Usher syndrome

Summary

Usher syndrome (MONDO:0019501) is a disease (an umbrella term covering 5 Mondo subtypes) with 37 cohort genes and 18 clinical trials. The dominant Reactome pathway is Sensory processing of sound by outer hair cells of the cochlea (7 cohort genes).

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 37
• ClinVar variants: 562
• Phenotypes (HPO): 37
• Clinical trials: 18

Clinical features

Epidemiology

Prevalence records

10 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	4.53	Worldwide	Validated
Point prevalence	1-9 / 100 000	5	Denmark	Validated
Point prevalence	1-9 / 100 000	6.2	Germany	Validated
Point prevalence	1-9 / 100 000	6.2	United Kingdom	Validated
Point prevalence	1-9 / 100 000	3.6	Norway	Validated
Point prevalence	1-9 / 100 000	4.2	Spain	Validated
Point prevalence	1-9 / 100 000	3.5	Finland	Validated
Point prevalence	1-9 / 100 000	4.4	United States	Validated
Point prevalence	1-9 / 100 000	3.2	Colombia	Validated
Point prevalence	1-9 / 100 000	3	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0000505	Visual impairment	Very frequent (80-99%)
HP:0000512	Abnormal electroretinogram	Very frequent (80-99%)
HP:0000529	Progressive visual loss	Very frequent (80-99%)
HP:0000618	Blindness	Very frequent (80-99%)
HP:0000662	Nyctalopia	Very frequent (80-99%)
HP:0001123	Visual field defect	Very frequent (80-99%)
HP:0001751	Abnormal vestibular function	Very frequent (80-99%)
HP:0007703	Abnormality of retinal pigmentation	Very frequent (80-99%)
HP:0008568	Vestibular areflexia	Very frequent (80-99%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000545	Myopia	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0008499	High hypermetropia	Frequent (30-79%)
HP:0000360	Tinnitus	Occasional (5-29%)
HP:0000483	Astigmatism	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000670	Carious teeth	Occasional (5-29%)
HP:0000682	Abnormality of dental enamel	Occasional (5-29%)
HP:0000691	Microdontia	Occasional (5-29%)
HP:0000709	Psychosis	Occasional (5-29%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000738	Hallucinations	Occasional (5-29%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0001639	Hypertrophic cardiomyopathy	Occasional (5-29%)
HP:0002120	Cerebral cortical atrophy	Occasional (5-29%)
HP:0002194	Delayed gross motor development	Occasional (5-29%)
HP:0002312	Clumsiness	Occasional (5-29%)
HP:0003198	Myopathy	Occasional (5-29%)
HP:0003457	EMG abnormality	Occasional (5-29%)
HP:0007360	Aplasia/Hypoplasia of the cerebellum	Occasional (5-29%)
HP:0007994	Peripheral visual field loss	Occasional (5-29%)
HP:0008947	Floppy infant	Occasional (5-29%)
HP:0010780	Hyperacusis	Occasional (5-29%)
HP:0011025	Abnormality of cardiovascular system physiology	Occasional (5-29%)
HP:0011073	Abnormality of dental color	Occasional (5-29%)
HP:0031936	Delayed ability to walk	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Usher syndrome
Mondo ID	MONDO:0019501
MeSH	D052245
OMIM	276900
Orphanet	886
DOID	DOID:0050439
ICD-11	1452641873
NCIT	C85217
GARD	0007843
MedDRA	10063396
NORD	1816
Is cancer (heuristic)	no

Also known as: deafness-retinitis pigmentosa syndrome · dystrophia retinae pigmentosa-dysostosis syndrome · Graefe-Usher syndrome · Hallgren syndrome · retinitis pigmentosa-deafness syndrome · USH · ush · Usher’s syndrome

Data availability: 562 ClinVar variants · 78 ClinGen variant curations · 55 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Usher syndrome

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, long QT syndrome, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, Behcet disease, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Prader-Willi syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, polycystic ovary syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, Takayasu arteritis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, hypotrichosis-deafness syndrome, thalidomide embryopathy, trisomy X, trisomy 13, trisomy 18, umbilical cord ulceration-intestinal atresia syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, infantile spasms, Wolfram syndrome, epidermal nevus syndrome, digital anomalies-intellectual disability-short stature syndrome, intellectual disability-obesity-brain malformations-facial dysmorphism syndrome, Erdheim-Chester disease, Stevens-Johnson syndrome, CADDS, finger hyperphalangy - toe anomalies - severe pectus excavatum syndrome, ataxia - telangiectasia variant, growth retardation-mild developmental delay-chronic hepatitis syndrome, primary microcephaly-mild intellectual disability-young-onset diabetes syndrome, ferro-cerebro-cutaneous syndrome, dystonia-aphonia syndrome, microcephaly-complex motor and sensory axonal neuropathy syndrome, X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, intrauterine growth restriction-short stature-early adult-onset diabetes syndrome, pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa, familial chylomicronemia syndrome, caudal regression-sirenomelia spectrum, visceral heterotaxy, Holmes-Adie syndrome, microcephalic primordial dwarfism due to RTTN deficiency, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, Kallmann syndrome, Caroli syndrome, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability, microlissencephaly-micromelia syndrome, branchiootic syndrome, Plummer-Vinson syndrome, Cushing syndrome, McCune-Albright syndrome, Meckel syndrome, SUNCT syndrome, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, congenital myasthenic syndrome, Loeys-Dietz syndrome, Alport syndrome, schisis association, Tolosa-Hunt syndrome, iridocorneal endothelial syndrome, Noonan syndrome, short fifth metacarpals-insulin resistance syndrome, progressive supranuclear palsy, benign exophthalmos syndrome, Sandifer syndrome, global developmental delay-osteopenia-ectodermal defect syndrome, tubular renal disease-cardiomyopathy syndrome, angioosteohypotrophic syndrome, 6q terminal deletion syndrome, Axenfeld-Rieger syndrome, peroxisome biogenesis disorder, ectodermal dysplasia syndrome, Seckel syndrome, Sotos syndrome, Stickler syndrome, pelvis syndrome, Susac syndrome, ischio-vertebral syndrome, BRESEK syndrome, Turner syndrome, obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome, CREST syndrome, Sheehan syndrome, polymyalgia rheumatica, autoinflammatory syndrome, neuroleptic malignant syndrome, pituitary stalk interruption syndrome, monosomy 13q34, ring chromosome 13, 48,XXXY syndrome, 49,XXXXY syndrome, hereditary continuous muscle fiber activity, Eisenmenger syndrome, Robinow syndrome, Ehlers-Danlos syndrome, hypoplastic right heart syndrome, shone complex, 48,XYYY syndrome, subcortical band heterotopia, complex regional pain syndrome type 2, faciodigitogenital syndrome, neoplastic syndrome, paraneoplastic syndrome, post-infectious syndrome, Achard-Thiers syndrome, acral dysostosis dyserythropoiesis syndrome, agnathia-microstomia-synotia, Aksu von Stockhausen syndrome, Aloi Tomasini Isaia syndrome, temporomandibular joint dysfunction syndrome, Apert-like polydactyly syndrome, arakawa syndrome 2, arena syndrome, Arnold stickler bourne syndrome, baetz-greenwalt syndrome, bagatelle Cassidy syndrome, baker Vinters syndrome, bobble-head doll syndrome, Boerhaave syndrome, Cantu Sanchez-Corona Fragoso syndrome, Cantu Sanchez-Corona Hernandez syndrome, carbon baby syndrome, Carnevale hernandez castillo syndrome, Cartwright Nelson Fryns syndrome, Charles bonnet syndrome, Parinaud syndrome, corticobasal degeneration disorder, hair defect with photosensitivity and intellectual disability syndrome, AIDS dysmorphic syndrome, congenital acardia, acute lymphoblastic leukemia congenital sporadic aniridia, aglossia and situs inversus, agyria pachygyria polymicrogyria, agyria-pachygyria type 1, Ahumada Del Castillo syndrome, alopecia congenita keratosis palmoplantaris, alpha-mannosidosis type 1, aluminosis, Mauriac syndrome, ankle defects short stature, ankyloblepharon filiforme imperforate anus, annular constricting bands, anophthalmia cleft palate micrognathia, anophthalmia esophageal atresia cryptorchidism, anotia facial palsy cardiac defect, aortic dissection lentiginosis, childhood aortic valve stenosis, arthrogryposis IUGR thoracic dystrophy, arthrogryposis multiplex congenita CNS calcification, arthrogryposis spinal muscular atrophy, asternia, atlanto-axial fusion, atrophoderma of Pierini and Pasini, Barnicoat Baraitser syndrome, Basedow’s coma, BD syndrome, Beardwell syndrome, bhaskar jagannathan syndrome, bidirectional tachycardia, bilirubin induced brain injury in the newborn, blepharo naso facial syndrome van Maldergem type, bone dysplasia corpus callosum agenesis, brachydactyly absence of distal phalanges, brachydactyly anonychia, brachydactyly small stature face anomalies, brachydactyly tibial hypoplasia, brittle bone syndrome lethal type, bronchiectasis oligospermia, Brunsting-Perry syndrome, bruyn scheltens syndrome, burn goodship syndrome, camptodactyly joint contractures and facial skeletal dysplasia, camptodactyly vertebral fusion, Cantu Sanchez-Corona Garcia-Cruz syndrome, cardiac hydatid cysts with intracavitary expansion, cardioencephalomyopathy, cardiofacial syndrome short limbs, cardiomelic syndrome stratton Koehler type, cardiomyopathy and deafness due to tRNA lysine gene mutation, cardiomyopathy diabetes deafness, cardiomyopathy hypogonadism collagenoma syndrome, cardiomyopathy hypogonadism metabolic anomalies, cardiomyopathy spherocytosis, carpo tarsal osteolysis recessive, autosomal dominant cataract, cataract skeletal anomalies, cennamo gangemi syndrome, cerebellar agenesis, cerebello-olivary atrophy, cerebral calcification cerebellar hypoplasia, cerebral calcifications opalescent teeth phosphaturia, oculo digital syndrome, chondrodysplasia, choreoacanthocytosis amyotrophic, chorioretinopathy dominant form microcephaly, Christian Demyer Franken syndrome, Christian Johnson angenieta syndrome, chromosome 3 duplication syndrome, chronic demyelinizing neuropathy with IgM monoclonal, ciliary dyskinesia-bronchiectasis, circumscribed cutaneous aplasia of the vertex, circumscribed disseminated keratosis Jadassohn lew type, cleft lip and palate malrotation cardiopathy, cleft lip and/or palate with mucous cysts of lower, cleft lip palate dysmorphism kumar type, cleft lip palate intellectual disability corneal opacity, cleft lip palate oligodontia syndactyly pili torti, cleft lip palate pituitary deficiency, cleft lip palate-tetraphocomelia, cleft lower lip cleft lateral canthi chorioretinal, cleft palate cardiac defect ectrodactyly, cleft palate colobomata radial synostosis deafness, cleft palate heart disease polydactyly absent tibia, cleft tongue, coarse face hypotonia constipation, Cohen Lockood Wyborney syndrome, type 2 collagenopathy, Collins-Sakati syndrome, coloboma porencephaly hydronephrosis, colobomata unilobar lung heart defect, colonic malakoplakia, Colver Steer Godman syndrome, Combarros Calleja Leno syndrome, complement receptor deficiency, congenital absence of the sternocleidomastoid muscle, congenital amputation, congenital aneurysms of the great vessels, congenital articular rigidity, congenital benign spinal muscular atrophy dominant, congenital cardiovascular shunt, congenital contractures, congenital craniosynostosis maternal hyperthyroiditis, congenital cystic eye, congenital heart disease ptosis hypodontia craniostosis, congenital heart disease radio ulnar synostosis intellectual disability, congenital mumps, congenital stenosis of cervical medullary canal, Dennis-Fairhurst-Moore syndrome, congenital unilateral pulmonary hypoplasia, congenital vagal hyperreflexivity, Cormier Rustin Munnich syndrome, corneal crystals myopathy neuropathy, corneal dystrophy ichthyosis microcephaly intellectual disability, corneal dystrophy pigmentary anomaly malabsorption, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cortada Koussef Matsumoto syndrome, Cortes Lacassie syndrome, craniofacial and skeletal defects, craniofacial dysostosis arthrogryposis progeroid appearance, craniofrontonasal syndrome Teebi type, craniostenosis with congenital heart disease intellectual disability, crawfurd syndrome, cutis gyratum acanthosis nigricans craniosynostosis, cutis laxa osteoporosis, Davenport-Donlan syndrome, Davis Lafer syndrome, de Hauwere Leroy adriaenssens syndrome, deafness conductive stapedial ear malformation facial palsy, deafness goiter stippled epiphyses, deafness hypospadias metacarpal and metatarsal syndrome, deafness mesenteric diverticula of small bowel neuropathy, deafness peripheral neuropathy arterial disease, deafness progressive cataract autosomal dominant, dermatocardioskeletal syndrome boronne type, dextrocardia with situs inversus, diabetes persistent mullerian ducts, diaphragmatic agenesis radial aplasia omphalocele, diaphragmatic hernia exomphalos corpus callosum agenesis, diaphragmatic hernia upper limb defects, die Smulders droog van dijk syndrome, diomedi bernardi placidi syndrome, diphallus rachischisis imperforate anus, distichiasis heart congenital anomalies, double discordia, double uterus-hemivagina-renal agenesis, Drachtman Weinblatt Sitarz syndrome, Duker-Weiss-Siber syndrome, duodenal atresia tetralogy of fallot, duplication of leg mirror foot, duplication of the thumb unilateral biphalangeal, dupont sellier chochillon syndrome, dwarfism bluish sclerae, dwarfism deafness retinitis pigmentosa, dwarfism lethal type advanced bone age, dwarfism thin bones multiple fractures, dysmorphism cleft palate loose skin, Eagle syndrome, ectrodactyly cardiopathy dysmorphism, Elliott ludman Teebi syndrome, enamel hypoplasia cataract hydrocephaly, encephalocele anencephaly, enchondromatosis dwarfism deafness, Engelhard Yatziv syndrome, enlarged vestibular aqueduct syndrome, epidermal nevus vitamin D resistant rickets, epimetaphyseal dysplasia cataract, epiphyseal dysplasia dysmorphism camptodactyly, esophageal atresia coloboma talipes, extrasystoles short stature hyperpigmentation microcephaly, facial clefting corpus callosum agenesis, facio digito genital syndrome recessive form, facio skeletal genital syndrome rippberger type, familial capillaro-venous leptomeningeal angiomatosis, Dursun syndrome, Faye-Petersen-Ward-Carey syndrome, feigenbaum Bergeron syndrome, Feingold trainer syndrome, fetal brain disruption sequence, fetal enterovirus syndrome, fetal parainfluenza virus type 3 syndrome, fetal phenothiazine syndrome, fibromatosis multiple non ossifying, fibula aplasia complex brachydactyly, fibular hypoplasia scapulo pelvic dysplasia absent, Fitz-Hugh-Curtis syndrome, focal alopecia congenital megalencephaly, focal or multifocal malformations in neuronal migration, foix chavany Marie syndrome, Fontaine farriaux blanckaert syndrome, Fraser Jequier Chen syndrome, Freiberg disease, Friedman Goodman syndrome, frontonasal malformation cloacal exstrophy, frontonasal dysplasia Klippel feil syndrome, frontonasal dysplasia phocomelic upper limbs, Fryns Fabry Remans syndrome, Fryns Smeets Thiry syndrome, Fuchs atrophia gyrata chorioideae et retinae, Fukuda-Miyanomae-Nakata syndrome, Fuqua Berkovitz syndrome, Garret-Tripp syndrome, gas bloat syndrome, Gaucher ichthyosis restrictive dermopathy, gershinibaruch Leibo syndrome, Ghose-Sachdev-Kumar syndrome, gigantism advanced bone age hoarse cry, glossopalatine ankylosis micrognathia ear anomalies, goldstein hutt syndrome, goniodysgenesis intellectual disability short stature, green sandford davison syndrome, grix Blankenship Peterson syndrome, Ho-Kaufman-McAlister syndrome, Jaffer-Beighton syndrome, Judge Misch wright syndrome, Kashani-Strom-Utley syndrome, Kasznica-Carlson-Coppedge syndrome, Katsantoni-Papadakou-Lagoyanni syndrome, Kocher-debre-Semelaigne syndrome, Koone-Rizzo-Elias syndrome, Kozlowski Brown Hardwick syndrome, Kozlowski Ouvrier syndrome, Kozlowski Rafinski Klicharska syndrome, Kozlowski Warren Fisher syndrome, Krauss Herman Holmes syndrome, Krieble Bixler syndrome, Kuster Majewski Hammerstein syndrome, Kuster syndrome, Laugier-Hunziker syndrome, Laurence-Prosser-Rocker syndrome, le Marec-Bracq-Picaud syndrome, levator syndrome, Marinesco-Sjogren-like syndrome, Milner-Khallouf-Gibson syndrome, radio-digito-facial dysplasia, Seckel like syndrome majoor-krakauer type, neonatal aspiration syndrome, muscular fibrosis multifocal obstructed vessels, short stature contractures hypotonia, Alice in Wonderland syndrome, megacystis-microcolon-intestinal hypoperistalsis syndrome, Basilicata-Akhtar syndrome, Liberfarb syndrome, craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome, cardiac, facial, and digital anomalies with developmental delay, fibrosis, neurodegeneration, and cerebral angiomatosis, Duane anomaly-myopathy-scoliosis syndrome, congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, acute radiation syndrome, monoclonal mast cell activation syndrome, oculocerebrodental syndrome, syndromic congenital sodium diarrhea, congenital brachyesophagus-intrathoracic stomach-vertebral anomalies syndrome, intellectual disability-cardiac anomalies-short stature-joint laxity syndrome, intrauterine growth restriction-congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome, frontonasal dysplasia-bifid nose-upper limb anomalies syndrome, microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome, diaphragmatic hernia-short bowel-asplenia syndrome, warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome, Cramp-fasciculation syndrome, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, blepharophimosis-intellectual disability syndrome/genitopatellar overlap syndrome, CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome, cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome, KLHL7-related Bohring-Opitz-like syndrome, KLHL7-related cold-induced sweating-like syndrome, KAT6B-related multiple congenital anomalies syndrome, oculogastrointestinal-neurodevelopmental syndrome, spastic paraparesis-cataracts-speech delay syndrome, Ruzicka-Goerz-Anton syndrome, Sammartino-Decreccio syndrome, Samson-Gardner syndrome, Samson-Viljoen syndrome, Sanderson-Fraser syndrome, Sandhaus-Ben-Ami syndrome, prostatic malacoplakia associated with prostatic abscess, Saul-Wilkes-Stevenson syndrome, macrogyria, pseudobulbar palsy and intellectual disability, Schwartz-Cohen-addad-Lambert syndrome, Schlegelberger-Grote syndrome, Schrander-stumpel-Theunissen-Hulsmans syndrome, Saal-Bulas syndrome, Sackey-Sakati-Aur syndrome, Slti-Salem syndrome, Zerres Rietschel Majewski syndrome, Zazam Sheriff Phillips syndrome, Zadik-Barak-Levin syndrome, weinstein kliman scully syndrome, thickened earlobes with conductive deafness from incus-stapes abnormalities, ichthyosis linearis circumflexa, infantile striato thalamic degeneration, Landy-Donnai syndrome, merlob grunebaum reisner syndrome, Pavone Fiumara Rizzo syndrome, pfeiffer rockelein syndrome, Pfeiffer Tietze Welte syndrome, phosphoribosylpyrophosphate synthetase deficiency, piepkorn karp hickok syndrome, podder-tolmie syndrome, pointer syndrome, richieri-costa guion-almeida cohen syndrome, Rubinstein Taybi like syndrome, ruvalcaba churesigaew myhre syndrome, short limb dwarf lethal colavita kozlowski type, Mallory-Weiss syndrome, superior vena cava syndrome, piriformis syndrome, engraftment syndrome, Adams-Stokes syndrome, Leriche syndrome, multiple organ dysfunction syndrome, posterior leukoencephalopathy syndrome, cardio-renal syndrome, Rahman syndrome, X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, Lopes-Maciel-Rodan syndrome, Stankiewicz-Isidor syndrome, Skraban-Deardorff syndrome, joint laxity, short stature, and myopia, Sweeney-Cox syndrome, Alkuraya-Kucinskas syndrome, Jaberi-Elahi syndrome, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, hearing impairment and infertile male syndrome, cardiocutaneous syndrome, neonatal diabetes, congenital sensorineural hearing loss and congenital cataracts, cardioectodermal syndrome, cannabinoid hyperemesis syndrome, retrograde cricopharyngeus dysfunction, Zinner syndrome, retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome, IFAP syndrome, DICER1-related tumor predisposition, Roberts-SC phocomelia syndrome, carcinoid syndrome, Bonnevie-Ullrich syndrome, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, RNU4ATAC spectrum disorder, syndromic congenital heart disease, hand-foot syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, gastrointestinal defects and immunodeficiency syndrome 1, achalasia-alacrima syndrome, black locks with albinism and deafness syndrome, Birt-Hogg-Dube syndrome, trigeminal trophic syndrome, developmental and/or epileptic encephalopathy with spike-wave activation in sleep, syndromic microspherophakia, painful legs and moving toes syndrome, congenital aphakia-iris hypoplasia-microphthalmia-microcornea syndrome, hereditary persistence of fetal hemoglobin-intellectual disability syndrome, developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome, primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome, post-cardiac arrest syndrome, early-onset obesity-hyperphagia-severe developmental delay syndrome, hereditary alpha tryptasemia syndrome, KINSSHIP syndrome, developmental delay, hypotrophy, and dysmorphic features without moebius syndrome, breast implant illness, cataracts, hearing impairment, nephrotic syndrome, and enterocolitis, craniosynostosis-facial dysmorphism-chiari-1 malformation-developmental and language delay syndrome, MYT1L-related developmental delay-intellectual disability-obesity syndrome, Houge-Janssens syndrome, xerosis and growth failure with immune and pulmonary dysfunction syndrome, Fliedner-Zweier syndrome, Lui-Jee-Baron syndrome, Long-Olsen-Distelmaier syndrome, Tan-Almurshedi syndrome, diabetes, deafness, developmental delay, and short stature syndrome, Alfadhel syndrome, Hoxha-Aliu syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, congenital insensitivity to pain syndrome, Marsili type, Yuksel-Vogel-Bauer syndrome, polydactyly-macrocephaly syndrome, pyoderma gangrenosum-acne-hidradenitis suppurativa-ankylosing spondylitis syndrome, psoriatic arthritis-pyoderma gangrenosum-acne-hidradenitis suppurativa syndrome, megalencephaly-polydactyly syndrome, Leigh syndrome, mitochondrial, auroneurodental syndrome, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, Grisel syndrome, arterial tortuosity-bone fragility syndrome, dialysis disequilibrium syndrome, brain abnormalities-severe developmental delay-facial dysmorphism-intellectual disability syndrome due to MEF2C mutation, Kariminejad neurodevelopmental syndrome, myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, brain malformation renal syndrome, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, Morimoto-Ryu-Malicdan neuromuscular syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, Pan-Chung-Bellen syndrome, telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature, Muggenthaler-Chowdhury-Chioza syndrome, Tayoun-Maawali syndrome, ragopathy, cardiovascular-kidney-metabolic syndrome, craniofaciocardiohepatic syndrome, FICUS syndrome, Li-Takada-Miyake syndrome, Guillouet-Gordon syndrome, ICHAD syndrome, cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome, RAC2-related combined immunodeficiency-bronchiectasis-cancer-predisposing syndrome, oculovertebral syndrome, Alsahan-Harris syndrome, Ververi-Brady syndrome, Dursun-Ozgul neurodevelopmental syndrome, immune dysregulation, neurodevelopmental defects, and colitis, Harel-Tora neurodevelopmental syndrome, Valence-Farazi cerebellar ataxia syndrome, dyschromatosis, ichthyosis, deafness, and atopic disease, Ramond-Elliott neurodevelopmental syndrome, STAD syndrome, craniosynostosis-scoliosis syndrome, loin pain hematuria syndrome, IRF6-related condition, linkeropathy, NDUFB11-related disorders, CRYAB-related myofibrillar myopathy-cataract-cardiomyopathy spectrum disorder, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy, antiphospholipid syndrome

Subtypes (5): Usher syndrome type 1, retinitis pigmentosa-deafness syndrome, Usher syndrome type 2, Usher syndrome type 3, Usher syndrome, type 4

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

562 retrieved; paginated sample, class counts are floors:

183 pathogenic/likely pathogenic, 151 pathogenic, 89 likely pathogenic, 67 conflicting classifications of pathogenicity, 49 uncertain significance, 11 likely benign, 7 benign, 4 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098772	NM_032119.4(ADGRV1):c.9749-2del	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1321451	NM_032119.4(ADGRV1):c.7130G>A (p.Arg2377Gln)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1354042	NM_032119.4(ADGRV1):c.5944dup (p.Ser1982fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1369585	NM_032119.4(ADGRV1):c.16041dup (p.Thr5348fs)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
1374682	NM_032119.4(ADGRV1):c.12211C>T (p.Arg4071Ter)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1447059	NM_032119.4(ADGRV1):c.6610C>T (p.Gln2204Ter)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804842	NM_032119.4(ADGRV1):c.18646del (p.Ala6216fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1878392	NM_032119.4(ADGRV1):c.13273_13280del (p.Leu4425fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2125215	NM_032119.4(ADGRV1):c.3364dup (p.Ser1122fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2503073	NM_032119.4(ADGRV1):c.2812C>T (p.Gln938Ter)	ADGRV1	Pathogenic	criteria provided, single submitter
2503083	NM_032119.4(ADGRV1):c.11938C>T (p.Gln3980Ter)	ADGRV1	Pathogenic	criteria provided, single submitter
2503089	NM_032119.4(ADGRV1):c.9439C>T (p.Arg3147Ter)	ADGRV1	Pathogenic	criteria provided, single submitter
2503090	NM_032119.4(ADGRV1):c.227del (p.Gly76fs)	ADGRV1	Pathogenic	criteria provided, single submitter
2503093	NM_032119.4(ADGRV1):c.14329C>T (p.Gln4777Ter)	ADGRV1	Pathogenic	criteria provided, single submitter
3063863	NM_032119.4(ADGRV1):c.10570C>T (p.Gln3524Ter)	ADGRV1	Pathogenic	criteria provided, single submitter
3896376	NM_032119.4(ADGRV1):c.3438C>G (p.Tyr1146Ter)	ADGRV1	Pathogenic	criteria provided, single submitter
3902720	NM_032119.4(ADGRV1):c.8785_8788delinsTTACCATGTAAT (p.Thr2930fs)	ADGRV1	Pathogenic	criteria provided, single submitter
402257	NM_032119.4(ADGRV1):c.2898G>A (p.Glu966=)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438168	NM_032119.4(ADGRV1):c.12798T>A (p.Tyr4266Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
438170	NM_032119.4(ADGRV1):c.17314C>T (p.Arg5772Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
438171	NM_032119.4(ADGRV1):c.8807C>G (p.Ser2936Ter)	ADGRV1	Pathogenic	criteria provided, single submitter
46275	NM_032119.4(ADGRV1):c.14973-2A>G	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4688311	NM_032119.4(ADGRV1):c.11055T>A (p.Tyr3685Ter)	ADGRV1	Pathogenic	criteria provided, single submitter
4847671	NC_000005.9:g.(90159675_90261231)_(90398158_90445846)del	ADGRV1	Pathogenic	criteria provided, single submitter
562081	NM_032119.4(ADGRV1):c.1055C>T (p.Pro352Leu)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
635159	NM_032119.4(ADGRV1):c.14315C>G (p.Ser4772Ter)	ADGRV1	Pathogenic	no assertion criteria provided
6798	NM_032119.4(ADGRV1):c.6901C>T (p.Gln2301Ter)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
817512	NM_032119.4(ADGRV1):c.2864C>A (p.Ser955Ter)	ADGRV1	Pathogenic	criteria provided, multiple submitters, no conflicts
866110	NM_032119.4(ADGRV1):c.12697dup (p.Ser4233fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866710	NM_032119.4(ADGRV1):c.16436del (p.Asn5479fs)	ADGRV1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 58 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
USH1C	Orphanet:231169	Usher syndrome type 1
USH1C	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
USH2A	Orphanet:231178	Usher syndrome type 2
USH2A	Orphanet:791	Retinitis pigmentosa
CLRN1	Orphanet:231183	Usher syndrome type 3
CLRN1	Orphanet:791	Retinitis pigmentosa
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
CABP4	Orphanet:714070	Incomplete congenital stationary night blindness, Schubert-Bornschein type
CABP4	Orphanet:98784	Sleep-related hypermotor epilepsy
HDAC6	Orphanet:163966	X-linked dominant chondrodysplasia, Chassaing-Lacombe type
PCDH15	Orphanet:231169	Usher syndrome type 1
PCDH15	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
USH1G	Orphanet:231169	Usher syndrome type 1
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
ADGRV1	Orphanet:231178	Usher syndrome type 2
ADGRV1	Orphanet:36387	Genetic epilepsy with febrile seizure plus
COCH	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL4A4	Orphanet:653722	Digenic Alport syndrome
COL4A4	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A4	Orphanet:88919	Autosomal recessive Alport syndrome
CRX	Orphanet:1872	Cone rod dystrophy
CRX	Orphanet:65	Leber congenital amaurosis
CRX	Orphanet:791	Retinitis pigmentosa
ARSG	Orphanet:231183	Usher syndrome type 3
CIB2	Orphanet:231169	Usher syndrome type 1
CIB2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CCDC40	Orphanet:244	Primary ciliary dyskinesia
PDZD7	Orphanet:231178	Usher syndrome type 2
KIF11	Orphanet:2526	Microcephaly-lymphedema-chorioretinopathy syndrome
MYO7A	Orphanet:231169	Usher syndrome type 1
MYO7A	Orphanet:231178	Usher syndrome type 2
MYO7A	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MYO7A	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
ATP6V1B1	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
PDE6A	Orphanet:791	Retinitis pigmentosa
SERPINB6	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
PROM1	Orphanet:1872	Cone rod dystrophy
PROM1	Orphanet:319640	Retinal macular dystrophy type 2
PROM1	Orphanet:791	Retinitis pigmentosa
PROM1	Orphanet:827	Stargardt disease
BBS1	Orphanet:110	Bardet-Biedl syndrome
BBS1	Orphanet:791	Retinitis pigmentosa
PRPH2	Orphanet:1872	Cone rod dystrophy

Cohort genes → proteins

37 cohort genes, 33 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	37

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BPNT1	HGNC:1096	ENSG00000162813	O95861	3’(2’),5’-bisphosphate nucleotidase 1	clinvar
USH1C	HGNC:12597	ENSG00000006611	Q9Y6N9	Harmonin	clinvar
USH2A	HGNC:12601	ENSG00000042781	O75445	Usherin	clinvar
CLRN1	HGNC:12605	ENSG00000163646	P58418	Clarin-1	clinvar
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	clinvar
CABP4	HGNC:1386	ENSG00000175544	P57796	Calcium-binding protein 4	clinvar
HDAC6	HGNC:14064	ENSG00000094631	Q9UBN7	Protein deacetylase HDAC6	clinvar
PCDH15	HGNC:14674	ENSG00000150275	Q96QU1	Protocadherin-15	clinvar
USH1G	HGNC:16356	ENSG00000182040	Q495M9	pre-mRNA splicing regulator USH1G	clinvar
WHRN	HGNC:16361	ENSG00000095397	Q9P202	Whirlin	clinvar
OTOA	HGNC:16378	ENSG00000155719	Q7RTW8	Otoancorin	clinvar
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	clinvar
CEP250	HGNC:1859	ENSG00000126001	Q9BV73	Centrosome-associated protein CEP250	clinvar
OTOP2	HGNC:19657	ENSG00000183034	Q7RTS6	Proton channel OTOP2	clinvar
C10orf105	HGNC:20304	ENSG00000214688	Q8TEF2	Uncharacterized protein C10orf105	clinvar
COCH	HGNC:2180	ENSG00000100473	O43405	Cochlin	clinvar
COL4A4	HGNC:2206	ENSG00000081052	P53420	Collagen alpha-4(IV) chain	clinvar
CRX	HGNC:2383	ENSG00000105392	O43186	Cone-rod homeobox protein	clinvar
ARSG	HGNC:24102	ENSG00000141337	Q96EG1	Arylsulfatase G	clinvar
SLC9B1	HGNC:24244	ENSG00000164037	Q4ZJI4	Sodium/hydrogen exchanger 9B1	clinvar
CIB2	HGNC:24579	ENSG00000136425	O75838	Calcium and integrin-binding family member 2	clinvar
CCDC40	HGNC:26090	ENSG00000141519	Q4G0X9	Coiled-coil domain-containing protein 40	clinvar
PDZD7	HGNC:26257	ENSG00000186862	Q9H5P4	PDZ domain-containing protein 7	clinvar
FMC1	HGNC:26946	ENSG00000164898	Q96HJ9	Protein FMC1 homolog	clinvar
DGKQ	HGNC:2856	ENSG00000145214	P52824	Diacylglycerol kinase theta	clinvar
SIAH2-AS1	HGNC:40526	ENSG00000244265		SIAH2 and CLRN1 antisense RNA 1	clinvar
USH2A-AS2	HGNC:40605	ENSG00000233620		USH2A antisense RNA 2	clinvar
USH2A-AS1	HGNC:40606	ENSG00000236292		USH2A antisense RNA 1	clinvar
GUCA1ANB-GUCA1A	HGNC:56129	ENSG00000290147		GUCA1ANB-GUCA1A readthrough	clinvar
KIF11	HGNC:6388	ENSG00000138160	P52732	Kinesin-like protein KIF11	clinvar
MYO7A	HGNC:7606	ENSG00000137474	Q13402	Unconventional myosin-VIIa	clinvar
ATP6V1B1	HGNC:853	ENSG00000116039	P15313	V-type proton ATPase subunit B, kidney isoform	clinvar
PDE6A	HGNC:8785	ENSG00000132915	P16499	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha	clinvar
SERPINB6	HGNC:8950	ENSG00000124570	P35237	Serpin B6	clinvar
PROM1	HGNC:9454	ENSG00000007062	O43490	Prominin-1	clinvar
BBS1	HGNC:966	ENSG00000174483	Q8NFJ9	BBSome complex member BBS1	clinvar
PRPH2	HGNC:9942	ENSG00000112619	P23942	Peripherin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BPNT1	3’(2’),5’-bisphosphate nucleotidase 1	Phosphatase that converts 3’(2’)-phosphoadenosine 5’-phosphate (PAP) to AMP and inositol 1,4-bisphosphate (Ins(1,4)P2) to inositol 4-phosphate.
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.
USH2A	Usherin	Involved in hearing and vision as member of the USH2 complex.
CLRN1	Clarin-1	May have a role in the excitatory ribbon synapse junctions between hair cells and cochlear ganglion cells and presumably also in analogous synapses within the retina.
CDH23	Cadherin-23	Cadherins are calcium-dependent cell adhesion proteins.
CABP4	Calcium-binding protein 4	Involved in normal synaptic function through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals and in auditory transmission.
HDAC6	Protein deacetylase HDAC6	Deacetylates a wide range of non-histone substrates.
PCDH15	Protocadherin-15	Calcium-dependent cell-adhesion protein.
USH1G	pre-mRNA splicing regulator USH1G	Plays a role in pre-mRNA splicing by regulating the release and transfer of U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complexes from their assembly site in Cajal bodies to nuclear speckles, thereby contributing to the assemb…
WHRN	Whirlin	Involved in hearing and vision as member of the USH2 complex.
OTOA	Otoancorin	May act as an adhesion molecule.
ADGRV1	Adhesion G-protein coupled receptor V1	G-protein coupled receptor which has an essential role in the development of hearing and vision.
CEP250	Centrosome-associated protein CEP250	Plays an important role in centrosome cohesion during interphase.
OTOP2	Proton channel OTOP2	Proton-selective ion channel open at neutral pH.
COCH	Cochlin	Plays a role in the control of cell shape and motility in the trabecular meshwork.
COL4A4	Collagen alpha-4(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
CRX	Cone-rod homeobox protein	Transcription factor that binds and transactivates the sequence 5’-TAATC[CA]-3’ which is found upstream of several photoreceptor-specific genes, including the opsin genes.
ARSG	Arylsulfatase G	Displays arylsulfatase activity at acidic pH towards artificial substrates, such as p-nitrocatechol sulfate and also, but with a lower activity towards p-nitrophenyl sulfate and 4-methylumbelliferyl sulfate.
SLC9B1	Sodium/hydrogen exchanger 9B1	Sperm-specific Na(+)/H(+) exchanger involved in intracellular pH regulation of spermatozoa.
CIB2	Calcium and integrin-binding family member 2	Calcium- and integrin-binding protein that plays a role in intracellular calcium homeostasis.
CCDC40	Coiled-coil domain-containing protein 40	Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella.
PDZD7	PDZ domain-containing protein 7	In cochlear developing hair cells, essential in organizing the USH2 complex at stereocilia ankle links.
FMC1	Protein FMC1 homolog	Plays a role in the assembly/stability of the mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V).
DGKQ	Diacylglycerol kinase theta	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
KIF11	Kinesin-like protein KIF11	Motor protein required for establishing a bipolar spindle and thus contributing to chromosome congression during mitosis.
MYO7A	Unconventional myosin-VIIa	Myosins are actin-based motor molecules with ATPase activity.
ATP6V1B1	V-type proton ATPase subunit B, kidney isoform	Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
PDE6A	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha	Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP.
SERPINB6	Serpin B6	May be involved in the regulation of serine proteinases present in the brain or extravasated from the blood.
PROM1	Prominin-1	May play a role in cell differentiation, proliferation and apoptosis.
BBS1	BBSome complex member BBS1	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
PRPH2	Peripherin-2	Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure.

Protein-family classification

Druggable: 7 · Difficult: 8 · Unknown: 22 · Druggable fraction: 0.19

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
Phosphatase	2	4.5×	0.323
Scaffold/PPI	5	2.3×	0.323
Transporter	1	2.1×	0.882
Other/Unknown	22	1.1×	0.882
Antibody/Immunoglobulin	1	0.8×	0.948
Kinase	1	0.8×	0.948
Transcription factor	3	0.7×	0.948
GPCR	1	0.7×	0.948
Enzyme (other)	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BPNT1	Phosphatase	yes	3.1.3.7	Inositol_monophosphatase-like, Inositol_monophosphatase_CS, Inositol_monoP_metal-BS
USH1C	Scaffold/PPI	no		PDZ, Harmonin_N, PDZ_sf
USH2A	Antibody/Immunoglobulin	yes		Laminin_G, LE_dom, FN3_dom
CLRN1	Other/Unknown	no		Clarin
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
CABP4	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
HDAC6	Transcription factor	no	3.5.1.98	HDACs, Znf_UBP, Znf_RING/FYVE/PHD
PCDH15	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
USH1G	Scaffold/PPI	no		SAM, Ankyrin_rpt, SAM/pointed_sf
WHRN	Scaffold/PPI	no		PDZ, Whirlin_HN-like_dom2, PDZ_sf
OTOA	Other/Unknown	no		Stereocilin-rel
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP
CEP250	Other/Unknown	no		Rootletin-like_CC, CEP250_CC
OTOP2	Other/Unknown	no		Otopetrin
C10orf105	Other/Unknown	no		DUF5527
COCH	Other/Unknown	no		VWF_A, LCCL, vWFA_dom_sf
COL4A4	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
CRX	Transcription factor	no		HD, Homeodomain-like_sf, Otx_TF_C
ARSG	Phosphatase	yes		Sulfatase_N, Alkaline_phosphatase_core_sf, Sulfatase_CS
SLC9B1	Transporter	yes		Cation/H_exchanger_TM, Na+/solute_symporter_sf, CPA1_transporter
CIB2	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
CCDC40	Other/Unknown	no		CCDC40
PDZD7	Scaffold/PPI	no		PDZ, PDZ_sf, PDZD7_HN-like
FMC1	Other/Unknown	no		FMC1_homologue
DGKQ	Kinase	yes	2.7.1.107	RA_dom, Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom
SIAH2-AS1	Other/Unknown	no
USH2A-AS2	Other/Unknown	no
USH2A-AS1	Other/Unknown	no
GUCA1ANB-GUCA1A	Other/Unknown	no
KIF11	Enzyme (other)	yes	5.6.1.3	Kinesin_motor_dom, Kinesin_motor_CS, Kinesin-assoc_MT-bd_dom
MYO7A	Scaffold/PPI	no		IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom
ATP6V1B1	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_bsu
PDE6A	Transcription factor	no		PDEase_catalytic_dom, GAF, HD/PDEase_dom
SERPINB6	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom
PROM1	Other/Unknown	no		Prominin
BBS1	Other/Unknown	no		Quinoprotein_ADH-like_sf, BBS1, BBS1_N
PRPH2	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS

Expression context

Cohort genes with no expression data: 1.

27 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)	0
broad (>20)	36
unknown	1

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	5
right adrenal gland	4
right adrenal gland cortex	4
left testis	4
right uterine tube	4
mucosa of transverse colon	3
buccal mucosa cell	3
ventricular zone	3
left adrenal gland	3
primordial germ cell in gonad	3
quadriceps femoris	3
right testis	3
rectum	2
adrenal tissue	2
left ovary	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
testis	2
sural nerve	2
blood	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BPNT1	232	ubiquitous	marker	islet of Langerhans, mucosa of transverse colon, rectum
USH1C	203	broad	marker	mucosa of transverse colon, C1 segment of cervical spinal cord, rectum
USH2A	30	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell
CLRN1	61	tissue_specific	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland
CDH23	161	broad	marker	ventricular zone, left ovary, right ovary
CABP4	226	broad	marker	vena cava, cardia of stomach, ventral tegmental area
HDAC6	286	ubiquitous	marker	right hemisphere of cerebellum, adenohypophysis, cerebellar hemisphere
PCDH15	130	tissue_specific	marker	left adrenal gland cortex, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue
USH1G	69	broad	yes	lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis, esophagus squamous epithelium
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
ADGRV1	196	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
CEP250	186	ubiquitous	yes	sural nerve, ventricular zone, cortical plate
OTOP2	37	tissue_specific	marker	mucosa of transverse colon, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
C10orf105	107	tissue_specific	yes	quadriceps femoris, blood, cerebellar vermis
COCH	272	broad	marker	buccal mucosa cell, saphenous vein, skeletal muscle tissue of biceps brachii
COL4A4	187	broad	marker	renal medulla, metanephros cortex, pigmented layer of retina
CRX	54	tissue_specific	marker	pigmented layer of retina, retina, primordial germ cell in gonad
ARSG	135	ubiquitous	marker	blood, stromal cell of endometrium, monocyte
SLC9B1	161	broad	marker	sperm, left testis, right testis
CIB2	272	ubiquitous	marker	right atrium auricular region, cardiac atrium, apex of heart
CCDC40	184	ubiquitous	marker	right uterine tube, bronchial epithelial cell, sural nerve
PDZD7	178	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
FMC1	138	ubiquitous	marker	left testis, right testis, testis
DGKQ	235	ubiquitous	yes	ileal mucosa, pancreatic ductal cell, granulocyte
SIAH2-AS1	161	broad	yes	secondary oocyte, oocyte, buccal mucosa cell
USH2A-AS2	54		yes	quadriceps femoris, anterior cingulate cortex, cerebellar vermis
USH2A-AS1	21		yes	liver, bone marrow, spinal cord
GUCA1ANB-GUCA1A
KIF11	205	ubiquitous	marker	ventricular zone, ganglionic eminence, embryo

Protein interactions among cohort

Intra-cohort edges: 50.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HDAC6	5,961
KIF11	3,788
PROM1	3,302
CEP250	2,707
WHRN	2,499
USH2A	2,332
CIB2	2,249
BBS1	2,189
ATP6V1B1	2,172
CRX	2,076

Intra-cohort edges

A	B	Sources
ADGRV1	CDH23	string_interaction
ADGRV1	CIB2	string_interaction
ADGRV1	CLRN1	string_interaction
ADGRV1	PCDH15	string_interaction
ADGRV1	PDZD7	intact, string_interaction
ADGRV1	USH1G	string_interaction
ADGRV1	USH2A	string_interaction
ADGRV1	WHRN	string_interaction
C10orf105	CDH23	string_interaction
CDH23	CIB2	string_interaction
CDH23	CLRN1	string_interaction
CDH23	COCH	biogrid_interaction, intact
CDH23	OTOA	string_interaction
CDH23	PCDH15	string_interaction
CDH23	PDZD7	string_interaction
CDH23	USH1C	biogrid_interaction, intact
CDH23	USH1G	string_interaction
CDH23	USH2A	string_interaction
CDH23	WHRN	string_interaction
CEP250	CLRN1	string_interaction
CEP250	PDZD7	string_interaction
CEP250	USH1G	string_interaction
CIB2	CLRN1	string_interaction
CIB2	PCDH15	string_interaction
CIB2	PDZD7	intact, string_interaction
CIB2	USH1G	string_interaction
CIB2	USH2A	string_interaction
CIB2	WHRN	string_interaction
CLRN1	PCDH15	string_interaction
CLRN1	PDZD7	string_interaction
CLRN1	USH1G	string_interaction
CLRN1	USH2A	string_interaction
CLRN1	WHRN	string_interaction
COCH	OTOA	string_interaction
CRX	PRPH2	string_interaction
HDAC6	PROM1	biogrid_interaction, intact
MYO7A	USH1C	biogrid_interaction
OTOA	SERPINB6	string_interaction
PCDH15	PDZD7	string_interaction
PCDH15	USH1G	string_interaction
PCDH15	USH2A	string_interaction
PCDH15	WHRN	string_interaction
PDE6A	PRPH2	string_interaction
PDZD7	USH1G	string_interaction
PDZD7	USH2A	intact, string_interaction
PDZD7	WHRN	string_interaction
USH1C	USH1G	biogrid_interaction, intact
USH1G	USH2A	string_interaction
USH1G	WHRN	string_interaction
USH2A	WHRN	string_interaction

Structural data

PDB: 18 · AlphaFold-only: 15 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF11	P52732	62
HDAC6	Q9UBN7	21
USH1C	Q9Y6N9	11
PCDH15	Q96QU1	8
CDH23	Q9H251	6
WHRN	Q9P202	5
USH1G	Q495M9	3
COL4A4	P53420	2
PDZD7	Q9H5P4	2
BPNT1	O95861	1
CEP250	Q9BV73	1
COCH	O43405	1
CRX	O43186	1
CIB2	O75838	1
CCDC40	Q4G0X9	1
MYO7A	Q13402	1
BBS1	Q8NFJ9	1
PRPH2	P23942	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARSG	Q96EG1	91.90
SERPINB6	P35237	91.25
CLRN1	P58418	90.74
PDE6A	P16499	89.80
ATP6V1B1	P15313	87.21
FMC1	Q96HJ9	86.24
PROM1	O43490	85.68
OTOA	Q7RTW8	84.12
DGKQ	P52824	82.56
SLC9B1	Q4ZJI4	79.20
OTOP2	Q7RTS6	78.55
CABP4	P57796	65.01
C10orf105	Q8TEF2	63.46
USH2A	O75445
ADGRV1	Q8WXG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 84. Enrichment computed across 37 evidence-associated genes (22 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 22 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	7	64.9×	6e-10	USH1C, CDH23, PCDH15, USH1G, WHRN, CIB2, MYO7A
Sensory processing of sound by inner hair cells of the cochlea	7	51.9×	2e-09	USH1C, CDH23, PCDH15, USH1G, WHRN, CIB2, MYO7A
Sensory processing of sound	2	28.1×	0.063	CDH23, MYO7A
Cargo trafficking to the periciliary membrane	2	22.6×	0.073	HDAC6, BBS1
Activation of the phototransduction cascade	1	43.3×	0.188	PDE6A
The activation of arylsulfatases	1	39.9×	0.188	ARSG
Dissolution of Fibrin Clot	1	37.1×	0.188	SERPINB6
Anchoring fibril formation	1	34.6×	0.188	COL4A4
Fibronectin matrix formation	1	25.9×	0.188	COL4A4
Crosslinking of collagen fibrils	1	25.9×	0.188	COL4A4
Cytosolic sulfonation of small molecules	1	23.6×	0.188	BPNT1
The canonical retinoid cycle in rods (twilight vision)	1	23.6×	0.188	MYO7A
BBSome-mediated cargo-targeting to cilium	1	22.6×	0.188	BBS1
Chaperone Mediated Autophagy	1	22.6×	0.188	HDAC6
Attachment of bacteria to epithelial cells	1	22.6×	0.188	COL4A4
Effects of PIP2 hydrolysis	1	20.8×	0.188	DGKQ
RUNX2 regulates osteoblast differentiation	1	20.8×	0.188	HDAC6
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1	19.2×	0.188	ARSG
Notch-HLH transcription pathway	1	18.5×	0.188	HDAC6
Laminin interactions	1	17.3×	0.188	COL4A4
HSF1 activation	1	17.3×	0.188	HDAC6
Insulin receptor recycling	1	17.3×	0.188	ATP6V1B1
Transferrin endocytosis and recycling	1	16.7×	0.188	ATP6V1B1
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	16.7×	0.188	ADGRV1
Ion channel transport	2	8.7×	0.188	SLC9B1, ATP6V1B1
Sensory Perception	2	8.7×	0.188	CDH23, MYO7A
ROS and RNS production in phagocytes	1	15.3×	0.188	ATP6V1B1
Late endosomal microautophagy	1	14.8×	0.188	HDAC6
Inactivation, recovery and regulation of the phototransduction cascade	1	14.4×	0.188	PDE6A
Glycosphingolipid metabolism	1	13.7×	0.188	ARSG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 32 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 light stimulus	9	526.6×	2e-23	USH1C, USH2A, CLRN1, CDH23, PCDH15, USH1G, WHRN, ADGRV1 (+1 more)
sensory perception of sound	14	44.1×	2e-18	USH1C, USH2A, CLRN1, CDH23, PCDH15, USH1G, WHRN, OTOA (+6 more)
photoreceptor cell maintenance	10	112.0×	5e-17	USH1C, USH2A, CLRN1, CDH23, PCDH15, USH1G, ADGRV1, CIB2 (+2 more)
equilibrioception	6	451.4×	1e-14	USH1C, CLRN1, CDH23, PCDH15, USH1G, MYO7A
visual perception	10	24.8×	2e-10	USH2A, CLRN1, CDH23, CABP4, ADGRV1, CRX, MYO7A, PDE6A (+2 more)
inner ear receptor cell differentiation	4	421.3×	2e-09	USH2A, WHRN, ADGRV1, PDZD7
auditory receptor cell stereocilium organization	5	131.7×	9e-09	CLRN1, CDH23, WHRN, PDZD7, MYO7A
inner ear receptor cell stereocilium organization	4	105.3×	2e-06	USH1C, USH1G, WHRN, ADGRV1
retina development in camera-type eye	5	39.9×	4e-06	CRX, ARSG, PDE6A, BBS1, PRPH2
establishment of protein localization	4	54.0×	2e-05	USH2A, WHRN, ADGRV1, PDZD7
detection of mechanical stimulus involved in sensory perception of sound	3	87.8×	1e-04	WHRN, ADGRV1, PDZD7
maintenance of animal organ identity	2	210.7×	7e-04	USH2A, ADGRV1
photoreceptor cell morphogenesis	2	175.5×	1e-03	CABP4, BBS1
olfactory behavior	2	117.0×	0.002	ATP6V1B1, BBS1
inner ear morphogenesis	3	28.2×	0.003	USH1C, USH1G, ATP6V1B1
retinal cone cell development	2	87.8×	0.003	USH1C, CABP4
inner ear auditory receptor cell differentiation	2	75.2×	0.004	USH1C, USH2A
establishment of localization in cell	3	15.1×	0.014	USH2A, WHRN, PDZD7
detection of light stimulus involved in visual perception	2	40.5×	0.014	CEP250, PRPH2
response to low light intensity stimulus	1	526.6×	0.019	PRPH2
negative regulation of hydrogen peroxide metabolic process	1	526.6×	0.019	HDAC6
cellular response to topologically incorrect protein	1	526.6×	0.019	HDAC6
pigment granule transport	1	526.6×	0.019	MYO7A
polyubiquitinated misfolded protein transport	1	526.6×	0.019	HDAC6
adult behavior	2	29.3×	0.020	ATP6V1B1, BBS1
cochlea development	2	29.3×	0.020	CDH23, MYO7A
calcium ion homeostasis	2	27.7×	0.021	CIB2, ATP6V1B1
actin filament organization	3	11.1×	0.021	CLRN1, HDAC6, MYO7A
protein localization to cilium	2	25.1×	0.024	CCDC40, BBS1
cerebellar Purkinje cell layer formation	1	263.3×	0.024	WHRN

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 34

Druggability breadth: 9 of 37 evidence-associated genes (24%) 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
HDAC6	EVANS BLUE FREE ACID
PDE6A	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HDAC6	94	4
PDE6A	8	4
KIF11	6	3
BPNT1	0	0
USH1C	0	0
USH2A	0	0
CLRN1	0	0
CDH23	0	0
CABP4	0	0
PCDH15	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EVANS BLUE FREE ACID	4	HDAC6
FEBUXOSTAT	4	HDAC6
CELECOXIB	4	HDAC6
PHENYL AMINOSALICYLATE	4	HDAC6
TRIFLUPROMAZINE HYDROCHLORIDE	4	HDAC6
GIVINOSTAT	4	HDAC6
AXITINIB	4	HDAC6
MONOBENZONE	4	HDAC6
NITAZOXANIDE	4	HDAC6
ATORVASTATIN	4	HDAC6
PIPERACETAZINE	4	HDAC6
INDOPROFEN	4	HDAC6
DAUNORUBICIN	4	HDAC6
RUXOLITINIB	4	HDAC6
ABAMETAPIR	4	HDAC6
ATALUREN	4	HDAC6
BORTEZOMIB	4	HDAC6
ROMIDEPSIN	4	HDAC6
BELINOSTAT	4	HDAC6
PANOBINOSTAT	4	HDAC6
BENDAMUSTINE	4	HDAC6
LOVASTATIN	4	HDAC6
MARIBAVIR	4	HDAC6
THIABENDAZOLE	4	HDAC6
GENTIAN VIOLET	4	HDAC6
FLUPHENAZINE	4	HDAC6
BUFEXAMAC	4	HDAC6
VORINOSTAT	4	HDAC6
PHENYLBUTANOIC ACID	4	HDAC6
SODIUM PHENYLBUTYRATE	4	HDAC6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HDAC6	3,537	Binding:3494, ADMET:35, Functional:5, Toxicity:3
KIF11	193	Binding:185, Functional:8
PDE6A	69	Binding:65, ADMET:3, Functional:1
PCDH15	9	Binding:9
ARSG	2	Binding:2
BPNT1	1	Binding:1
ATP6V1B1	1	Binding:1
SERPINB6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BPNT1	3.1.3.7	3’(2’),5’-bisphosphate nucleotidase
HDAC6	3.5.1.98	histone deacetylase
DGKQ	2.7.1.107	diacylglycerol kinase (ATP)
KIF11	5.6.1.3	plus-end-directed kinesin ATPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
HDAC6	3,537
KIF11	193

Pharmacogenomics

Cohort genes with a PharmGKB record: 33; 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)
EVANS BLUE FREE ACID	4	HDAC6
FEBUXOSTAT	4	HDAC6
CELECOXIB	4	HDAC6
PHENYL AMINOSALICYLATE	4	HDAC6
TRIFLUPROMAZINE HYDROCHLORIDE	4	HDAC6
GIVINOSTAT	4	HDAC6
AXITINIB	4	HDAC6
MONOBENZONE	4	HDAC6
NITAZOXANIDE	4	HDAC6
ATORVASTATIN	4	HDAC6
PIPERACETAZINE	4	HDAC6
INDOPROFEN	4	HDAC6
DAUNORUBICIN	4	HDAC6
RUXOLITINIB	4	HDAC6
ABAMETAPIR	4	HDAC6
ATALUREN	4	HDAC6
BORTEZOMIB	4	HDAC6
ROMIDEPSIN	4	HDAC6
BELINOSTAT	4	HDAC6
PANOBINOSTAT	4	HDAC6
BENDAMUSTINE	4	HDAC6
LOVASTATIN	4	HDAC6
MARIBAVIR	4	HDAC6
THIABENDAZOLE	4	HDAC6
GENTIAN VIOLET	4	HDAC6
FLUPHENAZINE	4	HDAC6
BUFEXAMAC	4	HDAC6
VORINOSTAT	4	HDAC6
PHENYLBUTANOIC ACID	4	HDAC6
SODIUM PHENYLBUTYRATE	4	HDAC6

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	HDAC6, PDE6A
B	Phased (≥1) drug, not yet approved	1	KIF11
C	Druggable family + PDB, no drug	1	BPNT1
D	Druggable family + AlphaFold only, no drug	5	USH2A, ADGRV1, ARSG, SLC9B1, DGKQ
E	Difficult family or no structure, no drug	28	USH1C, CLRN1, CDH23, CABP4, PCDH15, USH1G, WHRN, OTOA, CEP250, OTOP2 (+18 more)

Undrugged target profiles

34 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BPNT1	1	—
USH1C	0	—
USH2A	0	—
CLRN1	0	—
CDH23	0	—
CABP4	0	—
PCDH15	9	—
USH1G	0	—
WHRN	0	—
OTOA	0	—
ADGRV1	0	—
CEP250	0	—
OTOP2	0	—
C10orf105	0	—
COCH	0	—
COL4A4	0	—
CRX	0	—
ARSG	2	—
SLC9B1	0	—
CIB2	0	—
CCDC40	0	—
PDZD7	0	—
FMC1	0	—
DGKQ	0	—
SIAH2-AS1	0	—
USH2A-AS2	0	—
USH2A-AS1	0	—
GUCA1ANB-GUCA1A	0	—
MYO7A	0	—
ATP6V1B1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 18.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	13
PHASE1/PHASE2	3
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT02065011	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Determine the Long-Term Safety, Tolerability and Biological Activity of SAR421869 in Patients With Usher Syndrome Type 1B
NCT04355689	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of NPI-001 Tablets for RP Associated With Usher Syndrome
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT01505062	PHASE1/PHASE2	TERMINATED	Study of SAR421869 in Participants With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT04665726	Not specified	RECRUITING	Natural History Study of Usher Syndrome ( Light4Deaf )
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT07278843	Not specified	RECRUITING	Natural History of Photoreceptor Degeneration in USH1B: Clinical Parameters and Validation of Functional Vision Tests in MYO7A
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance
NCT00004345	Not specified	TERMINATED	Study of Dietary N-3 Fatty Acids in Patients With Retinitis Pigmentosa and Usher Syndrome
NCT00016471	Not specified	COMPLETED	A Genetic Analysis of Usher Syndrome in Ashkenazi Jews
NCT00106743	Not specified	COMPLETED	Natural History and Genetic Studies of Usher Syndrome
NCT01954953	Not specified	UNKNOWN	Clinical and Genetic Examination of Usher Syndrome Patients’ Cohort in Europe
NCT03319524	Not specified	COMPLETED	Clinical and Genetic Testing of Patients With Usher Syndrome
NCT03901391	Not specified	COMPLETED	Prospective Open Clinical and Genetic Study of Patients With Retinitis Pigmentosa
NCT03990727	Not specified	UNKNOWN	Phenotype Correlates Genotype of Inherited Retina Dystrophies, Retinitis Pigmentosa, Con>Rod Dystrophies.
NCT04906135	Not specified	COMPLETED	Auditory Neural Function in Implanted Patients With Usher Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CHEMBL5435500	0	1