Joubert syndrome

Summary

Joubert syndrome (MONDO:0018772) is a disease (an umbrella term covering 39 Mondo subtypes) caused by ARL13B (GenCC Definitive), with 65 cohort genes and 3 clinical trials. The dominant Reactome pathway is Anchoring of the basal body to the plasma membrane (14 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: ARL13B (GenCC Definitive)
• Umbrella term: 39 Mondo subtypes
• Cohort genes: 65
• ClinVar variants: 12,999
• Phenotypes (HPO): 37
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.6666	Worldwide	Validated
Point prevalence	1-9 / 1 000 000	0.47	Italy	Validated
Prevalence at birth	1-9 / 100 000	5	Spain	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000657	Oculomotor apraxia	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001320	Cerebellar vermis hypoplasia	Very frequent (80-99%)
HP:0002104	Apnea	Very frequent (80-99%)
HP:0002793	Abnormal pattern of respiration	Very frequent (80-99%)
HP:0002876	Episodic tachypnea	Very frequent (80-99%)
HP:0000276	Long face	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0004422	Biparietal narrowing	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000426	Prominent nasal bridge	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0000864	Abnormality of the hypothalamus-pituitary axis	Occasional (5-29%)
HP:0001161	Hand polydactyly	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001696	Situs inversus totalis	Occasional (5-29%)
HP:0001829	Foot polydactyly	Occasional (5-29%)
HP:0002084	Encephalocele	Occasional (5-29%)
HP:0002126	Polymicrogyria	Occasional (5-29%)
HP:0002251	Aganglionic megacolon	Occasional (5-29%)
HP:0002269	Abnormality of neuronal migration	Occasional (5-29%)
HP:0002553	Highly arched eyebrow	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0003312	Abnormal form of the vertebral bodies	Occasional (5-29%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome
Mondo ID	MONDO:0018772
OMIM	213300
Orphanet	475
DOID	DOID:0050777
ICD-11	1414756318
NCIT	C74996
SNOMED CT	716997004
UMLS	C5979921
MedGen	1876534
GARD	0006802
NORD	1312
Is cancer (heuristic)	no

Also known as: cerebellar vermis agenesis · cerebelloparenchymal disorder IV · classic Joubert syndrome · CPD IV · Joubert syndrome · Joubert syndrome type A · Joubert-Boltshauser syndrome · pure Joubert syndrome

Data availability: 12,999 ClinVar variants · 26 GenCC gene-disease records · 8 cell lines.

Disease family

An umbrella term covering 39 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert 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, 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, Usher 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 (39): Joubert syndrome 1, Joubert syndrome 10, Joubert syndrome 2, Joubert syndrome 3, Joubert syndrome with renal defect, Joubert syndrome 5, Joubert syndrome 6, Joubert syndrome 7, Joubert syndrome 9, Joubert syndrome 8, Joubert syndrome 13, Joubert syndrome 14, Joubert syndrome 15, Joubert syndrome 16, Joubert syndrome 17, Joubert syndrome 18, Joubert syndrome 20, Joubert syndrome 21, Joubert syndrome 22, Joubert syndrome 23, Joubert syndrome 24, Joubert syndrome 25, Joubert syndrome 26, Joubert syndrome 27, Joubert syndrome 28, Joubert syndrome 38, Joubert syndrome 39, Joubert syndrome 40, Joubert syndrome 37, Joubert syndrome 35, Joubert syndrome 36, Joubert syndrome 30, Joubert syndrome 32, Joubert syndrome 31, Joubert syndrome 33, Joubert syndrome 19, Joubert syndrome 29, Joubert syndrome 11, Joubert syndrome 34

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

600 retrieved; paginated sample, class counts are floors:

354 uncertain significance, 82 pathogenic, 65 likely benign, 47 pathogenic/likely pathogenic, 25 likely pathogenic, 23 conflicting classifications of pathogenicity, 3 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1011633	NC_000006.11:g.(?135769428)(135769613_?)del	AHI1	Pathogenic	criteria provided, single submitter
1065721	NM_001134831.2(AHI1):c.3235C>T (p.Arg1079Ter)	AHI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068435	NM_001134831.2(AHI1):c.2623+2T>A	AHI1	Pathogenic	criteria provided, single submitter
1070164	NM_001134831.2(AHI1):c.1583C>A (p.Ser528Ter)	AHI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070615	NC_000006.11:g.(?135749761)(135784450_?)del	AHI1	Pathogenic	criteria provided, single submitter
1072698	NC_000006.11:g.(?135751000)(135754414_?)del	AHI1	Pathogenic	criteria provided, single submitter
1073454	NM_001134831.2(AHI1):c.1166C>G (p.Ser389Ter)	AHI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074384	NM_001134831.2(AHI1):c.1900dup (p.Tyr634fs)	AHI1	Pathogenic	criteria provided, single submitter
1074597	NM_001134831.2(AHI1):c.2495del (p.Ile831_Leu832insTer)	AHI1	Pathogenic	criteria provided, single submitter
1075243	NM_001134831.2(AHI1):c.1983del (p.Trp662fs)	AHI1	Pathogenic	criteria provided, multiple submitters, no conflicts
1068683	NM_001378615.1(CC2D2A):c.4086del (p.Asp1364fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1069485	NM_001378615.1(CC2D2A):c.3376G>A (p.Glu1126Lys)	CC2D2A	Pathogenic	criteria provided, single submitter
1070038	NM_001378615.1(CC2D2A):c.1297del (p.Gln433fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1071905	NM_001378615.1(CC2D2A):c.4256del (p.Gly1419fs)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1073574	NM_001378615.1(CC2D2A):c.2898_2899dup (p.Ile967fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1074596	NM_001378615.1(CC2D2A):c.1538G>A (p.Trp513Ter)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1074828	NM_001378615.1(CC2D2A):c.2875del (p.Glu959fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1075055	NM_001378615.1(CC2D2A):c.418_419insGAGGGAGGAGCCAAGATGGCCGAATAGGAACAGCTCCGGTCTACAGCTCCCAGCGTGAGCGACGCAGAAGACGGTGATTTCTGCATCTCCATCTGAGGTACCGGGTTCATNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAAAGAATTGG (p.Glu140delinsGlyGlyArgSerGlnAspGlyArgIleGlyThrAlaProValTyrSerSerGlnArgGluArgArgArgArgArgTer)	CC2D2A	Pathogenic	criteria provided, single submitter
1076226	NC_000004.11:g.(?15480341)(15482457_?)del	CC2D2A	Pathogenic	criteria provided, single submitter
1076327	NM_001378615.1(CC2D2A):c.3320_3321del (p.Phe1107fs)	CC2D2A	Pathogenic	criteria provided, single submitter
1032903	NM_025114.4(CEP290):c.2632del (p.Ile878fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1032904	NM_025114.4(CEP290):c.3934A>T (p.Arg1312Ter)	CEP290	Pathogenic	criteria provided, single submitter
1068566	NM_025114.4(CEP290):c.5783del (p.Lys1928fs)	CEP290	Pathogenic	criteria provided, single submitter
1068669	NM_025114.4(CEP290):c.5348_5351del (p.His1783fs)	CEP290	Pathogenic	criteria provided, single submitter
1068974	NM_025114.4(CEP290):c.1400del (p.Asn467fs)	CEP290	Pathogenic	criteria provided, single submitter
1069520	NM_025114.4(CEP290):c.3488_3494dup (p.Val1166fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069579	NM_025114.4(CEP290):c.5235_5238del (p.Ser1745fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069582	NM_025114.4(CEP290):c.4090G>T (p.Glu1364Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1069639	NM_025114.4(CEP290):c.1668del (p.Arg557fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069905	NM_025114.4(CEP290):c.843_845del (p.Tyr281_Gln282delinsTer)	CEP290	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 185 · Orphanet: 124 · 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
AHI1	Definitive	Autosomal recessive	Joubert syndrome 3	10
ARL13B	Definitive	Autosomal recessive	Joubert syndrome	6
ARMC9	Definitive	Autosomal recessive	Joubert syndrome 30	5
CEP104	Definitive	Autosomal recessive	Joubert syndrome 25	4
CEP41	Definitive	Autosomal recessive	Joubert syndrome 15	4
CPLANE1	Definitive	Autosomal recessive	Joubert syndrome 17	8
CSPP1	Definitive	Autosomal recessive	Joubert syndrome 21	6
INPP5E	Definitive	Autosomal recessive	Joubert syndrome 1	14
KIAA0586	Definitive	Autosomal recessive	Joubert syndrome 23	10
PIBF1	Definitive	Autosomal recessive	Joubert syndrome 33	4
PMPCA	Definitive	Autosomal recessive	Joubert syndrome 1	18
TMEM237	Definitive	Autosomal recessive	Joubert syndrome 14	9
ARL3	Strong	Autosomal recessive	Joubert syndrome 35	10
B9D1	Strong	Autosomal recessive	Joubert syndrome 27	6
CEP120	Strong	Autosomal recessive	Joubert syndrome 31	6
KATNIP	Strong	Autosomal recessive	Joubert syndrome 26	3
MKS1	Strong	Autosomal recessive	Joubert syndrome 28	11
SUFU	Strong	Autosomal recessive	Joubert syndrome 32	16
TCTN1	Strong	Autosomal recessive	Joubert syndrome 13	5
TCTN2	Strong	Autosomal recessive	Joubert syndrome 24	7
TMEM67	Strong	Autosomal recessive	Joubert syndrome 6	13
SLC30A7	Moderate	Autosomal dominant	Joubert syndrome	2
CBY1	Supportive	Autosomal recessive	Joubert syndrome	2
HYLS1	Supportive	Autosomal recessive	Joubert syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP41	Orphanet:220493	Joubert syndrome with ocular defect
CEP41	Orphanet:475	Isolated Joubert syndrome
CBY1	Orphanet:475	Isolated Joubert syndrome
TMEM237	Orphanet:220497	Joubert syndrome with renal defect
TMEM237	Orphanet:2318	Joubert syndrome with oculorenal defect
TMEM237	Orphanet:475	Isolated Joubert syndrome
TMEM237	Orphanet:564	Meckel syndrome
PMPCA	Orphanet:1170	Autosomal recessive cerebelloparenchymal disorder type 3
KIAA0586	Orphanet:397715	Joubert syndrome with Jeune asphyxiating thoracic dystrophy
KIAA0586	Orphanet:475	Isolated Joubert syndrome
ARMC9	Orphanet:475	Isolated Joubert syndrome
INPP5E	Orphanet:1454	Joubert syndrome with hepatic defect
INPP5E	Orphanet:220493	Joubert syndrome with ocular defect
INPP5E	Orphanet:475	Isolated Joubert syndrome
INPP5E	Orphanet:75858	MORM syndrome
AHI1	Orphanet:220493	Joubert syndrome with ocular defect
AHI1	Orphanet:475	Isolated Joubert syndrome
AHI1	Orphanet:791	Retinitis pigmentosa
PIBF1	Orphanet:475	Isolated Joubert syndrome
B9D1	Orphanet:475	Isolated Joubert syndrome
B9D1	Orphanet:564	Meckel syndrome
CEP104	Orphanet:475	Isolated Joubert syndrome
CEP104	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
ARL13B	Orphanet:475	Isolated Joubert syndrome
TCTN2	Orphanet:475	Isolated Joubert syndrome
TCTN2	Orphanet:564	Meckel syndrome
CPLANE1	Orphanet:2754	Orofaciodigital syndrome type 6
CPLANE1	Orphanet:475	Isolated Joubert syndrome
CPLANE1	Orphanet:65684	Monomelic amyotrophy
TCTN1	Orphanet:475	Isolated Joubert syndrome
TCTN1	Orphanet:564	Meckel syndrome
CSPP1	Orphanet:397715	Joubert syndrome with Jeune asphyxiating thoracic dystrophy
CSPP1	Orphanet:475	Isolated Joubert syndrome
CSPP1	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
KATNIP	Orphanet:475	Isolated Joubert syndrome
MKS1	Orphanet:110	Bardet-Biedl syndrome
MKS1	Orphanet:220493	Joubert syndrome with ocular defect
MKS1	Orphanet:475	Isolated Joubert syndrome
MKS1	Orphanet:564	Meckel syndrome
SUFU	Orphanet:2495	Meningioma
SUFU	Orphanet:251858	Medulloblastoma with extensive nodularity
SUFU	Orphanet:251863	Desmoplastic/nodular medulloblastoma
SUFU	Orphanet:263662	Familial multiple meningioma
SUFU	Orphanet:280200	Microform holoprosencephaly
SUFU	Orphanet:377	Gorlin syndrome

Cohort genes → proteins

65 cohort genes, 64 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	65

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CEP41	HGNC:12370	ENSG00000106477	Q9BYV8	Centrosomal protein of 41 kDa	gencc,clinvar
CBY1	HGNC:1307	ENSG00000100211	Q9Y3M2	Protein chibby homolog 1	gencc,clinvar
TMEM237	HGNC:14432	ENSG00000155755	Q96Q45	Transmembrane protein 237	gencc,clinvar
PMPCA	HGNC:18667	ENSG00000165688	Q10713	Mitochondrial-processing peptidase subunit alpha	gencc,clinvar
KIAA0586	HGNC:19960	ENSG00000100578	Q9BVV6	Protein TALPID3	gencc,clinvar
ARMC9	HGNC:20730	ENSG00000135931	Q7Z3E5	LisH domain-containing protein ARMC9	gencc,clinvar
INPP5E	HGNC:21474	ENSG00000148384	Q9NRR6	Phosphatidylinositol polyphosphate 5-phosphatase type IV	gencc,clinvar
AHI1	HGNC:21575	ENSG00000135541	Q8N157	Jouberin	gencc,clinvar
PIBF1	HGNC:23352	ENSG00000083535	Q8WXW3	Progesterone-induced-blocking factor 1	gencc,clinvar
B9D1	HGNC:24123	ENSG00000108641	Q9UPM9	B9 domain-containing protein 1	gencc,clinvar
CEP104	HGNC:24866	ENSG00000116198	O60308	Centrosomal protein of 104 kDa	gencc,clinvar
ARL13B	HGNC:25419	ENSG00000169379	Q3SXY8	ADP-ribosylation factor-like protein 13B	gencc,clinvar
TCTN2	HGNC:25774	ENSG00000168778	Q96GX1	Tectonic-2	gencc,clinvar
CPLANE1	HGNC:25801	ENSG00000197603	Q9H799	Ciliogenesis and planar polarity effector 1	gencc,clinvar
TCTN1	HGNC:26113	ENSG00000204852	Q2MV58	Tectonic-1	gencc,clinvar
CSPP1	HGNC:26193	ENSG00000104218	Q1MSJ5	Centrosome and spindle pole-associated protein 1	gencc,clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	gencc,clinvar
KATNIP	HGNC:29068	ENSG00000047578	O60303	Katanin-interacting protein	gencc,clinvar
MKS1	HGNC:7121	ENSG00000011143	Q9NXB0	Tectonic-like complex member MKS1	gencc,clinvar
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	gencc
SLC30A7	HGNC:19306	ENSG00000162695	Q8NEW0	Zinc transporter 7	gencc
HYLS1	HGNC:26558	ENSG00000198331	Q96M11	Centriolar and ciliogenesis-associated protein HYLS1	gencc
CEP120	HGNC:26690	ENSG00000168944	Q8N960	Centrosomal protein of 120 kDa	gencc
ARL3	HGNC:694	ENSG00000138175	P36405	ADP-ribosylation factor-like protein 3	gencc
BST1	HGNC:1118	ENSG00000109743	Q10588	ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2	clinvar
USH2A	HGNC:12601	ENSG00000042781	O75445	Usherin	clinvar
RLIM	HGNC:13429	ENSG00000131263	Q9NVW2	E3 ubiquitin-protein ligase RLIM	clinvar
CARD9	HGNC:16391	ENSG00000187796	Q9H257	Caspase recruitment domain-containing protein 9	clinvar
RCOR1	HGNC:17441	ENSG00000089902	Q9UKL0	REST corepressor 1	clinvar
ATP6V0A2	HGNC:18481	ENSG00000185344	Q9Y487	V-type proton ATPase 116 kDa subunit a 2	clinvar
IFT38	HGNC:19009	ENSG00000103351	Q96AJ1	Clusterin-associated protein 1	clinvar
TOGARAM1	HGNC:19959	ENSG00000198718	Q9Y4F4	TOG array regulator of axonemal microtubules protein 1	clinvar
EGFL7	HGNC:20594	ENSG00000172889	Q9UHF1	Epidermal growth factor-like protein 7	clinvar
CHD7	HGNC:20626	ENSG00000171316	Q9P2D1	ATP-dependent chromatin remodeler CHD7	clinvar
GDPD1	HGNC:20883	ENSG00000153982	Q8N9F7	Lysophospholipase D GDPD1	clinvar
IFT74	HGNC:21424	ENSG00000096872	Q96LB3	Intraflagellar transport protein 74 homolog	clinvar
PLPP6	HGNC:23682	ENSG00000205808	Q8IY26	Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6	clinvar
ATXN3L	HGNC:24173	ENSG00000123594	Q9H3M9	Ataxin-3-like protein	clinvar
C2CD3	HGNC:24564	ENSG00000168014	Q4AC94	C2 domain-containing protein 3	clinvar
EXOC8	HGNC:24659	ENSG00000116903	Q8IYI6	Exocyst complex component 8	clinvar
FTO	HGNC:24678	ENSG00000140718	Q9C0B1	Alpha-ketoglutarate-dependent dioxygenase FTO	clinvar
TMEM216	HGNC:25018	ENSG00000187049	Q9P0N5	Transmembrane protein 216	clinvar
RLIG1	HGNC:25322	ENSG00000133641	Q8N999	RNA ligase 1	clinvar
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	clinvar
PGAP1	HGNC:25712	ENSG00000197121	Q75T13	GPI inositol-deacylase	clinvar
TMEM17	HGNC:26623	ENSG00000186889	Q86X19	Transmembrane protein 17	clinvar
TMEM218	HGNC:27344	ENSG00000150433	A2RU14	Transmembrane protein 218	clinvar
WDPCP	HGNC:28027	ENSG00000143951	O95876	WD repeat-containing and planar cell polarity effector protein fritz homolog	clinvar
LRRC34	HGNC:28408	ENSG00000171757	Q8IZ02	Leucine-rich repeat-containing protein 34	clinvar
B9D2	HGNC:28636	ENSG00000123810	Q9BPU9	B9 domain-containing protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP41	Centrosomal protein of 41 kDa	Required during ciliogenesis for tubulin glutamylation in cilium.
CBY1	Protein chibby homolog 1	Inhibits the Wnt/Wingless pathway by binding to CTNNB1/beta-catenin and inhibiting beta-catenin-mediated transcriptional activation through competition with TCF/LEF transcription factors.
TMEM237	Transmembrane protein 237	Component of the transition zone in primary cilia.
PMPCA	Mitochondrial-processing peptidase subunit alpha	Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins.
KIAA0586	Protein TALPID3	Required for ciliogenesis and sonic hedgehog/SHH signaling.
ARMC9	LisH domain-containing protein ARMC9	Involved in ciliogenesis.
INPP5E	Phosphatidylinositol polyphosphate 5-phosphatase type IV	Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,5-bispho…
AHI1	Jouberin	Involved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium.
PIBF1	Progesterone-induced-blocking factor 1	Plays a role in ciliogenesis.
B9D1	B9 domain-containing protein 1	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
CEP104	Centrosomal protein of 104 kDa	Required for ciliogenesis and for structural integrity at the ciliary tip.
ARL13B	ADP-ribosylation factor-like protein 13B	Cilium-specific protein required to control the microtubule-based, ciliary axoneme structure.
TCTN2	Tectonic-2	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
CPLANE1	Ciliogenesis and planar polarity effector 1	Involved in ciliogenesis.
TCTN1	Tectonic-1	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
CSPP1	Centrosome and spindle pole-associated protein 1	May play a role in cell-cycle-dependent microtubule organization.
TMEM67	Meckelin	Required for ciliary structure and function.
KATNIP	Katanin-interacting protein	May influence the stability of microtubules (MT), possibly through interaction with the MT-severing katanin complex.
MKS1	Tectonic-like complex member MKS1	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.
SLC30A7	Zinc transporter 7	Zinc ion transporter mediating zinc entry from the cytosol into the lumen of organelles along the secretory pathway.
HYLS1	Centriolar and ciliogenesis-associated protein HYLS1	Plays a role in ciliogenesis.
CEP120	Centrosomal protein of 120 kDa	Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome.
ARL3	ADP-ribosylation factor-like protein 3	Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP).
BST1	ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2	Catalyzes both the synthesis of cyclic ADP-beta-D-ribose (cADPR) from NAD(+), and its hydrolysis to ADP-D-ribose (ADPR).
USH2A	Usherin	Involved in hearing and vision as member of the USH2 complex.
RLIM	E3 ubiquitin-protein ligase RLIM	E3 ubiquitin-protein ligase that acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/…
CARD9	Caspase recruitment domain-containing protein 9	Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors.
RCOR1	REST corepressor 1	Essential component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells.
ATP6V0A2	V-type proton ATPase 116 kDa subunit a 2	Subunit of the V0 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.
IFT38	Clusterin-associated protein 1	Required for cilia biogenesis.
TOGARAM1	TOG array regulator of axonemal microtubules protein 1	Involved in ciliogenesis.
EGFL7	Epidermal growth factor-like protein 7	Regulates vascular tubulogenesis in vivo.
CHD7	ATP-dependent chromatin remodeler CHD7	ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
GDPD1	Lysophospholipase D GDPD1	Hydrolyzes lysoglycerophospholipids to produce lysophosphatidic acid (LPA) and the corresponding amines.
IFT74	Intraflagellar transport protein 74 homolog	Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium.
PLPP6	Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6	Magnesium-independent polyisoprenoid diphosphatase that catalyzes the sequential dephosphorylation of presqualene, farnesyl, geranyl and geranylgeranyl diphosphates.
ATXN3L	Ataxin-3-like protein	Deubiquitinating enzyme that cleaves both ‘Lys-48’-linked and ‘Lys-63’-linked poly-ubiquitin chains (in vitro).
C2CD3	C2 domain-containing protein 3	Component of the centrioles that acts as a positive regulator of centriole elongation.
EXOC8	Exocyst complex component 8	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
FTO	Alpha-ketoglutarate-dependent dioxygenase FTO	RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis.
TMEM216	Transmembrane protein 216	Essential for primary ciliogenesis and embryonic development, facilitating the activation of Hedgehog (Hh) signaling pathway.
RLIG1	RNA ligase 1	Functions as an RNA ligase, in vitro.
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.
PGAP1	GPI inositol-deacylase	GPI inositol-deacylase that catalyzes the remove of the acyl chain linked to the 2-OH position of inositol ring from the GPI-anchored protein (GPI-AP) in the endoplasmic reticulum.
TMEM17	Transmembrane protein 17	Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
TMEM218	Transmembrane protein 218	May be involved in ciliary biogenesis or function.
WDPCP	WD repeat-containing and planar cell polarity effector protein fritz homolog	Probable effector of the planar cell polarity signaling pathway which regulates the septin cytoskeleton in both ciliogenesis and collective cell movements.
LRRC34	Leucine-rich repeat-containing protein 34	Highly expressed in stem cells where it may be involved in regulation of pluripotency.
B9D2	B9 domain-containing protein 2	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.

Protein-family classification

Druggable: 10 · Difficult: 8 · Unknown: 47 · Druggable fraction: 0.15

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
Other/Unknown	47	1.3×	0.037
Scaffold/PPI	5	1.3×	0.854
Phosphatase	1	1.3×	0.854
Transporter	1	1.2×	0.854
Protease	2	1.1×	0.854
Enzyme (other)	5	0.9×	0.854
Antibody/Immunoglobulin	1	0.5×	0.989
Transcription factor	3	0.4×	0.989

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP41	Other/Unknown	no		Rhodanese-like_dom, Rhodanese-like_dom_sf, CEP41
CBY1	Other/Unknown	no		Chibby_fam
TMEM237	Other/Unknown	no		TMEM237
PMPCA	Protease	yes	3.4.24.64	Pept_M16_Zn_BS, Peptidase_M16_C, Metalloenz_LuxS/M16
KIAA0586	Other/Unknown	no		TALPID3
ARMC9	Other/Unknown	no		LisH, ARM-like, ARM-type_fold
INPP5E	Enzyme (other)	yes	3.1.3.36	IPPc, Endo/exonu/phosph_ase_sf, INPP5E
AHI1	Scaffold/PPI	no		SH3_domain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
PIBF1	Other/Unknown	no		PIBF1
B9D1	Other/Unknown	no		C2_B9-type_dom
CEP104	Transcription factor	no		Galactose-bd-like_sf, ARM-like, ARM-type_fold
ARL13B	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, P-loop_NTPase
TCTN2	Other/Unknown	no		TCTN1-3_dom, TCTN1-3, TCTN1-3_N
CPLANE1	Scaffold/PPI	no		CPLANE1, WD40_repeat_dom_sf
TCTN1	Other/Unknown	no		TCTN1-3_dom, TCTN1-3, TCTN1-3_N
CSPP1	Other/Unknown	no		CSPP1, CSPP1_C
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
KATNIP	Other/Unknown	no		KATNIP, KATNIP_dom
MKS1	Other/Unknown	no		C2_B9-type_dom
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain
SLC30A7	Other/Unknown	no		Cation_efflux, Cation_efflux_TMD_sf, Msc2-like
HYLS1	Other/Unknown	no		HYLS1, HYLS1_C_dom, Centriolar_ciliogenesis_assoc
CEP120	Other/Unknown	no		C2_dom, DUF3668, C2_domain_sf
ARL3	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, P-loop_NTPase
BST1	Other/Unknown	no		ADP-ribosyl_cyclase
USH2A	Antibody/Immunoglobulin	yes		Laminin_G, LE_dom, FN3_dom
RLIM	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, RING_finger_E3_ligase
CARD9	Other/Unknown	no		CARD, DEATH-like_dom_sf, CARD_CARD9
RCOR1	Transcription factor	no		ELM2_dom, SANT/Myb, Homeodomain-like_sf
ATP6V0A2	Enzyme (other)	yes	7.1.2.1	V-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka
IFT38	Other/Unknown	no		Clusterin-associated_protein-1
TOGARAM1	Other/Unknown	no		ARM-like, ARM-type_fold, TOG
EGFL7	Other/Unknown	no		EGF, EGF-like_Ca-bd_dom, Growth_fac_rcpt_cys_sf
CHD7	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
GDPD1	Enzyme (other)	yes	3.1.4.46	PLC-like_Pdiesterase_TIM-brl, GP_PDE_dom, GDPD-Related
IFT74	Other/Unknown	no		IFT74
PLPP6	Other/Unknown	no		PAP2/HPO, PAP2/HPO_sf
ATXN3L	Other/Unknown	no		UIM_dom, Josephin, Ataxin-3
C2CD3	Other/Unknown	no		C2_dom, C2_domain_sf, C2_C2CD3
EXOC8	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, Cullin_repeat-like_dom_sf
FTO	Enzyme (other)	yes	1.14.11.53	FTO_C, FTO_cat_dom, FTO
TMEM216	Other/Unknown	no		Uncharacterised_TM-17
RLIG1	Other/Unknown	no		RLIG1
OFD1	Other/Unknown	no		LisH, OFD1
PGAP1	Other/Unknown	no		PGAP1-ab_dom-like, AB_hydrolase_fold, PGAP1/BST1
TMEM17	Other/Unknown	no		Uncharacterised_TM-17
TMEM218	Other/Unknown	no		Tmem218, TMEM218_N
WDPCP	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, Frtz, WD40_repeat_dom_sf
LRRC34	Other/Unknown	no		Leu-rich_rpt, LRR_dom_sf, LRR-containing_regulator
B9D2	Other/Unknown	no		C2_B9-type_dom

Expression context

Cohort genes with no expression data: 0.

55 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)	1
broad (>20)	64
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	16
bronchial epithelial cell	16
secondary oocyte	11
calcaneal tendon	10
oocyte	8
sperm	7
male germ line stem cell (sensu Vertebrata) in testis	7
buccal mucosa cell	7
ventricular zone	5
sural nerve	5
epithelium of bronchus	5
left testis	4
adenohypophysis	4
monocyte	4
endothelial cell	4
primordial germ cell in gonad	4
adrenal tissue	3
pituitary gland	3
olfactory segment of nasal mucosa	3
kidney epithelium	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP41	237	ubiquitous	marker	sperm, left testis, right testis
CBY1	277	ubiquitous	marker	oocyte, secondary oocyte, right uterine tube
TMEM237	250	ubiquitous	marker	calcaneal tendon, adrenal tissue, ventricular zone
PMPCA	276	ubiquitous	marker	right lobe of liver, adrenal tissue, apex of heart
KIAA0586	247	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
ARMC9	244	ubiquitous	marker	stromal cell of endometrium, secondary oocyte, oocyte
INPP5E	279	ubiquitous	yes	right uterine tube, secondary oocyte, oocyte
AHI1	276	ubiquitous	marker	pituitary gland, calcaneal tendon, right hemisphere of cerebellum
PIBF1	273	ubiquitous	marker	calcaneal tendon, ventricular zone, sural nerve
B9D1	224	ubiquitous	marker	right uterine tube, adenohypophysis, left testis
CEP104	284	ubiquitous	marker	secondary oocyte, buccal mucosa cell, sperm
ARL13B	237	ubiquitous	marker	secondary oocyte, calcaneal tendon, bronchial epithelial cell
TCTN2	218	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, olfactory bulb
CPLANE1	195	ubiquitous	marker	sural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
TCTN1	230	ubiquitous	marker	right uterine tube, adenohypophysis, olfactory segment of nasal mucosa
CSPP1	275	ubiquitous	marker	bronchial epithelial cell, sperm, right uterine tube
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
KATNIP	251	ubiquitous	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
MKS1	182	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, left ovary
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava
SLC30A7	249	ubiquitous	marker	oviduct epithelium, pancreatic ductal cell, buccal mucosa cell
HYLS1	205	ubiquitous	yes	oocyte, secondary oocyte, sperm
CEP120	254	ubiquitous	yes	calcaneal tendon, epithelial cell of pancreas, mucosa of paranasal sinus
ARL3	299	ubiquitous	marker	bronchial epithelial cell, mucosa of paranasal sinus, epithelium of bronchus
BST1	185	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
USH2A	30	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell
RLIM	256	ubiquitous	marker	middle temporal gyrus, cartilage tissue, adrenal tissue
CARD9	172	broad	marker	monocyte, mononuclear cell, leukocyte
RCOR1	288	ubiquitous	marker	secondary oocyte, esophagus squamous epithelium, epithelium of esophagus
ATP6V0A2	239	ubiquitous	marker	skin of leg, sural nerve, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 201.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHD7	4,819
PMPCA	3,679
CARD9	3,636
OFD1	2,878
RCOR1	2,806
CEP290	2,778
ARL3	2,651
PDPR	2,635
ARL13B	2,558
EIF2B1	2,548

Intra-cohort edges

A	B	Sources
AHI1	ARL13B	string_interaction
AHI1	B9D1	string_interaction
AHI1	B9D2	string_interaction
AHI1	CC2D2A	biogrid_interaction, intact, string_interaction
AHI1	CEP290	string_interaction
AHI1	CEP41	string_interaction
AHI1	CPLANE1	string_interaction
AHI1	CSPP1	string_interaction
AHI1	KIAA0753	string_interaction
AHI1	OFD1	biogrid_interaction, intact, string_interaction
AHI1	RPGRIP1L	string_interaction
AHI1	TCTN1	string_interaction
AHI1	TCTN2	string_interaction
AHI1	TMEM216	string_interaction
AHI1	TMEM231	string_interaction
AHI1	TMEM67	string_interaction
ARL13B	C2CD3	string_interaction
ARL13B	CC2D2A	string_interaction
ARL13B	CEP290	string_interaction
ARL13B	CEP41	string_interaction
ARL13B	IFT74	biogrid_interaction
ARL13B	INPP5E	string_interaction
ARL13B	KATNIP	string_interaction
ARL13B	OFD1	string_interaction
ARL13B	RPGRIP1L	string_interaction
ARL13B	TMEM17	biogrid_interaction, intact
ARL13B	TMEM216	string_interaction
ARL13B	TMEM67	string_interaction
ARMC9	CEP104	intact, string_interaction
ARMC9	CEP41	string_interaction
ARMC9	CSPP1	intact, string_interaction
ARMC9	KATNIP	string_interaction
ARMC9	TOGARAM1	intact, string_interaction
B9D1	B9D2	biogrid_interaction, intact, string_interaction
B9D1	CC2D2A	biogrid_interaction, intact, string_interaction
B9D1	CEP290	string_interaction
B9D1	CEP41	string_interaction
B9D1	HYLS1	string_interaction
B9D1	MKS1	biogrid_interaction, intact, string_interaction
B9D1	RPGRIP1L	string_interaction
B9D1	TCTN1	intact, string_interaction
B9D1	TCTN2	intact, string_interaction
B9D1	TMEM17	intact, string_interaction
B9D1	TMEM216	string_interaction
B9D1	TMEM218	string_interaction
B9D1	TMEM231	biogrid_interaction, intact, string_interaction
B9D1	TMEM237	string_interaction
B9D1	TMEM67	string_interaction
B9D2	CC2D2A	biogrid_interaction, intact, string_interaction
B9D2	CEP290	string_interaction

Structural data

PDB: 23 · AlphaFold-only: 41 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RCOR1	Q9UKL0	102
FTO	Q9C0B1	28
EIF2B1	Q14232	27
SUFU	Q9UMX1	10
CARD9	Q9H257	8
SLC30A7	Q8NEW0	7
BST1	Q10588	6
KIF7	Q2M1P5	5
CEP120	Q8N960	4
RLIM	Q9NVW2	3
CHD7	Q9P2D1	3
CEP104	O60308	2
PDPR	Q8NCN5	2
CBY1	Q9Y3M2	1
INPP5E	Q9NRR6	1
AHI1	Q8N157	1
TMEM67	Q5HYA8	1
ATXN3L	Q9H3M9	1
WDPCP	O95876	1
LRRC34	Q8IZ02	1
RPGRIP1L	Q68CZ1	1
CPSF7	Q8N684	1
IFT172	Q9UG01	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GDPD1	Q8N9F7	96.12
ARL3	P36405	92.73
RLIG1	Q8N999	92.03
B9D2	Q9BPU9	89.79
TMEM216	Q9P0N5	89.18
PGAP1	Q75T13	89.15
TMEM231	Q9H6L2	88.65
PMPCA	Q10713	88.46
TMEM218	A2RU14	87.79
TMEM17	Q86X19	86.20
PDP1	Q9P0J1	83.41
B9D1	Q9UPM9	83.05
ATP6V0A2	Q9Y487	81.94
IFT74	Q96LB3	81.21
TCTN1	Q2MV58	78.10
IFT38	Q96AJ1	78.02
PIBF1	Q8WXW3	77.70
EGFL7	Q9UHF1	76.11
EXOC8	Q8IYI6	74.86
TCTN2	Q96GX1	74.71
MKS1	Q9NXB0	74.05
PLPP6	Q8IY26	73.75
ARL13B	Q3SXY8	72.92
ARMC9	Q7Z3E5	71.71
ABCA2	Q9BZC7	71.46
CEP41	Q9BYV8	71.06
CC2D2A	Q9P2K1	69.46
EVPLL	A8MZ36	69.26
OFD1	O75665	68.41
HYLS1	Q96M11	66.11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 107. Enrichment computed across 65 evidence-associated genes (41 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 41 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring of the basal body to the plasma membrane	14	38.6×	2e-17	CEP41, AHI1, B9D1, TCTN2, TCTN1, TMEM67, MKS1, C2CD3 (+6 more)
Cilium Assembly	14	37.1×	2e-17	CEP41, INPP5E, AHI1, B9D1, ARL13B, TCTN2, TCTN1, TMEM67 (+6 more)
Organelle biogenesis and maintenance	14	22.5×	2e-14	CEP41, INPP5E, AHI1, B9D1, ARL13B, TCTN2, TCTN1, TMEM67 (+6 more)
Hedgehog ‘off’ state	6	26.1×	3e-06	MKS1, SUFU, OFD1, RPGRIP1L, IFT172, KIF7
ARL13B-mediated ciliary trafficking of INPP5E	2	185.7×	8e-04	INPP5E, ARL13B
Cargo trafficking to the periciliary membrane	3	18.2×	0.010	INPP5E, ARL13B, ARL3
Intraflagellar transport	3	14.7×	0.017	IFT38, IFT74, IFT172
Regulation of pyruvate dehydrogenase (PDH) complex	2	34.8×	0.017	PDPR, PDP1
Signaling by Hedgehog	3	13.5×	0.017	MKS1, SUFU, KIF7
Loss of Nlp from mitotic centrosomes	3	11.6×	0.021	CEP41, OFD1, CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	3	11.6×	0.021	CEP41, OFD1, CEP290
AURKA Activation by TPX2	3	11.1×	0.022	CEP41, OFD1, CEP290
Recruitment of mitotic centrosome proteins and complexes	3	9.9×	0.028	CEP41, OFD1, CEP290
Regulation of PLK1 Activity at G2/M Transition	3	9.3×	0.031	CEP41, OFD1, CEP290
Recruitment of NuMA to mitotic centrosomes	3	8.5×	0.037	CEP41, OFD1, CEP290
Centrosome maturation	2	12.4×	0.076	CEP41, CEP290
Trafficking of myristoylated proteins to the cilium	1	55.7×	0.112	ARL3
Mitotic Prometaphase	3	5.1×	0.126	CEP41, B9D2, CEP290
Glycerophospholipid catabolism	1	39.8×	0.127	GDPD1
Reversal of alkylation damage by DNA dioxygenases	1	39.8×	0.127	FTO
M Phase	3	4.8×	0.127	CEP41, B9D2, CEP290
Hedgehog ‘on’ state	2	7.7×	0.133	SUFU, KIF7
Attachment of GPI anchor to uPAR	1	30.9×	0.142	PGAP1
Recycling of eIF2:GDP	1	30.9×	0.142	EIF2B1
Josephin domain DUBs	1	23.2×	0.167	ATXN3L
Mitotic G2-G2/M phases	2	6.2×	0.167	CEP41, CEP290
G2/M Transition	2	6.2×	0.167	CEP41, CEP290
Lanosterol biosynthesis	1	18.6×	0.195	PLPP6
Cell Cycle, Mitotic	3	3.5×	0.195	CEP41, B9D2, CEP290
Synthesis of PIPs at the Golgi membrane	1	15.5×	0.217	INPP5E

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 62 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cilium assembly	32	38.0×	2e-41	CEP41, CBY1, TMEM237, KIAA0586, ARMC9, INPP5E, AHI1, PIBF1 (+24 more)
non-motile cilium assembly	12	56.2×	3e-16	PIBF1, ARL13B, MKS1, TOGARAM1, IFT74, C2CD3, TMEM216, TMEM17 (+4 more)
smoothened signaling pathway	11	32.1×	4e-12	KIAA0586, B9D1, ARL13B, TCTN2, IFT38, TMEM17, WDPCP, CC2D2A (+3 more)
camera-type eye development	5	28.9×	8e-05	B9D1, WDPCP, CEP290, CC2D2A, TMEM231
protein localization to ciliary transition zone	3	116.5×	1e-04	TCTN2, TCTN1, CC2D2A
embryonic digit morphogenesis	5	24.3×	1e-04	B9D1, MKS1, C2CD3, WDPCP, TMEM231
regulation of smoothened signaling pathway	4	40.3×	2e-04	TCTN1, MKS1, C2CD3, RPGRIP1L
heart looping	5	21.6×	2e-04	ARL13B, SUFU, IFT38, C2CD3, IFT172
axoneme assembly	4	35.1×	2e-04	IFT38, TOGARAM1, OFD1, CC2D2A
positive regulation of pyruvate decarboxylation to acetyl-CoA	2	271.8×	5e-04	PDPR, PDP1
positive regulation of smoothened signaling pathway	4	27.2×	5e-04	ARMC9, TMEM216, IFT172, KIF7
neural tube closure	5	15.1×	6e-04	MKS1, SUFU, IFT38, CC2D2A, IFT172
RNA repair	2	181.2×	0.001	FTO, RLIG1
intraciliary anterograde transport	3	42.9×	0.001	IFT38, IFT74, IFT172
dorsal/ventral neural tube patterning	3	38.8×	0.002	TCTN1, MKS1, SUFU
kidney development	5	11.3×	0.002	WDPCP, CEP290, RPGRIP1L, CC2D2A, ARL3
protein localization to centrosome	3	32.6×	0.002	PIBF1, C2CD3, KIAA0753
determination of left/right symmetry	4	16.5×	0.002	MKS1, IFT74, RPGRIP1L, CC2D2A
motile cilium assembly	3	28.1×	0.003	AHI1, MKS1, CC2D2A
intraciliary transport	3	27.2×	0.003	WDPCP, IFT172, ARL3
neural tube patterning	2	90.6×	0.004	ARL13B, RPGRIP1L
in utero embryonic development	6	7.0×	0.004	B9D1, TCTN1, CHD7, C2CD3, RPGRIP1L, TMEM231
nose development	2	77.7×	0.004	CHD7, RPGRIP1L
regulation of establishment of protein localization	2	77.7×	0.004	KIAA0586, CEP290
negative regulation of smoothened signaling pathway	3	22.0×	0.005	SUFU, IFT172, KIF7
neuroepithelial cell differentiation	2	49.4×	0.011	B9D1, TMEM231
cardiac septum morphogenesis	2	38.8×	0.016	MKS1, CHD7
left/right axis specification	2	38.8×	0.016	ARL13B, IFT172
vasculature development	2	36.2×	0.018	B9D1, TMEM231
establishment of planar polarity	2	34.0×	0.020	WDPCP, RPGRIP1L

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 62

Druggability breadth: 12 of 65 evidence-associated genes (18%) 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
RCOR1	OSIMERTINIB
FTO	FLUORESCEIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FTO	18	4
RCOR1	4	4
CPSF7	1	2
CEP41	0	0
CBY1	0	0
TMEM237	0	0
PMPCA	0	0
KIAA0586	0	0
ARMC9	0	0
INPP5E	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OSIMERTINIB	4	RCOR1
TRANYLCYPROMINE	4	RCOR1
COLISTIN	4	RCOR1
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
NAFAMOSTAT MESYLATE	3	FTO
DIACEREIN	3	FTO
AMONAFIDE	3	FTO
QUERCETIN	3	FTO
IADADEMSTAT	2	RCOR1
METIZOLINE	2	FTO
LUTEOLIN	2	FTO
FENOBAM ANHYDROUS	2	FTO
FISETIN	2	FTO
MITONAFIDE	2	FTO
BAICALEIN	2	FTO
MOLIBRESIB	2	CPSF7
KAEMPFEROL	1	FTO

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
FTO	153	Binding:153
RCOR1	64	Binding:64
CPSF7	7	Binding:7
KIF7	5	Binding:5
BST1	3	Binding:3
ATXN3L	2	Binding:2
PMPCA	1	Binding:1
CSPP1	1	Binding:1
SUFU	1	Binding:1
SLC30A7	1	Binding:1
EIF2B1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PMPCA	3.4.24.64	mitochondrial processing peptidase
INPP5E	3.1.3.36	phosphoinositide 5-phosphatase
ATP6V0A2	7.1.2.1	P-type H+-exporting transporter
GDPD1	3.1.4.46	glycerophosphodiester phosphodiesterase
FTO	1.14.11.53	mRNA N6-methyladenine demethylase
PDPR	3.1.3.43	[pyruvate dehydrogenase (acetyl-transferring)]-phosphatase
PDP1	3.1.3.43	[pyruvate dehydrogenase (acetyl-transferring)]-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FTO	153

Pharmacogenomics

Cohort genes with a PharmGKB record: 64; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

23 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)
OSIMERTINIB	4	RCOR1
TRANYLCYPROMINE	4	RCOR1
COLISTIN	4	RCOR1
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
NAFAMOSTAT MESYLATE	3	FTO
DIACEREIN	3	FTO
AMONAFIDE	3	FTO
QUERCETIN	3	FTO
IADADEMSTAT	2	RCOR1
METIZOLINE	2	FTO
LUTEOLIN	2	FTO
FENOBAM ANHYDROUS	2	FTO
FISETIN	2	FTO
MITONAFIDE	2	FTO
BAICALEIN	2	FTO
MOLIBRESIB	2	CPSF7
KAEMPFEROL	1	FTO

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RCOR1, FTO
B	Phased (≥1) drug, not yet approved	1	CPSF7
C	Druggable family + PDB, no drug	2	INPP5E, PDPR
D	Druggable family + AlphaFold only, no drug	7	PMPCA, USH2A, ATP6V0A2, GDPD1, CC2D2A, ABCA2, PDP1
E	Difficult family or no structure, no drug	53	CEP41, CBY1, TMEM237, KIAA0586, ARMC9, AHI1, PIBF1, B9D1, CEP104, ARL13B (+43 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CEP41	0	—
CBY1	0	—
TMEM237	0	—
PMPCA	1	—
KIAA0586	0	—
ARMC9	0	—
INPP5E	0	—
AHI1	0	—
PIBF1	0	—
B9D1	0	—
CEP104	0	—
ARL13B	0	—
TCTN2	0	—
CPLANE1	0	—
TCTN1	0	—
CSPP1	1	—
TMEM67	0	—
KATNIP	0	—
MKS1	0	—
SUFU	1	—
SLC30A7	1	—
HYLS1	0	—
CEP120	0	—
ARL3	0	—
BST1	3	—
USH2A	0	—
RLIM	0	—
CARD9	0	—
ATP6V0A2	0	—
IFT38	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)