaling modulator 2 | gencc,clinvar |
| PJVK | HGNC:29502 | ENSG00000204311 | Q0ZLH3 | Pejvakin | gencc,clinvar |
| TMIE | HGNC:30800 | ENSG00000181585 | Q8NEW7 | Transmembrane inner ear expressed protein | gencc,clinvar |
| GRXCR1 | HGNC:31673 | ENSG00000215203 | A8MXD5 | Glutaredoxin domain-containing cysteine-rich protein 1 | gencc,clinvar |
| CEACAM16 | HGNC:31948 | ENSG00000213892 | Q2WEN9 | Cell adhesion molecule CEACAM16 | gencc,clinvar |
| GRXCR2 | HGNC:33862 | ENSG00000204928 | A6NFK2 | Glutaredoxin domain-containing cysteine-rich protein 2 | gencc,clinvar |
| EPS8 | HGNC:3420 | ENSG00000151491 | Q12929 | Epidermal growth factor receptor kinase substrate 8 | gencc,clinvar |
| ESRRB | HGNC:3473 | ENSG00000119715 | O95718 | Steroid hormone receptor ERR2 | gencc,clinvar |
| MPZL2 | HGNC:3496 | ENSG00000149573 | O60487 | Myelin protein zero-like protein 2 | gencc,clinvar |
| GJB2 | HGNC:4284 | ENSG00000165474 | P29033 | Gap junction beta-2 protein | gencc,clinvar |
| GJB3 | HGNC:4285 | ENSG00000188910 | O75712 | Gap junction beta-3 protein | gencc,clinvar |
| GJB6 | HGNC:4288 | ENSG00000121742 | O95452 | Gap junction beta-6 protein | gencc,clinvar |
| KARS1 | HGNC:6215 | ENSG00000065427 | Q15046 | Lysine–tRNA ligase | gencc,clinvar |
| MYO15A | HGNC:7594 | ENSG00000091536 | Q9UKN7 | Unconventional myosin-XV | gencc,clinvar |
| MYO7A | HGNC:7606 | ENSG00000137474 | Q13402 | Unconventional myosin-VIIa | gencc,clinvar |
| OTOF | HGNC:8515 | ENSG00000115155 | Q9HC10 | Otoferlin | gencc,clinvar |
| OTOG | HGNC:8516 | ENSG00000188162 | Q6ZRI0 | Otogelin | gencc,clinvar |
| SLC26A4 | HGNC:8818 | ENSG00000091137 | O43511 | Pendrin | gencc,clinvar |
| PTPRQ | HGNC:9679 | ENSG00000139304 | Q9UMZ3 | Phosphatidylinositol phosphatase PTPRQ | gencc,clinvar |
| PTPRR | HGNC:9680 | ENSG00000153233 | Q15256 | Receptor-type tyrosine-protein phosphatase R | gencc,clinvar |
| ROR1 | HGNC:10256 | ENSG00000185483 | Q01973 | Inactive tyrosine-protein kinase transmembrane receptor ROR1 | gencc |
| RORA | HGNC:10258 | ENSG00000069667 | P35398 | Nuclear receptor ROR-alpha | gencc |
| SLC22A4 | HGNC:10968 | ENSG00000197208 | Q9H015 | Solute carrier family 22 member 4 | gencc |
| TSPEAR | HGNC:1268 | ENSG00000175894 | Q8WU66 | Thrombospondin-type laminin G domain and EAR repeat-containing protein | gencc |
| WBP2 | HGNC:12738 | ENSG00000132471 | Q969T9 | WW domain-binding protein 2 | gencc |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TECTA | Alpha-tectorin | One of the major non-collagenous components of the tectorial membrane. |
| TMPRSS3 | Transmembrane protease serine 3 | Probable serine protease that plays a role in hearing. |
| USH1C | Harmonin | Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. |
| ESPN | Espin | Multifunctional actin-bundling protein. |
| CLIC5 | Chloride intracellular channel protein 5 | In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor. |
| CDH23 | Cadherin-23 | Cadherins are calcium-dependent cell adhesion proteins. |
| CABP2 | Calcium-binding protein 2 | Required for sound encoding at inner hair cells (IHCs) synapses, likely via inhibition of the inactivation of voltage-gated calcium channel of type 1.3 (Cav1.3) in the IHCs. |
| PCDH15 | Protocadherin-15 | Calcium-dependent cell-adhesion protein. |
| WHRN | Whirlin | Involved in hearing and vision as member of the USH2 complex. |
| OTOA | Otoancorin | May act as an adhesion molecule. |
| BSND | Barttin | Regulatory subunit of anion-selective CLCNKA:BSND and CLCNKB:BSND heteromeric channels involved in basolateral chloride conductance along the nephron to achieve urine concentration and maintain systemic acid-base homeostasis, and in the st… |
| TMC1 | Transmembrane channel-like protein 1 | Pore-forming subunit of the mechanotransducer (MET) non-selective cation channel complex located at the tips of stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system. |
| TRIOBP | TRIO and F-actin-binding protein | Regulates actin cytoskeletal organization, cell spreading and cell contraction by directly binding and stabilizing filamentous F-actin and prevents its depolymerization. |
| GIPC3 | PDZ domain-containing protein GIPC3 | Required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion. |
| CLDN14 | Claudin-14 | Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. |
| CLIC6 | Chloride intracellular channel protein 6 | In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor. |
| LHFPL5 | LHFPL tetraspan subfamily member 5 protein | Auxiliary subunit of the mechanotransducer (MET) non-specific cation channel complex located at the tips of the shorter stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system. |
| CIB2 | Calcium and integrin-binding family member 2 | Calcium- and integrin-binding protein that plays a role in intracellular calcium homeostasis. |
| PDZD7 | PDZ domain-containing protein 7 | In cochlear developing hair cells, essential in organizing the USH2 complex at stereocilia ankle links. |
| MARVELD2 | MARVEL domain-containing protein 2 | Plays a role in the formation of tricellular tight junctions and of epithelial barriers. |
| LOXHD1 | Lipoxygenase homology domain-containing protein 1 | Involved in hearing. |
| TPRN | Taperin | Essential for hearing. |
| MSRB3 | Methionine-R-sulfoxide reductase B3 | Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine. |
| ILDR1 | Immunoglobulin-like domain-containing receptor 1 | Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (tTJs). |
| GPSM2 | G-protein-signaling modulator 2 | Plays an important role in mitotic spindle pole organization via its interaction with NUMA1. |
| PJVK | Pejvakin | Peroxisome-associated protein required to protect auditory hair cells against noise-induced damage. |
| TMIE | Transmembrane inner ear expressed protein | Auxiliary subunit of the mechanotransducer (MET) non-specific cation channel complex located at the tips of stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system. |
| GRXCR1 | Glutaredoxin domain-containing cysteine-rich protein 1 | May play a role in actin filament architecture in developing stereocilia of sensory cells. |
| CEACAM16 | Cell adhesion molecule CEACAM16 | Required for proper hearing, plays a role in maintaining the integrity of the tectorial membrane. |
| GRXCR2 | Glutaredoxin domain-containing cysteine-rich protein 2 | Required for hearing. |
| EPS8 | Epidermal growth factor receptor kinase substrate 8 | Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. |
| ESRRB | Steroid hormone receptor ERR2 | Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5’TCAAGGTCA-3’ localized on promoter and enhancer of targets genes regulating their expression or their transcription activity. |
| MPZL2 | Myelin protein zero-like protein 2 | Mediates homophilic cell-cell adhesion. |
| GJB2 | Gap junction beta-2 protein | Structural component of gap junctions. |
| GJB3 | Gap junction beta-3 protein | One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. |
| GJB6 | Gap junction beta-6 protein | One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. |
| KARS1 | Lysine–tRNA ligase | Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. |
| MYO15A | Unconventional myosin-XV | Myosins are actin-based motor molecules with ATPase activity. |
| MYO7A | Unconventional myosin-VIIa | Myosins are actin-based motor molecules with ATPase activity. |
| OTOF | Otoferlin | Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses. |
| OTOG | Otogelin | Glycoprotein specific to acellular membranes of the inner ear. |
| SLC26A4 | Pendrin | Sodium-independent transporter of chloride and iodide. |
| PTPRQ | Phosphatidylinositol phosphatase PTPRQ | Dephosphorylates phosphatidylinositol phosphates, such as phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 3,5-diphosphates, with preference for PIP3. |
| PTPRR | Receptor-type tyrosine-protein phosphatase R | Sequesters mitogen-activated protein kinases (MAPKs) such as MAPK1, MAPK3 and MAPK14 in the cytoplasm in an inactive form. |
| ROR1 | Inactive tyrosine-protein kinase transmembrane receptor ROR1 | Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo. |
| RORA | Nuclear receptor ROR-alpha | Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence. |
| SLC22A4 | Solute carrier family 22 member 4 | Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations. |
| TSPEAR | Thrombospondin-type laminin G domain and EAR repeat-containing protein | Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway. |
| WBP2 | WW domain-binding protein 2 | Acts as a transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation. |
| BDP1 | Transcription factor TFIIIB component B’’ homolog | General activator of RNA polymerase III transcription. |
Protein-family classification
Druggable: 22 · Difficult: 15 · Unknown: 41 · Druggable fraction: 0.28
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Scaffold/PPI | 13 | 2.9× | 0.005 |
| Nuclear receptor | 2 | 9.9× | 0.096 |
| Phosphatase | 3 | 3.2× | 0.218 |
| Transporter | 3 | 3.0× | 0.218 |
| Antibody/Immunoglobulin | 3 | 1.1× | 0.965 |
| Kinase | 3 | 1.1× | 0.965 |
| Other/Unknown | 41 | 0.9× | 0.965 |
| Protease | 2 | 0.9× | 0.965 |
| Enzyme (other) | 5 | 0.8× | 0.965 |
| GPCR | 1 | 0.3× | 1.000 |
| Transcription factor | 2 | 0.2× | 1.000 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TECTA | Other/Unknown | no | EGF, VWF_dom, ZP_dom | |
| TMPRSS3 | Protease | yes | SRCR, Trypsin_dom, Peptidase_S1A | |
| USH1C | Scaffold/PPI | no | PDZ, Harmonin_N, PDZ_sf | |
| ESPN | Scaffold/PPI | no | Ankyrin_rpt, WH2_dom, Ankyrin_rpt-contain_sf | |
| CLIC5 | Other/Unknown | no | CLIC, Glutathione-S-Trfase_C-like, Thioredoxin-like_sf | |
| CDH23 | Other/Unknown | no | Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS | |
| CABP2 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS | |
| PCDH15 | Other/Unknown | no | Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS | |
| WHRN | Scaffold/PPI | no | PDZ, Whirlin_HN-like_dom2, PDZ_sf | |
| OTOA | Other/Unknown | no | Stereocilin-rel | |
| BSND | Other/Unknown | no | Barttin | |
| TMC1 | Other/Unknown | no | TMC_dom, TMC | |
| TRIOBP | Scaffold/PPI | no | PH_domain, PH-like_dom_sf, M-RIP_PH | |
| GIPC3 | Scaffold/PPI | no | PDZ, GIPC1/2/3, PDZ_sf | |
| CLDN14 | Other/Unknown | no | PMP22/EMP/MP20/Claudin, Claudin, Claudin_CS | |
| CLIC6 | Other/Unknown | no | CLIC, Glutathione-S-Trfase_C-like, Thioredoxin-like_sf | |
| LHFPL5 | Other/Unknown | no | LHFPL | |
| CIB2 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS | |
| PDZD7 | Scaffold/PPI | no | PDZ, PDZ_sf, PDZD7_HN-like | |
| MARVELD2 | Other/Unknown | no | Marvel, Occludin_ELL, ELL/occludin | |
| LOXHD1 | Other/Unknown | no | PLAT/LH2_dom, PLAT/LH2_dom_sf, Inner_ear_hair_cell_LOXHD | |
| TPRN | Other/Unknown | no | Phostensin/Taperin_N_dom, Phostensin/Taperin_PP1-bd_dom, PPP1R18/Tprn | |
| OTOGL | Other/Unknown | no | VWF_dom, VWF_type-D, TIL_dom | |
| MSRB3 | Enzyme (other) | yes | 1.8.4.12 | Met_Sox_Rdtase_MsrB_dom, Mss4-like_sf, Met_Sox_Rdtase_MsrB |
| ILDR1 | Antibody/Immunoglobulin | yes | Ig_sub, LISCH7, Ig-like_fold | |
| GPSM2 | Other/Unknown | no | GoLoco_motif, TPR-like_helical_dom_sf, TPR_rpt | |
| PJVK | Other/Unknown | no | Gasdermin_pore, GSDME | |
| TMIE | Other/Unknown | no | TMIE | |
| GRXCR1 | Other/Unknown | no | Glutaredoxin, Thioredoxin-like_sf, GRXCR1 | |
| CEACAM16 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, Ig-like_dom | |
| GRXCR2 | Other/Unknown | no | GRXCR2, HSP_DnaJ_Cys-rich_dom_sf | |
| EPS8 | Scaffold/PPI | no | SH3_domain, PTB/PI_dom, PH-like_dom_sf | |
| ESRRB | Nuclear receptor | yes | Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt | |
| MPZL2 | Antibody/Immunoglobulin | yes | Myelin_P0-rel, Ig_sub, Ig-like_dom | |
| GJB2 | Other/Unknown | no | Connexin, Connexin26, Connexin_N | |
| GJB3 | Other/Unknown | no | Connexin, Connexin31, Connexin_N | |
| GJB6 | Other/Unknown | no | Connexin, Connexin_N, Connexin_CS | |
| KARS1 | Enzyme (other) | yes | 6.1.1.6 | Lys-tRNA-ligase_II, Aa-tRNA-synt_II, NA-bd_OB_tRNA |
| MYO15A | Scaffold/PPI | no | IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom | |
| MYO7A | Scaffold/PPI | no | IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom | |
| OTOF | Other/Unknown | no | C2_dom, Ferlin_B-domain, FerIin_dom | |
| OTOG | Other/Unknown | no | EGF, VWF_dom, VWF_type-D | |
| SLC26A4 | Transporter | yes | SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom | |
| PTPRQ | Phosphatase | yes | 3.1.3.48 | PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat |
| PTPRR | Phosphatase | yes | 3.1.3.48 | PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat |
| ROR1 | Kinase | yes | 2.7.10.1 | Kringle, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom |
| RORA | Nuclear receptor | yes | Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt | |
| SLC22A4 | Transporter | yes | Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS | |
| TSPEAR | Other/Unknown | no | EPTP, EAR, ConA-like_dom_sf | |
| WBP2 | Other/Unknown | no | GRAM, WBP2-like |
Expression context
Cohort genes with no expression data: 0.
67 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 2 |
| broad (>20) | 76 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 13 |
| primordial germ cell in gonad | 8 |
| left testis | 6 |
| right hemisphere of cerebellum | 6 |
| right testis | 5 |
| apex of heart | 5 |
| cerebellar cortex | 5 |
| cerebellar hemisphere | 5 |
| secondary oocyte | 4 |
| bronchial epithelial cell | 4 |
| gingival epithelium | 4 |
| oocyte | 3 |
| parotid gland | 3 |
| right uterine tube | 3 |
| mucosa of transverse colon | 3 |
| adrenal tissue | 3 |
| right adrenal gland cortex | 3 |
| testis | 3 |
| kidney epithelium | 3 |
| metanephros cortex | 3 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TECTA | 166 | marker | oocyte, secondary oocyte, parotid gland | |
| TMPRSS3 | 177 | tissue_specific | marker | pancreatic ductal cell, right uterine tube, bronchial epithelial cell |
| USH1C | 203 | broad | marker | mucosa of transverse colon, C1 segment of cervical spinal cord, rectum |
| ESPN | 184 | broad | marker | right testis, left testis, right uterine tube |
| CLIC5 | 260 | broad | marker | renal glomerulus, metanephric glomerulus, synovial joint |
| CDH23 | 161 | broad | marker | ventricular zone, left ovary, right ovary |
| CABP2 | 13 | tissue_specific | marker | parotid gland, myocardium, skeletal muscle tissue of biceps brachii |
| PCDH15 | 130 | tissue_specific | marker | left adrenal gland cortex, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue |
| WHRN | 226 | ubiquitous | marker | right adrenal gland cortex, left adrenal gland, right adrenal gland |
| OTOA | 86 | yes | primordial germ cell in gonad, left testis, testis | |
| BSND | 22 | tissue_specific | marker | kidney epithelium, adult mammalian kidney, metanephros cortex |
| TMC1 | 150 | marker | male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, primordial germ cell in gonad | |
| TRIOBP | 289 | ubiquitous | marker | lower lobe of lung, cervix squamous epithelium, apex of heart |
| GIPC3 | 157 | tissue_specific | yes | apex of heart, stromal cell of endometrium, lower esophagus muscularis layer |
| CLDN14 | 84 | tissue_specific | marker | right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis |
| CLIC6 | 189 | broad | marker | pigmented layer of retina, bronchial epithelial cell, bronchus |
| LHFPL5 | 161 | tissue_specific | marker | body of pancreas, male germ line stem cell (sensu Vertebrata) in testis, pancreas |
| CIB2 | 272 | ubiquitous | marker | right atrium auricular region, cardiac atrium, apex of heart |
| PDZD7 | 178 | broad | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| MARVELD2 | 129 | broad | marker | islet of Langerhans, primordial germ cell in gonad, duodenum |
| LOXHD1 | 135 | tissue_specific | marker | left testis, right testis, testis |
| TPRN | 197 | ubiquitous | marker | mucosa of transverse colon, body of pancreas, right hemisphere of cerebellum |
| OTOGL | 152 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, right atrium auricular region, cardiac atrium |
| MSRB3 | 252 | ubiquitous | marker | saphenous vein, cardiac muscle of right atrium, urethra |
| ILDR1 | 140 | broad | marker | corpus epididymis, kidney epithelium, nasal cavity epithelium |
| GPSM2 | 287 | ubiquitous | marker | tibia, buccal mucosa cell, amniotic fluid |
| PJVK | 188 | tissue_specific | yes | sperm, right testis, left testis |
| TMIE | 167 | broad | yes | primordial germ cell in gonad, hypothalamus, anterior cingulate cortex |
| GRXCR1 | 7 | marker | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, colonic epithelium | |
| CEACAM16 | 26 | yes | colonic epithelium, body of pancreas, mucosa of transverse colon |
Protein interactions among cohort
Intra-cohort edges: 298.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| IL6 | 9,239 |
| MET | 5,823 |
| KARS1 | 4,681 |
| HGF | 3,844 |
| PNPT1 | 3,741 |
| RDX | 3,167 |
| MYO6 | 2,972 |
| WHRN | 2,499 |
| CIB2 | 2,249 |
| NARS2 | 2,248 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| BSND | SLC26A4 | string_interaction |
| CABP2 | GRXCR1 | string_interaction |
| CABP2 | GRXCR2 | string_interaction |
| CABP2 | ILDR1 | string_interaction |
| CABP2 | OTOF | string_interaction |
| CABP2 | OTOG | string_interaction |
| CABP2 | PJVK | string_interaction |
| CABP2 | STRC | string_interaction |
| CABP2 | TMIE | string_interaction |
| CDH23 | CEACAM16 | string_interaction |
| CDH23 | CIB2 | string_interaction |
| CDH23 | CLIC5 | string_interaction |
| CDH23 | CLIC6 | string_interaction |
| CDH23 | ESPN | string_interaction |
| CDH23 | GJB2 | string_interaction |
| CDH23 | GJB3 | string_interaction |
| CDH23 | GJB6 | string_interaction |
| CDH23 | GRXCR1 | string_interaction |
| CDH23 | LHFPL5 | string_interaction |
| CDH23 | LOXHD1 | string_interaction |
| CDH23 | MYO15A | string_interaction |
| CDH23 | MYO3A | string_interaction |
| CDH23 | MYO6 | string_interaction |
| CDH23 | OTOA | string_interaction |
| CDH23 | OTOF | string_interaction |
| CDH23 | OTOG | string_interaction |
| CDH23 | OTOGL | string_interaction |
| CDH23 | PCDH15 | string_interaction |
| CDH23 | PDZD7 | string_interaction |
| CDH23 | PJVK | string_interaction |
| CDH23 | SLC26A5 | string_interaction |
| CDH23 | STRC | string_interaction |
| CDH23 | TMC1 | string_interaction |
| CDH23 | TMIE | string_interaction |
| CDH23 | TMPRSS3 | string_interaction |
| CDH23 | TRIOBP | string_interaction |
| CDH23 | USH1C | biogrid_interaction, intact |
| CDH23 | WHRN | string_interaction |
| CEACAM16 | GPSM2 | string_interaction |
| CEACAM16 | GRXCR1 | string_interaction |
| CEACAM16 | LOXHD1 | string_interaction |
| CEACAM16 | OTOA | string_interaction |
| CEACAM16 | OTOG | string_interaction |
| CEACAM16 | OTOGL | string_interaction |
| CEACAM16 | SLC26A5 | string_interaction |
| CEACAM16 | STRC | string_interaction |
| CEACAM16 | TECTA | string_interaction |
| CEACAM16 | TPRN | string_interaction |
| CEACAM16 | TSPEAR | string_interaction |
| CIB2 | LHFPL5 | string_interaction |
Structural data
PDB: 37 · AlphaFold-only: 40 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| MET | P08581 | 130 |
| HGF | P14210 | 36 |
| GJB2 | P29033 | 24 |
| PPIP5K2 | O43314 | 21 |
| IL6 | P05231 | 17 |
| KARS1 | Q15046 | 14 |
| BDP1 | A6H8Y1 | 13 |
| USH1C | Q9Y6N9 | 11 |
| PNPT1 | Q8TCS8 | 11 |
| PCDH15 | Q96QU1 | 8 |
| MYO6 | Q9UM54 | 8 |
| GPSM2 | P81274 | 7 |
| CDH23 | Q9H251 | 6 |
| WHRN | Q9P202 | 5 |
| ROR1 | Q01973 | 5 |
| SLC26A5 | P58743 | 4 |
| CLIC5 | Q9NZA1 | 3 |
| MARVELD2 | Q8N4S9 | 3 |
| ESRRB | O95718 | 3 |
| RORA | P35398 | 3 |
| LMX1A | Q8TE12 | 3 |
| PDZD7 | Q9H5P4 | 2 |
| MSRB3 | Q8IXL7 | 2 |
| EPS8 | Q12929 | 2 |
| EPS8L2 | Q9H6S3 | 2 |
| SYNE4 | Q8N205 | 2 |
| S1PR2 | O95136 | 2 |
| RDX | P35241 | 2 |
| TMC1 | Q8TDI8 | 1 |
| CIB2 | O75838 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| NARS2 | Q96I59 | 91.59 |
| SERPINB6 | P35237 | 91.25 |
| CEACAM16 | Q2WEN9 | 90.50 |
| MPZL2 | O60487 | 89.54 |
| LHFPL5 | Q8TAF8 | 89.11 |
| TSPEAR | Q8WU66 | 87.47 |
| TMPRSS3 | P57727 | 87.09 |
| GRAP | Q13588 | 86.28 |
| GIPC3 | Q8TF64 | 85.45 |
| SLC22A4 | Q9H015 | 85.07 |
| TBC1D24 | Q9ULP9 | 84.46 |
| OTOA | Q7RTW8 | 84.12 |
| LOXHD1 | Q8IVV2 | 84.00 |
| SLC26A4 | O43511 | 82.72 |
| GJB6 | O95452 | 82.33 |
| CLDN14 | O95500 | 80.00 |
| GJB3 | O75712 | 79.29 |
| ADCY1 | Q08828 | 78.34 |
| TECTA | O75443 | 77.64 |
| OTOF | Q9HC10 | 76.98 |
| ELMOD3 | Q96FG2 | 76.18 |
| GRXCR1 | A8MXD5 | 75.36 |
| CDC14A | Q9UNH5 | 73.77 |
| WBP2 | Q969T9 | 72.55 |
| TMEM132E | Q6IEE7 | 72.44 |
| OTOGL | Q3ZCN5 | 72.19 |
| STRC | Q7RTU9 | 69.21 |
| CABP2 | Q9NPB3 | 68.93 |
| ESPN | B1AK53 | 68.76 |
| PJVK | Q0ZLH3 | 68.16 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 239. Enrichment computed across 92 evidence-associated genes (67 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 67 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Sensory processing of sound by outer hair cells of the cochlea | 28 | 85.2× | 7e-48 | USH1C, ESPN, CLIC5, CDH23, PCDH15, WHRN, TMC1, TRIOBP (+20 more) |
| Sensory processing of sound by inner hair cells of the cochlea | 27 | 65.7× | 2e-42 | USH1C, ESPN, CLIC5, CDH23, CABP2, PCDH15, WHRN, TMC1 (+19 more) |
| Sensory processing of sound | 9 | 41.5× | 4e-11 | CDH23, CABP2, LHFPL5, MYO15A, MYO7A, STRC, MYH9, MYO3A (+1 more) |
| Sensory Perception | 9 | 12.8× | 2e-06 | CDH23, CABP2, LHFPL5, MYO15A, MYO7A, STRC, MYH9, MYO3A (+1 more) |
| Drug-mediated inhibition of MET activation | 2 | 170.4× | 0.002 | HGF, MET |
| MET activates STAT3 | 2 | 113.6× | 0.004 | HGF, MET |
| MET activates PTPN11 | 2 | 68.2× | 0.010 | HGF, MET |
| MET interacts with TNS proteins | 2 | 68.2× | 0.010 | HGF, MET |
| MET Receptor Activation | 2 | 56.8× | 0.012 | HGF, MET |
| MET activates PI3K/AKT signaling | 2 | 56.8× | 0.012 | HGF, MET |
| MET activates PTK2 signaling | 3 | 17.0× | 0.015 | COL11A2, HGF, MET |
| MET receptor recycling | 2 | 34.1× | 0.026 | HGF, MET |
| CD163 mediating an anti-inflammatory response | 2 | 34.1× | 0.026 | IL6, MYH9 |
| Gap junction assembly | 3 | 13.1× | 0.026 | GJB2, GJB3, GJB6 |
| MET activates RAS signaling | 2 | 31.0× | 0.027 | HGF, MET |
| MET activates RAP1 and RAC1 | 2 | 31.0× | 0.027 | HGF, MET |
| Sema4D in semaphorin signaling | 2 | 20.1× | 0.061 | MET, MYH9 |
| Activation of GABAB receptors | 2 | 17.9× | 0.072 | ADCY1, KCNJ10 |
| Defective SLC26A4 causes Pendred syndrome (PDS) | 1 | 170.4× | 0.074 | SLC26A4 |
| GABA B receptor activation | 2 | 16.2× | 0.079 | ADCY1, KCNJ10 |
| Mitochondrial tRNA aminoacylation | 2 | 15.5× | 0.079 | KARS1, NARS2 |
| Negative regulation of MET activity | 2 | 15.5× | 0.079 | HGF, MET |
| Semaphorin interactions | 2 | 11.8× | 0.119 | MET, MYH9 |
| Anti-inflammatory response favouring Leishmania parasite infection | 2 | 11.8× | 0.119 | ADCY1, MYH9 |
| Leishmania parasite growth and survival | 2 | 11.8× | 0.119 | ADCY1, MYH9 |
| Potassium transport channels | 1 | 56.8× | 0.144 | KCNJ10 |
| Oligomerization of connexins into connexons | 1 | 56.8× | 0.144 | GJB2 |
| Transport of connexins along the secretory pathway | 1 | 56.8× | 0.144 | GJB2 |
| Enzymatic degradation of dopamine by COMT | 1 | 56.8× | 0.144 | LRTOMT |
| GABA receptor activation | 2 | 9.5× | 0.150 | ADCY1, KCNJ10 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 85 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| sensory perception of sound | 46 | 54.6× | 8e-69 | TECTA, TMPRSS3, USH1C, ESPN, CLIC5, CDH23, CABP2, PCDH15 (+38 more) |
| auditory receptor cell stereocilium organization | 11 | 109.0× | 1e-18 | TECTA, CDH23, WHRN, TRIOBP, LHFPL5, PDZD7, TPRN, GRXCR1 (+3 more) |
| sensory perception of light stimulus | 8 | 176.2× | 5e-16 | USH1C, CDH23, PCDH15, WHRN, MYO7A, USH2A, USH1G, ADGRV1 |
| detection of mechanical stimulus involved in sensory perception of sound | 8 | 88.1× | 2e-12 | WHRN, TMC1, LHFPL5, PDZD7, PJVK, PTPRQ, STRC, ADGRV1 |
| equilibrioception | 5 | 141.6× | 7e-09 | USH1C, CDH23, PCDH15, MYO7A, USH1G |
| photoreceptor cell maintenance | 8 | 33.8× | 8e-09 | USH1C, CDH23, PCDH15, CIB2, ESRRB, USH2A, USH1G, ADGRV1 |
| inner ear receptor cell stereocilium organization | 6 | 59.5× | 4e-08 | USH1C, WHRN, OTOGL, GRXCR1, USH1G, ADGRV1 |
| inner ear receptor cell differentiation | 4 | 158.6× | 2e-07 | WHRN, PDZD7, USH2A, ADGRV1 |
| stereocilium maintenance | 3 | 148.7× | 3e-05 | TPRN, PJVK, ELMOD3 |
| cochlea development | 5 | 27.5× | 6e-05 | CDH23, GRXCR1, MYO7A, SLITRK6, SLC26A5 |
| visual perception | 9 | 8.4× | 6e-05 | CLIC5, CDH23, CABP2, MYO7A, USH2A, ADGRV1, SLITRK6, KCNJ10 (+1 more) |
| inner ear development | 5 | 22.0× | 1e-04 | PCDH15, ESRRB, GJB6, ROR1, ADGRV1 |
| inner ear morphogenesis | 5 | 17.7× | 4e-04 | USH1C, TMIE, MYO15A, USH1G, MYO6 |
| auditory receptor cell development | 3 | 66.1× | 4e-04 | TMC1, PDZD7, ELMOD3 |
| L-arabinose metabolic process | 2 | 198.3× | 1e-03 | OTOGL, OTOG |
| chloride transport | 4 | 21.4× | 0.001 | CLIC5, BSND, CLCNKA, SLC26A5 |
| inner ear auditory receptor cell differentiation | 3 | 42.5× | 0.001 | USH1C, USH2A, MYO6 |
| establishment of protein localization | 4 | 20.3× | 0.001 | WHRN, PDZD7, USH2A, ADGRV1 |
| auditory receptor cell morphogenesis | 2 | 99.1× | 0.004 | USH1C, SLITRK6 |
| regulation of actin filament length | 2 | 99.1× | 0.004 | EPS8, MYO3A |
| negative regulation of hydrogen peroxide-mediated programmed cell death | 2 | 99.1× | 0.004 | HGF, MET |
| actin filament-based movement | 3 | 28.3× | 0.004 | MYO7A, MYH9, MYO6 |
| barbed-end actin filament capping | 3 | 28.3× | 0.004 | TRIOBP, EPS8, RDX |
| establishment of endothelial barrier | 3 | 27.0× | 0.004 | MARVELD2, EDNRB, RDX |
| establishment of localization in cell | 5 | 9.4× | 0.004 | WHRN, PDZD7, ILDR1, GRXCR1, USH2A |
| maintenance of animal organ identity | 2 | 79.3× | 0.005 | USH2A, ADGRV1 |
| gap junction-mediated intercellular transport | 2 | 66.1× | 0.008 | GJB2, GJB6 |
| liver regeneration | 3 | 18.0× | 0.012 | SLC22A4, PNPT1, IL6 |
| gap junction assembly | 2 | 49.6× | 0.013 | GJB2, GJB6 |
| hepatocyte growth factor receptor signaling pathway | 2 | 49.6× | 0.013 | HGF, MET |
Therapeutics
Drug target analysis
Approved (phase 4): 8 · Phase ≥3: 9 · Phased (≥1): 10 · Undrugged: 68
Druggability breadth: 27 of 92 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| ESRRB | ESTRADIOL |
| GJB2 | KANAMYCIN |
| KARS1 | IMATINIB |
| RORA | TRETINOIN |
| S1PR2 | OZANIMOD |
| IL6 | PREDNISOLONE |
| MET | AFATINIB |
| MYO3A | AXITINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| MET | 95 | 4 |
| MYO3A | 9 | 4 |
| IL6 | 3 | 4 |
| ESRRB | 2 | 4 |
| RORA | 2 | 4 |
| ADCY1 | 2 | 3 |
| MSRB3 | 1 | 2 |
| GJB2 | 1 | 4 |
| KARS1 | 1 | 4 |
| S1PR2 | 1 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| ESTRADIOL | 4 | ESRRB |
| KANAMYCIN | 4 | GJB2 |
| IMATINIB | 4 | KARS1 |
| TRETINOIN | 4 | RORA |
| OZANIMOD | 4 | S1PR2 |
| PREDNISOLONE | 4 | IL6 |
| AFATINIB | 4 | MET |
| FEDRATINIB | 4 | MET |
| TIVOZANIB | 4 | MET |
| AXITINIB | 4 | MET, MYO3A |
| SORAFENIB | 4 | MET |
| NERATINIB | 4 | MET |
| INFIGRATINIB PHOSPHATE | 4 | MET |
| INFIGRATINIB | 4 | MET |
| PALBOCICLIB | 4 | MET |
| ENTRECTINIB | 4 | MET |
| DABRAFENIB | 4 | MET |
| CABOZANTINIB S-MALATE | 4 | MET |
| AFATINIB DIMALEATE | 4 | MET |
| CABOZANTINIB | 4 | MET |
| CERITINIB | 4 | MET |
| VANDETANIB | 4 | MET |
| BOSUTINIB | 4 | MET, MYO3A |
| CAPMATINIB | 4 | MET |
| TEPOTINIB | 4 | MET |
| BRIGATINIB | 4 | MET |
| ENSARTINIB | 4 | MET |
| PAZOPANIB | 4 | MET |
| NINTEDANIB | 4 | MET |
| SUNITINIB | 4 | MET, MYO3A |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 10.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| MET | 2,015 | Binding:2005, Functional:6, ADMET:4 |
| S1PR2 | 147 | Functional:78, Binding:69 |
| RORA | 115 | Binding:111, Functional:3, Unclassified:1 |
| MYO3A | 82 | Binding:82 |
| ADCY1 | 47 | Binding:34, Functional:12, ADMET:1 |
| KARS1 | 46 | Binding:45, ADMET:1 |
| ROR1 | 40 | Binding:40 |
| SLC26A4 | 37 | Binding:37 |
| SLC22A4 | 29 | Functional:26, ADMET:3 |
| ESRRB | 27 | Binding:19, Functional:8 |
| CDC14A | 19 | Binding:18, ADMET:1 |
| IL6 | 16 | Binding:16 |
| PCDH15 | 9 | Binding:9 |
| MSRB3 | 7 | Binding:6, ADMET:1 |
| WBP2 | 6 | Binding:6 |
| GJB2 | 5 | Binding:5 |
| PPIP5K2 | 4 | Binding:4 |
| HGF | 4 | Binding:4 |
| PTPRR | 3 | Binding:3 |
| MYO15A | 1 | Binding:1 |
| SERPINB6 | 1 | Binding:1 |
| RDX | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| MSRB3 | 1.8.4.12, 1.8.4.B3 | peptide-methionine (R)-S-oxide reductase, |
| KARS1 | 6.1.1.6 | lysine-tRNA ligase |
| PTPRQ | 3.1.3.48 | protein-tyrosine-phosphatase |
| PTPRR | 3.1.3.48 | protein-tyrosine-phosphatase |
| ROR1 | 2.7.10.1 | receptor protein-tyrosine kinase |
| PNPT1 | 2.7.7.8 | polyribonucleotide nucleotidyltransferase |
| ADCY1 | 4.6.1.1 | adenylate cyclase |
| NARS2 | 6.1.1.22 | asparagine-tRNA ligase |
| PPIP5K2 | 2.7.4.21, 2.7.4.24 | inositol-hexakisphosphate 5-kinase, diphosphoinositol-pentakisphosphate 1-kinase |
| MET | 2.7.10.1 | receptor protein-tyrosine kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| RORA | 115 |
| S1PR2 | 147 |
| MET | 2,015 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 78; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| ESTRADIOL | 4 | ESRRB |
| KANAMYCIN | 4 | GJB2 |
| IMATINIB | 4 | KARS1 |
| TRETINOIN | 4 | RORA |
| OZANIMOD | 4 | S1PR2 |
| PREDNISOLONE | 4 | IL6 |
| AFATINIB | 4 | MET |
| FEDRATINIB | 4 | MET |
| TIVOZANIB | 4 | MET |
| AXITINIB | 4 | MET, MYO3A |
| SORAFENIB | 4 | MET |
| NERATINIB | 4 | MET |
| INFIGRATINIB PHOSPHATE | 4 | MET |
| INFIGRATINIB | 4 | MET |
| PALBOCICLIB | 4 | MET |
| ENTRECTINIB | 4 | MET |
| DABRAFENIB | 4 | MET |
| CABOZANTINIB S-MALATE | 4 | MET |
| AFATINIB DIMALEATE | 4 | MET |
| CABOZANTINIB | 4 | MET |
| CERITINIB | 4 | MET |
| VANDETANIB | 4 | MET |
| BOSUTINIB | 4 | MET, MYO3A |
| CAPMATINIB | 4 | MET |
| TEPOTINIB | 4 | MET |
| BRIGATINIB | 4 | MET |
| ENSARTINIB | 4 | MET |
| PAZOPANIB | 4 | MET |
| NINTEDANIB | 4 | MET |
| SUNITINIB | 4 | MET, MYO3A |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 8 | ESRRB, GJB2, KARS1, RORA, S1PR2, IL6, MET, MYO3A |
| B | Phased (≥1) drug, not yet approved | 2 | MSRB3, ADCY1 |
| C | Druggable family + PDB, no drug | 6 | PTPRQ, PTPRR, ROR1, PPIP5K2, HGF, SLC26A5 |
| D | Druggable family + AlphaFold only, no drug | 8 | TMPRSS3, ILDR1, CEACAM16, MPZL2, SLC26A4, SLC22A4, CDC14A, NARS2 |
| E | Difficult family or no structure, no drug | 54 | TECTA, USH1C, ESPN, CLIC5, CDH23, CABP2, PCDH15, WHRN, OTOA, BSND (+44 more) |
Undrugged target profiles
68 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| ESPN | 0 | GJB2 |
| LOXHD1 | 0 | MYO3A |
| TMIE | 0 | GJB2 |
| GJB3 | 0 | GJB2 |
| GJB6 | 0 | GJB2 |
| MYO15A | 1 | GJB2 |
| SLC26A4 | 37 | GJB2 |
| EPS8L2 | 0 | MYO3A |
| HGF | 4 | MET |
| TECTA | 0 | — |
| TMPRSS3 | 0 | — |
| USH1C | 0 | — |
| CLIC5 | 0 | — |
| CDH23 | 0 | — |
| CABP2 | 0 | — |
| PCDH15 | 9 | — |
| WHRN | 0 | — |
| OTOA | 0 | — |
| BSND | 0 | — |
| TMC1 | 0 | — |
| TRIOBP | 0 | — |
| GIPC3 | 0 | — |
| CLDN14 | 0 | — |
| CLIC6 | 0 | — |
| LHFPL5 | 0 | — |
| CIB2 | 0 | — |
| PDZD7 | 0 | — |
| MARVELD2 | 0 | — |
| TPRN | 0 | — |
| OTOGL | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: TECTA, TMPRSS3, USH1C, ESPN, CLIC5, CDH23, CABP2, PCDH15, WHRN, OTOA, BSND, TMC1, TRIOBP, GIPC3, CLDN14, CLIC6, LHFPL5, CIB2, PDZD7, MARVELD2, LOXHD1, TPRN, OTOGL, MSRB3, ILDR1, GPSM2, PJVK, TMIE, GRXCR1, CEACAM16, GRXCR2, EPS8, ESRRB, MPZL2, GJB2, GJB3, GJB6, KARS1, MYO15A, MYO7A, OTOF, OTOG, SLC26A4, PTPRQ, PTPRR, ROR1, RORA, SLC22A4, TSPEAR, WBP2, BDP1, RIPOR2, STRC, CDC14A, DCDC2, EPS8L2, COL11A2, PNPT1, ADCY1, SLITRK6, ELMOD3, NARS2, SYNE4, TMEM132E, PPIP5K2, TBC1D24, S1PR2, GRAP, HGF, IL6, LMX1A, MET, MYO3A, MYO6, SERPINB6, SLC26A5, RDX