Bardet-Biedl syndrome

Summary

Bardet-Biedl syndrome (MONDO:0015229) is a disease (an umbrella term covering 22 Mondo subtypes) with 54 cohort genes and 17 clinical trials. The dominant Reactome pathway is BBSome-mediated cargo-targeting to cilium (13 cohort genes). Top therapeutic interventions include setmelanotide and metformin.

At a glance

• Prevalence: 1-9 / 100 000 (Specific population) [Orphanet-validated]
• Umbrella term: 22 Mondo subtypes
• Cohort genes: 54
• ClinVar variants: 7,996
• Phenotypes (HPO): 95
• Clinical trials: 17

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.5	Europe	Validated
Point prevalence	1-9 / 100 000	7.4	Specific population	Validated
Point prevalence	1-9 / 1 000 000	0.64	Tunisia	Validated
Point prevalence	1-9 / 100 000	1	United States	Validated

Signs & symptoms

Clinical features (HPO)

95 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000556	Retinal dystrophy	Obligate (100%)
HP:0000548	Cone/cone-rod dystrophy	Very frequent (80-99%)
HP:0001513	Obesity	Very frequent (80-99%)
HP:0008915	Childhood-onset truncal obesity	Very frequent (80-99%)
HP:0012758	Neurodevelopmental delay	Very frequent (80-99%)
HP:0000119	Abnormality of the genitourinary system	Frequent (30-79%)
HP:0000135	Hypogonadism	Frequent (30-79%)
HP:0000163	Abnormal oral cavity morphology	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000512	Abnormal electroretinogram	Frequent (30-79%)
HP:0000551	Color vision defect	Frequent (30-79%)
HP:0000613	Photophobia	Frequent (30-79%)
HP:0000618	Blindness	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000662	Nyctalopia	Frequent (30-79%)
HP:0000668	Hypodontia	Frequent (30-79%)
HP:0000678	Dental crowding	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0000717	Autism	Frequent (30-79%)
HP:0000736	Short attention span	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001328	Specific learning disability	Frequent (30-79%)
HP:0002155	Hypertriglyceridemia	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0003233	Decreased HDL cholesterol concentration	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004408	Abnormality of the sense of smell	Frequent (30-79%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0008724	Hypoplasia of the ovary	Frequent (30-79%)
HP:0008736	Hypoplasia of penis	Frequent (30-79%)
HP:0012622	Chronic kidney disease	Frequent (30-79%)
HP:0025691	Impaired fasting glucose	Frequent (30-79%)
HP:0100259	Postaxial polydactyly	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0000011	Neurogenic bladder	Occasional (5-29%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000076	Vesicoureteral reflux	Occasional (5-29%)
HP:0000085	Horseshoe kidney	Occasional (5-29%)
HP:0000100	Nephrotic syndrome	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000147	Polycystic ovaries	Occasional (5-29%)
HP:0000278	Retrognathia	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000388	Otitis media	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000426	Prominent nasal bridge	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome
Mondo ID	MONDO:0015229
MeSH	D020788
OMIM	209900
Orphanet	110
DOID	DOID:1935
ICD-11	255526264
NCIT	C118632
SNOMED CT	5619004
UMLS	C0752166
MedGen	156019
GARD	0006866
MedDRA	10056715
NORD	838
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome · BBS

Data availability: 7,996 ClinVar variants · 25 GenCC gene-disease records · 81 cell lines.

Disease family

An umbrella term covering 22 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bardet-Biedl 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, 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, 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 (22): Bardet-Biedl syndrome 1, Bardet-Biedl syndrome 3, Bardet-Biedl syndrome 6, Bardet-Biedl syndrome 2, Bardet-Biedl syndrome 4, Bardet-Biedl syndrome 5, Bardet-Biedl syndrome 7, Bardet-Biedl syndrome 8, Bardet-Biedl syndrome 9, Bardet-Biedl syndrome 10, Bardet-Biedl syndrome 11, Bardet-Biedl syndrome 12, Bardet-Biedl syndrome 13, Bardet-Biedl syndrome 14, Bardet-Biedl syndrome 15, Bardet-Biedl syndrome 16, Bardet-Biedl syndrome 17, Bardet-Biedl syndrome 18, Bardet-Biedl syndrome 19, Bardet-Biedl syndrome 22, Bardet-Biedl syndrome 20, bardet-biedl syndrome 21

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:

319 uncertain significance, 171 likely benign, 44 pathogenic, 30 pathogenic/likely pathogenic, 21 conflicting classifications of pathogenicity, 12 likely pathogenic, 2 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069572	NC_000009.11:g.(?119380583)(119495822_?)del	ASTN2	Pathogenic	criteria provided, single submitter
1072407	NM_012210.4(TRIM32):c.1185dup (p.Gln396fs)	ASTN2	Pathogenic	criteria provided, single submitter
1076771	NM_012210.4(TRIM32):c.542_543insAAAGGTA (p.Tyr181Ter)	ASTN2	Pathogenic	criteria provided, single submitter
1037244	NM_024649.5(BBS1):c.1181-9C>G	BBS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069654	NM_024649.5(BBS1):c.1025dup (p.Leu343fs)	BBS1	Pathogenic	criteria provided, single submitter
1069863	NC_000011.9:g.(?66296758)(66307295_?)del	BBS1	Pathogenic	criteria provided, single submitter
1069864	NC_000011.9:g.(?66283154)(66287229_?)del	BBS1	Pathogenic	criteria provided, single submitter
1069865	NC_000011.9:g.(?66288721)(66293683_?)del	BBS1	Pathogenic	criteria provided, single submitter
1070846	NM_024649.5(BBS1):c.421C>T (p.Gln141Ter)	BBS1	Pathogenic	criteria provided, single submitter
1074464	NM_024649.5(BBS1):c.382C>T (p.Gln128Ter)	BBS1	Pathogenic	criteria provided, multiple submitters, no conflicts
1074693	NM_024649.5(BBS1):c.1261C>T (p.Gln421Ter)	BBS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075093	NM_024649.5(BBS1):c.830G>A (p.Arg277Lys)	BBS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075743	NC_000011.9:g.(?66278111)(66299528_?)del	BBS1	Pathogenic	criteria provided, single submitter
1075744	NC_000011.9:g.(?66291682)(66293673_?)del	BBS1	Pathogenic	criteria provided, single submitter
1076842	NM_024649.5(BBS1):c.1657G>T (p.Glu553Ter)	BBS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029918	NM_024685.4(BBS10):c.1365T>G (p.Tyr455Ter)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
1069258	NM_024685.4(BBS10):c.439C>T (p.Gln147Ter)	BBS10	Pathogenic	criteria provided, single submitter
1070972	NM_024685.4(BBS10):c.455_456del (p.His152fs)	BBS10	Pathogenic	criteria provided, single submitter
1072493	NM_024685.4(BBS10):c.313_314del (p.Lys105fs)	BBS10	Pathogenic	criteria provided, single submitter
1073736	NM_024685.4(BBS10):c.1654G>T (p.Gly552Ter)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075020	NM_024685.4(BBS10):c.35dup (p.Ala13fs)	BBS10	Pathogenic	criteria provided, single submitter
1043917	NM_152618.3(BBS12):c.1627G>A (p.Glu543Lys)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069432	NM_152618.3(BBS12):c.1827C>G (p.Tyr609Ter)	BBS12	Pathogenic	criteria provided, single submitter
1069707	NM_152618.3(BBS12):c.445C>T (p.Gln149Ter)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069739	NM_152618.3(BBS12):c.694dup (p.Ile232fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069940	NM_152618.3(BBS12):c.2053C>T (p.Gln685Ter)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070029	NM_152618.3(BBS12):c.590_591del (p.Ser196_Tyr197insTer)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070921	NM_152618.3(BBS12):c.1705del (p.Leu569fs)	BBS12	Pathogenic	criteria provided, single submitter
1071069	NM_152618.3(BBS12):c.1663_1667del (p.Glu555fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071214	NM_152618.3(BBS12):c.398del (p.Pro133fs)	BBS12	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 179 · Orphanet: 103 · 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
ARL6	Definitive	Autosomal recessive	Bardet-Biedl syndrome 3	9
BBS1	Definitive	Autosomal recessive	Bardet-Biedl syndrome 1	7
BBS10	Definitive	Autosomal recessive	Bardet-Biedl syndrome 10	6
BBS12	Definitive	Autosomal recessive	Bardet-Biedl syndrome 12	7
BBS2	Definitive	Autosomal recessive	Bardet-Biedl syndrome 2	10
BBS4	Definitive	Autosomal recessive	Bardet-Biedl syndrome 4	5
BBS5	Definitive	Autosomal recessive	Bardet-Biedl syndrome 5	7
BBS7	Definitive	Autosomal recessive	Bardet-Biedl syndrome 7	5
BBS9	Definitive	Autosomal recessive	Bardet-Biedl syndrome 9	5
IFT74	Definitive	Autosomal recessive	Bardet-Biedl syndrome 22	5
MKS1	Definitive	Autosomal recessive	Bardet-Biedl syndrome 13	11
TTC8	Definitive	Autosomal recessive	Bardet-Biedl syndrome 8	9
WDPCP	Definitive	Autosomal recessive	Bardet-Biedl syndrome 15	7
BBIP1	Strong	Autosomal recessive	Bardet-Biedl syndrome 18	6
CEP290	Strong	Autosomal recessive	Bardet-Biedl syndrome 14	10
IFT172	Strong	Autosomal recessive	Bardet-Biedl syndrome 20	12
IFT27	Strong	Autosomal recessive	Bardet-Biedl syndrome 19	5
LZTFL1	Strong	Autosomal recessive	Bardet-Biedl syndrome 17	5
MKKS	Strong	Autosomal recessive	Bardet-Biedl syndrome 6	7
SDCCAG8	Strong	Autosomal recessive	Bardet-Biedl syndrome 16	9
TRIM32	Strong	Autosomal recessive	Bardet-Biedl syndrome 11	8
CEP19	Supportive	Autosomal recessive	Bardet-Biedl syndrome	5
NPHP1	Supportive	Autosomal recessive	Bardet-Biedl syndrome	9
SCAPER	Supportive	Autosomal recessive	Bardet-Biedl syndrome	6
SCLT1	Limited	Autosomal recessive	Bardet-Biedl syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SDCCAG8	Orphanet:110	Bardet-Biedl syndrome
SDCCAG8	Orphanet:3156	Senior-Loken syndrome
ARL6	Orphanet:110	Bardet-Biedl syndrome
ARL6	Orphanet:791	Retinitis pigmentosa
IFT27	Orphanet:110	Bardet-Biedl syndrome
BBS7	Orphanet:110	Bardet-Biedl syndrome
TTC8	Orphanet:110	Bardet-Biedl syndrome
TTC8	Orphanet:791	Retinitis pigmentosa
IFT74	Orphanet:110	Bardet-Biedl syndrome
IFT74	Orphanet:137893	Male infertility due to large-headed multiflagellar polyploid spermatozoa
IFT74	Orphanet:475	Isolated Joubert syndrome
BBS10	Orphanet:110	Bardet-Biedl syndrome
SCLT1	Orphanet:110	Bardet-Biedl syndrome
BBS12	Orphanet:110	Bardet-Biedl syndrome
WDPCP	Orphanet:110	Bardet-Biedl syndrome
WDPCP	Orphanet:1338	Heart defect-tongue hamartoma-polysyndactyly syndrome
CEP19	Orphanet:110	Bardet-Biedl syndrome
CEP19	Orphanet:397615	Obesity due to CEP19 deficiency
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis
BBS9	Orphanet:110	Bardet-Biedl syndrome
IFT172	Orphanet:110	Bardet-Biedl syndrome
IFT172	Orphanet:140969	Saldino-Mainzer syndrome
IFT172	Orphanet:474	Jeune syndrome
IFT172	Orphanet:791	Retinitis pigmentosa
LZTFL1	Orphanet:110	Bardet-Biedl syndrome
MKKS	Orphanet:110	Bardet-Biedl syndrome
MKKS	Orphanet:2473	McKusick-Kaufman 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
NPHP1	Orphanet:110	Bardet-Biedl syndrome
NPHP1	Orphanet:220497	Joubert syndrome with renal defect
NPHP1	Orphanet:3156	Senior-Loken syndrome
NPHP1	Orphanet:93592	Juvenile nephronophthisis
BBS1	Orphanet:110	Bardet-Biedl syndrome
BBS1	Orphanet:791	Retinitis pigmentosa
BBS2	Orphanet:110	Bardet-Biedl syndrome
BBS2	Orphanet:791	Retinitis pigmentosa
BBS4	Orphanet:110	Bardet-Biedl syndrome
BBS5	Orphanet:110	Bardet-Biedl syndrome
SCAPER	Orphanet:110	Bardet-Biedl syndrome
SCAPER	Orphanet:791	Retinitis pigmentosa
TRIM32	Orphanet:110	Bardet-Biedl syndrome
TRIM32	Orphanet:1878	TRIM32-related limb-girdle muscular dystrophy R8
BBIP1	Orphanet:110	Bardet-Biedl syndrome

Cohort genes → proteins

54 cohort genes, 53 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	54

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SDCCAG8	HGNC:10671	ENSG00000054282	Q86SQ7	Serologically defined colon cancer antigen 8	gencc,clinvar
ARL6	HGNC:13210	ENSG00000113966	Q9H0F7	ADP-ribosylation factor-like protein 6	gencc,clinvar
IFT27	HGNC:18626	ENSG00000100360	Q9BW83	Intraflagellar transport protein 27 homolog	gencc,clinvar
BBS7	HGNC:18758	ENSG00000138686	Q8IWZ6	BBSome complex member BBS7	gencc,clinvar
TTC8	HGNC:20087	ENSG00000165533	Q8TAM2	Tetratricopeptide repeat protein 8	gencc,clinvar
IFT74	HGNC:21424	ENSG00000096872	Q96LB3	Intraflagellar transport protein 74 homolog	gencc,clinvar
BBS10	HGNC:26291	ENSG00000179941	Q8TAM1	BBSome complex assembly protein BBS10	gencc,clinvar
SCLT1	HGNC:26406	ENSG00000151466	Q96NL6	Sodium channel and clathrin linker 1	gencc,clinvar
BBS12	HGNC:26648	ENSG00000181004	Q6ZW61	Chaperonin-containing T-complex member BBS12	gencc,clinvar
WDPCP	HGNC:28027	ENSG00000143951	O95876	WD repeat-containing and planar cell polarity effector protein fritz homolog	gencc,clinvar
CEP19	HGNC:28209	ENSG00000174007	Q96LK0	Centrosomal protein of 19 kDa	gencc,clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	gencc,clinvar
BBS9	HGNC:30000	ENSG00000122507	Q3SYG4	Protein PTHB1	gencc,clinvar
IFT172	HGNC:30391	ENSG00000138002	Q9UG01	Intraflagellar transport protein 172 homolog	gencc,clinvar
LZTFL1	HGNC:6741	ENSG00000163818	Q9NQ48	Leucine zipper transcription factor-like protein 1	gencc,clinvar
MKKS	HGNC:7108	ENSG00000125863	Q9NPJ1	Molecular chaperone MKKS	gencc,clinvar
MKS1	HGNC:7121	ENSG00000011143	Q9NXB0	Tectonic-like complex member MKS1	gencc,clinvar
NPHP1	HGNC:7905	ENSG00000144061	O15259	Nephrocystin-1	gencc,clinvar
BBS1	HGNC:966	ENSG00000174483	Q8NFJ9	BBSome complex member BBS1	gencc,clinvar
BBS2	HGNC:967	ENSG00000125124	Q9BXC9	BBSome complex member BBS2	gencc,clinvar
BBS4	HGNC:969	ENSG00000140463	Q96RK4	BBSome complex member BBS4	gencc,clinvar
BBS5	HGNC:970	ENSG00000163093	Q8N3I7	BBSome complex member BBS5	gencc,clinvar
SCAPER	HGNC:13081	ENSG00000140386	Q9BY12	S phase cyclin A-associated protein in the endoplasmic reticulum	gencc
TRIM32	HGNC:16380	ENSG00000119401	Q13049	E3 ubiquitin-protein ligase TRIM32	gencc
BBIP1	HGNC:28093	ENSG00000214413	A8MTZ0	BBSome-interacting protein 1	gencc
USH2A	HGNC:12601	ENSG00000042781	O75445	Usherin	clinvar
RPGRIP1	HGNC:13436	ENSG00000092200	Q96KN7	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	clinvar
TSPOAP1	HGNC:16831	ENSG00000005379	O95153	Peripheral-type benzodiazepine receptor-associated protein 1	clinvar
ASTN2	HGNC:17021	ENSG00000148219	O75129	Astrotactin-2	clinvar
IFT57	HGNC:17367	ENSG00000114446	Q9NWB7	Intraflagellar transport protein 57 homolog	clinvar
WDR19	HGNC:18340	ENSG00000157796	Q8NEZ3	WD repeat-containing protein 19	clinvar
IMPG2	HGNC:18362	ENSG00000081148	Q9BZV3	Interphotoreceptor matrix proteoglycan 2	clinvar
NPHP4	HGNC:19104	ENSG00000131697	O75161	Nephrocystin-4	clinvar
TRAPPC3	HGNC:19942	ENSG00000054116	O43617	Trafficking protein particle complex subunit 3	clinvar
COMT	HGNC:2228	ENSG00000093010	P21964	Catechol O-methyltransferase	clinvar
PHLDB1	HGNC:23697	ENSG00000019144	Q86UU1	Pleckstrin homology-like domain family B member 1	clinvar
ARL6IP6	HGNC:24048	ENSG00000177917	Q8N6S5	ADP-ribosylation factor-like protein 6-interacting protein 6	clinvar
AP5B1	HGNC:25104	ENSG00000254470	Q2VPB7	AP-5 complex subunit beta-1	clinvar
ADPGK	HGNC:25250	ENSG00000159322	Q9BRR6	ADP-dependent glucokinase	clinvar
ZDHHC24	HGNC:27387	ENSG00000174165	Q6UX98	Probable palmitoyltransferase ZDHHC24	clinvar
CCDC28B	HGNC:28163	ENSG00000160050	Q9BUN5	Coiled-coil domain-containing protein 28B	clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar
IQCB1	HGNC:28949	ENSG00000173226	Q15051	IQ calmodulin-binding motif-containing protein 1	clinvar
RPGRIP1L	HGNC:29168	ENSG00000103494	Q68CZ1	Protein fantom	clinvar
ABCB11	HGNC:42	ENSG00000073734	O95342	Bile salt export pump	clinvar
ALMS1	HGNC:428	ENSG00000116127	Q8TCU4	Centrosome-associated protein ALMS1	clinvar
GLI1	HGNC:4317	ENSG00000111087	P08151	Zinc finger protein GLI1	clinvar
GLI2	HGNC:4318	ENSG00000074047	P10070	Zinc finger protein GLI2	clinvar
ADGRG1	HGNC:4512	ENSG00000205336	Q9Y653	Adhesion G-protein coupled receptor G1	clinvar
HTR2B	HGNC:5294	ENSG00000135914	P41595	5-hydroxytryptamine receptor 2B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SDCCAG8	Serologically defined colon cancer antigen 8	Plays a role in the establishment of cell polarity and epithelial lumen formation.
ARL6	ADP-ribosylation factor-like protein 6	Involved in membrane protein trafficking at the base of the ciliary organelle.
IFT27	Intraflagellar transport protein 27 homolog	Small GTPase-like component of the intraflagellar transport (IFT) complex B that promotes the exit of the BBSome complex from cilia via its interaction with ARL6.
BBS7	BBSome complex member BBS7	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
TTC8	Tetratricopeptide repeat protein 8	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
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.
BBS10	BBSome complex assembly protein BBS10	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.
SCLT1	Sodium channel and clathrin linker 1	Adapter protein that links SCN10A to clathrin.
BBS12	Chaperonin-containing T-complex member BBS12	Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis.
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.
CEP19	Centrosomal protein of 19 kDa	Required for ciliation.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
BBS9	Protein PTHB1	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
IFT172	Intraflagellar transport protein 172 homolog	Required for the maintenance and formation of cilia.
LZTFL1	Leucine zipper transcription factor-like protein 1	Regulates ciliary localization of the BBSome complex.
MKKS	Molecular chaperone MKKS	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.
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.
NPHP1	Nephrocystin-1	Together with BCAR1 it may play a role in the control of epithelial cell polarity.
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.
BBS2	BBSome complex member BBS2	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
BBS4	BBSome complex member BBS4	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
BBS5	BBSome complex member BBS5	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
SCAPER	S phase cyclin A-associated protein in the endoplasmic reticulum	CCNA2/CDK2 regulatory protein that transiently maintains CCNA2 in the cytoplasm.
TRIM32	E3 ubiquitin-protein ligase TRIM32	E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy.
BBIP1	BBSome-interacting protein 1	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
USH2A	Usherin	Involved in hearing and vision as member of the USH2 complex.
RPGRIP1	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	May function as scaffolding protein.
TSPOAP1	Peripheral-type benzodiazepine receptor-associated protein 1	Required for synaptic transmission regulation.
ASTN2	Astrotactin-2	Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons.
IFT57	Intraflagellar transport protein 57 homolog	Required for the formation of cilia.
WDR19	WD repeat-containing protein 19	As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly.
IMPG2	Interphotoreceptor matrix proteoglycan 2	Chondroitin sulfate- and hyaluronan-binding proteoglycan involved in the organization of interphotoreceptor matrix; may participate in the maturation and maintenance of the light-sensitive photoreceptor outer segment.
NPHP4	Nephrocystin-4	Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module.
TRAPPC3	Trafficking protein particle complex subunit 3	May play a role in vesicular transport from endoplasmic reticulum to Golgi.
COMT	Catechol O-methyltransferase	Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones.
AP5B1	AP-5 complex subunit beta-1	As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport.
ADPGK	ADP-dependent glucokinase	Catalyzes the phosphorylation of D-glucose to D-glucose 6-phosphate using ADP as the phosphate donor.
ZDHHC24	Probable palmitoyltransferase ZDHHC24	Probable palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates.
CCDC28B	Coiled-coil domain-containing protein 28B	Involved in ciliogenesis.
TMEM67	Meckelin	Required for ciliary structure and function.
IQCB1	IQ calmodulin-binding motif-containing protein 1	Involved in ciliogenesis.
RPGRIP1L	Protein fantom	Negatively regulates signaling through the G-protein coupled thromboxane A2 receptor (TBXA2R).
ABCB11	Bile salt export pump	Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeosta…
ALMS1	Centrosome-associated protein ALMS1	Involved in PCM1-dependent intracellular transport.
GLI1	Zinc finger protein GLI1	Acts as a transcriptional activator.
GLI2	Zinc finger protein GLI2	Functions as a transcription regulator in the hedgehog (Hh) pathway.
ADGRG1	Adhesion G-protein coupled receptor G1	Adhesion G-protein coupled receptor (aGPCR) for steroid hormone 17alpha-hydroxypregnenolone (17-OH), which is involved in cell adhesion and cell-cell interactions.
HTR2B	5-hydroxytryptamine receptor 2B	G-protein coupled receptor for 5-hydroxytryptamine (serotonin).
JAG1	Protein jagged-1	Ligand for multiple Notch receptors and involved in the mediation of Notch signaling.
NPHP3	Nephrocystin-3	Required for normal ciliary development and function.

Protein-family classification

Druggable: 8 · Difficult: 12 · Unknown: 34 · 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
Complement	1	5.0×	0.549
Scaffold/PPI	6	1.9×	0.549
Other/Unknown	34	1.1×	0.549
Transporter	1	1.4×	0.856
Antibody/Immunoglobulin	2	1.1×	0.856
Transcription factor	6	0.9×	0.856
GPCR	2	0.9×	0.856
Kinase	1	0.5×	0.971
Enzyme (other)	1	0.2×	0.991

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDCCAG8	Other/Unknown	no		SDCCAG8
ARL6	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF
IFT27	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase
BBS7	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, Bardet-Biedl_syndrome_7_prot, WD40_repeat_dom_sf
TTC8	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, BBS8
IFT74	Other/Unknown	no		IFT74
BBS10	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
SCLT1	Other/Unknown	no		SCLT1
BBS12	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
WDPCP	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, Frtz, WD40_repeat_dom_sf
CEP19	Other/Unknown	no		CEP19
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
BBS9	Other/Unknown	no		PTHB1, PHTB1_N_dom, PHTB1_GAE_dom
IFT172	Scaffold/PPI	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
LZTFL1	Other/Unknown	no		LZTFL1
MKKS	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
MKS1	Other/Unknown	no		C2_B9-type_dom
NPHP1	Scaffold/PPI	no		SH3_domain, NPHP1_SH3, SH3-like_dom_sf
BBS1	Other/Unknown	no		Quinoprotein_ADH-like_sf, BBS1, BBS1_N
BBS2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, Bardet-Biedl_syndrome_2_prot, BBS2_GAE_dom
BBS4	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt
BBS5	Other/Unknown	no		BBL5, PH-like_dom_sf, BBS5_PH
SCAPER	Transcription factor	no		Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type, SCAPER_N
TRIM32	Transcription factor	no		Znf_B-box, NHL_repeat, Znf_RING
BBIP1	Other/Unknown	no		BBIP10
USH2A	Antibody/Immunoglobulin	yes		Laminin_G, LE_dom, FN3_dom
RPGRIP1	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam
TSPOAP1	Antibody/Immunoglobulin	yes		SH3_domain, FN3_dom, Ig-like_fold
ASTN2	Complement	yes		MACPF, Astrotactin, FN3_sf
IFT57	Other/Unknown	no		Intra-flagellar_transport_57
WDR19	Transcription factor	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
IMPG2	Other/Unknown	no		SEA_dom, EGF, SEA_dom_sf
NPHP4	Other/Unknown	no		NPHP4, Ig_NPHP4_4th, Ig_NPHP4_3rd
TRAPPC3	Other/Unknown	no		TRAPP_component, Bet3, NO_sig/Golgi_transp_ligand-bd
COMT	Enzyme (other)	yes	2.1.1.6	SAM_O-MeTrfase, Catechol_O-MeTrfase_euk, SAM-dependent_MTases_sf
PHLDB1	Scaffold/PPI	no		FHA_dom, PH_domain, SMAD_FHA_dom_sf
ARL6IP6	Other/Unknown	no		ARL6IP6
AP5B1	Other/Unknown	no		AP5B1, AP5B1_N, AP5B1_middle
ADPGK	Kinase	yes	2.7.1.147	ADP_PFK/GK, Ribokinase-like
ZDHHC24	Other/Unknown	no		Palmitoyltrfase_DHHC, PFA4/ZDH16/20/ERF2-like
CCDC28B	Other/Unknown	no		CCDC28
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
IQCB1	Other/Unknown	no		IQ_motif_EF-hand-BS, ARM-type_fold, P-loop_NTPase
RPGRIP1L	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam
ABCB11	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
ALMS1	Other/Unknown	no		ALMS_motif, ALMS_repeat
GLI1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
GLI2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
ADGRG1	GPCR	yes		GPS, GPCR_2_secretin-like, GPR1/GPR3/GPR5
HTR2B	GPCR	yes		GPCR_Rhodpsn, 5HT2B_rcpt, 5HT_rcpt

Expression context

Cohort genes with no expression data: 0.

46 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)	54
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	14
bronchial epithelial cell	9
male germ line stem cell (sensu Vertebrata) in testis	7
ventricular zone	6
buccal mucosa cell	6
calcaneal tendon	5
endothelial cell	4
left ovary	4
sperm	4
oocyte	4
olfactory segment of nasal mucosa	4
epithelium of bronchus	3
monocyte	3
primordial germ cell in gonad	3
right adrenal gland cortex	3
stromal cell of endometrium	3
ganglionic eminence	3
adrenal tissue	2
leukocyte	2
secondary oocyte	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDCCAG8	134	ubiquitous	marker	corpus callosum, calcaneal tendon, thyroid gland
ARL6	228	ubiquitous	marker	oviduct epithelium, Brodmann (1909) area 23, endothelial cell
IFT27	251	ubiquitous	marker	right uterine tube, epithelium of bronchus, bronchial epithelial cell
BBS7	262	ubiquitous	marker	endothelial cell, calcaneal tendon, lateral nuclear group of thalamus
TTC8	247	ubiquitous	marker	left ovary, islet of Langerhans, adrenal tissue
IFT74	272	ubiquitous	marker	bronchial epithelial cell, caput epididymis, right uterine tube
BBS10	253	ubiquitous	yes	calcaneal tendon, endothelial cell, ventricular zone
SCLT1	217	ubiquitous	marker	buccal mucosa cell, monocyte, leukocyte
BBS12	204	ubiquitous	yes	primordial germ cell in gonad, sperm, bronchial epithelial cell
WDPCP	253	ubiquitous	marker	pancreatic ductal cell, kidney epithelium, mucosa of paranasal sinus
CEP19	214	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, blood
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
BBS9	279	ubiquitous	marker	oocyte, secondary oocyte, calcaneal tendon
IFT172	236	ubiquitous	marker	right uterine tube, bronchial epithelial cell, left testis
LZTFL1	282	ubiquitous	marker	bronchial epithelial cell, sperm, epithelium of bronchus
MKKS	277	ubiquitous	marker	middle temporal gyrus, endothelial cell, prefrontal cortex
MKS1	182	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, left ovary
NPHP1	193	ubiquitous	marker	right uterine tube, bronchial epithelial cell, olfactory segment of nasal mucosa
BBS1	134	ubiquitous	yes	right uterine tube, left ovary, ovary
BBS2	262	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, peripheral nervous system
BBS4	278	ubiquitous	marker	right uterine tube, oocyte, secondary oocyte
BBS5	140	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa
SCAPER	282	ubiquitous	marker	cortical plate, male germ line stem cell (sensu Vertebrata) in testis, sural nerve
TRIM32	252	ubiquitous	yes	stromal cell of endometrium, tibialis anterior, gastrocnemius
BBIP1	288	ubiquitous	marker	epithelium of nasopharynx, buccal mucosa cell, sperm
USH2A	30	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell
RPGRIP1	168	tissue_specific	marker	left testis, sperm, right testis
TSPOAP1	253	broad	marker	right uterine tube, right frontal lobe, granulocyte
ASTN2	236	ubiquitous	marker	buccal mucosa cell, trigeminal ganglion, dorsal root ganglion
IFT57	289	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 185.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
JAG1	4,405
GLI1	4,101
IQCB1	3,562
COMT	3,362
BBS10	3,224
GLI2	3,112
ALMS1	2,976
CEP290	2,778
MKKS	2,728
BBS4	2,544

Intra-cohort edges

A	B	Sources
ALMS1	BBS1	string_interaction
ALMS1	BBS10	string_interaction
ALMS1	BBS12	string_interaction
ALMS1	BBS2	string_interaction
ALMS1	BBS4	string_interaction
ALMS1	BBS5	string_interaction
ALMS1	BBS7	biogrid_interaction, intact, string_interaction
ALMS1	CEP290	string_interaction
ARL6	ARL6IP6	biogrid_interaction
ARL6	BBIP1	intact
ARL6	BBS1	intact, string_interaction
ARL6	BBS10	string_interaction
ARL6	BBS12	string_interaction
ARL6	BBS2	string_interaction
ARL6	BBS4	intact
ARL6	BBS5	string_interaction
ARL6	BBS7	intact, string_interaction
ARL6	BBS9	intact
ARL6	IFT27	string_interaction
ARL6	TTC8	string_interaction
ARL6	WDPCP	string_interaction
BBIP1	BBS4	intact
BBIP1	BBS5	biogrid_interaction, intact
BBIP1	BBS7	intact
BBIP1	IQCB1	intact
BBIP1	TTC8	biogrid_interaction, intact
BBS1	BBS10	string_interaction
BBS1	BBS12	intact, string_interaction
BBS1	BBS2	biogrid_interaction, intact, string_interaction
BBS1	BBS4	biogrid_interaction, intact, string_interaction
BBS1	BBS5	biogrid_interaction, intact, string_interaction
BBS1	BBS7	biogrid_interaction, intact, string_interaction
BBS1	BBS9	biogrid_interaction, intact
BBS1	CCDC28B	intact, string_interaction
BBS1	CEP290	string_interaction
BBS1	IQCB1	intact
BBS1	LZTFL1	biogrid_interaction, intact, string_interaction
BBS1	MKKS	string_interaction
BBS1	MKS1	string_interaction
BBS1	SDCCAG8	string_interaction
BBS1	TTC8	biogrid_interaction, intact, string_interaction
BBS1	WDPCP	string_interaction
BBS1	WDR19	string_interaction
BBS10	BBS12	intact, string_interaction
BBS10	BBS2	string_interaction
BBS10	BBS4	string_interaction
BBS10	BBS5	string_interaction
BBS10	BBS7	biogrid_interaction, intact, string_interaction
BBS10	BBS9	intact
BBS10	CCDC28B	string_interaction

Structural data

PDB: 25 · AlphaFold-only: 28 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COMT	P21964	12
HTR2B	P41595	12
ABCB11	O95342	8
JAG1	P78504	7
GLI1	P08151	5
WDR19	Q8NEZ3	4
TRAPPC3	O43617	4
ASTN2	O75129	3
BBS9	Q3SYG4	2
NPHP1	O15259	2
SCAPER	Q9BY12	2
TRIM32	Q13049	2
AP5B1	Q2VPB7	2
ARL6	Q9H0F7	1
WDPCP	O95876	1
IFT172	Q9UG01	1
BBS1	Q8NFJ9	1
BBS4	Q96RK4	1
BBS5	Q8N3I7	1
BBIP1	A8MTZ0	1
RPGRIP1	Q96KN7	1
TMEM67	Q5HYA8	1
RPGRIP1L	Q68CZ1	1
ADGRG1	Q9Y653	1
NPHP3	Q7Z494	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BBS7	Q8IWZ6	92.99
IFT27	Q9BW83	92.65
ADPGK	Q9BRR6	91.36
ZDHHC24	Q6UX98	89.76
BBS2	Q9BXC9	89.49
MKKS	Q9NPJ1	89.05
TTC8	Q8TAM2	84.48
LZTFL1	Q9NQ48	83.74
IQCB1	Q15051	83.05
CEP19	Q96LK0	82.85
SCLT1	Q96NL6	82.44
IFT74	Q96LB3	81.21
SDCCAG8	Q86SQ7	78.67
IFT57	Q9NWB7	76.92
MKS1	Q9NXB0	74.05
BBS12	Q6ZW61	73.92
NPHP4	O75161	72.44
BBS10	Q8TAM1	71.26
CCDC28B	Q9BUN5	71.15
CEP290	O15078	60.90
PHLDB1	Q86UU1	60.40
OTX1	P32242	58.01
TSPOAP1	O95153	57.91
ARL6IP6	Q8N6S5	56.77
IMPG2	Q9BZV3	54.28
GLI2	P10070	42.68
USH2A	O75445
ALMS1	Q8TCU4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 99. Enrichment computed across 54 evidence-associated genes (39 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 39 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
BBSome-mediated cargo-targeting to cilium	13	165.5×	1e-25	ARL6, BBS7, TTC8, BBS10, BBS12, BBS9, LZTFL1, MKKS (+5 more)
Cilium Assembly	18	50.2×	1e-25	SDCCAG8, ARL6, BBS7, BBS10, SCLT1, BBS12, CEP290, LZTFL1 (+10 more)
Organelle biogenesis and maintenance	18	30.5×	1e-21	SDCCAG8, ARL6, BBS7, BBS10, SCLT1, BBS12, CEP290, LZTFL1 (+10 more)
Cargo trafficking to the periciliary membrane	11	70.0×	5e-17	ARL6, BBS7, BBS10, BBS12, LZTFL1, MKKS, BBS1, BBS2 (+3 more)
Anchoring of the basal body to the plasma membrane	10	29.0×	2e-11	SDCCAG8, SCLT1, CEP290, MKS1, NPHP1, NPHP4, TMEM67, IQCB1 (+2 more)
Hedgehog ‘off’ state	7	32.0×	3e-08	IFT172, MKS1, IFT57, WDR19, RPGRIP1L, GLI1, GLI2
Intraflagellar transport	5	25.7×	2e-05	IFT27, IFT74, IFT172, IFT57, WDR19
GLI proteins bind promoters of Hh responsive genes to promote transcription	2	83.7×	0.003	GLI1, GLI2
Centrosome maturation	3	19.5×	0.005	SDCCAG8, CEP290, ALMS1
Loss of Nlp from mitotic centrosomes	3	12.2×	0.017	SDCCAG8, CEP290, ALMS1
Loss of proteins required for interphase microtubule organization from the centrosome	3	12.2×	0.017	SDCCAG8, CEP290, ALMS1
AURKA Activation by TPX2	3	11.7×	0.017	SDCCAG8, CEP290, ALMS1
Defective ABCB11 causes PFIC2 and BRIC2	1	292.8×	0.021	ABCB11
Recruitment of mitotic centrosome proteins and complexes	3	10.5×	0.021	SDCCAG8, CEP290, ALMS1
Regulation of PLK1 Activity at G2/M Transition	3	9.8×	0.021	SDCCAG8, CEP290, ALMS1
Mitotic G2-G2/M phases	3	9.8×	0.021	SDCCAG8, CEP290, ALMS1
G2/M Transition	3	9.8×	0.021	SDCCAG8, CEP290, ALMS1
Recruitment of NuMA to mitotic centrosomes	3	9.0×	0.025	SDCCAG8, CEP290, ALMS1
Enzymatic degradation of Dopamine by monoamine oxidase	1	146.4×	0.036	COMT
Enzymatic degradation of dopamine by COMT	1	97.6×	0.051	COMT
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	73.2×	0.064	JAG1
Trafficking of myristoylated proteins to the cilium	1	58.6×	0.073	NPHP3
RUNX2 regulates chondrocyte maturation	1	58.6×	0.073	GLI2
Mitotic Prometaphase	3	5.3×	0.076	SDCCAG8, CEP290, ALMS1
M Phase	3	5.1×	0.083	SDCCAG8, CEP290, ALMS1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	41.8×	0.090	JAG1
Hedgehog ‘on’ state	2	8.1×	0.092	GLI1, GLI2
Signaling by NOTCH1 HD Domain Mutants in Cancer	1	32.5×	0.107	JAG1
NOTCH4 Activation and Transmission of Signal to the Nucleus	1	26.6×	0.125	JAG1
Serotonin receptors	1	24.4×	0.125	HTR2B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 52 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	24	34.0×	7e-29	ARL6, IFT27, BBS7, TTC8, IFT74, SCLT1, WDPCP, CEP19 (+16 more)
non-motile cilium assembly	15	83.8×	2e-23	BBS7, TTC8, IFT74, BBS10, CEP290, IFT172, MKKS, MKS1 (+7 more)
photoreceptor cell maintenance	10	69.0×	2e-14	BBS10, BBS12, MKKS, BBS1, BBS2, BBS4, USH2A, NPHP4 (+2 more)
fat cell differentiation	10	34.9×	2e-11	ARL6, BBS7, TTC8, BBS12, BBS9, MKKS, BBS1, BBS2 (+2 more)
visual perception	12	18.3×	1e-10	ARL6, BBS7, BBS10, BBS9, MKKS, BBS1, BBS2, BBS4 (+4 more)
melanosome transport	6	88.4×	4e-09	ARL6, BBS7, MKKS, BBS2, BBS4, BBS5
heart looping	7	36.0×	6e-08	BBS7, IFT172, MKKS, BBS4, BBS5, IFT57, NPHP3
determination of left/right symmetry	7	34.4×	7e-08	ARL6, BBS7, IFT74, MKKS, MKS1, RPGRIP1L, NPHP3
regulation of cilium beat frequency involved in ciliary motility	4	144.0×	5e-07	MKKS, BBS1, BBS2, BBS4
smoothened signaling pathway	7	24.4×	6e-07	IFT27, BBS7, WDPCP, IFT172, IFT57, GLI1, GLI2
intraciliary transport	5	54.0×	1e-06	IFT27, BBS12, WDPCP, IFT172, IFT57
negative regulation of appetite by leptin-mediated signaling pathway	3	243.1×	4e-06	MKKS, BBS2, BBS4
striatum development	4	86.4×	4e-06	MKKS, BBS1, BBS2, BBS4
regulation of stress fiber assembly	4	76.2×	6e-06	TTC8, MKKS, BBS4, ALMS1
maintenance of animal organ identity	3	194.4×	9e-06	USH2A, IQCB1, NPHP3
intraciliary anterograde transport	4	68.2×	9e-06	IFT27, IFT74, IFT172, IFT57
cerebellar cortex morphogenesis	3	162.0×	2e-05	COMT, GLI1, GLI2
brain morphogenesis	4	56.4×	2e-05	MKKS, BBS1, BBS2, BBS4
regulation of smoothened signaling pathway	4	48.0×	3e-05	ARL6, MKS1, RPGRIP1L, GLI1
kidney development	6	16.2×	4e-05	IFT27, WDPCP, CEP290, RPGRIP1L, GLI2, NPHP3
protein transport	9	7.6×	5e-05	BBS7, TTC8, CEP290, BBS9, BBS4, BBS5, ASTN2, AP5B1 (+1 more)
retinal rod cell development	3	97.2×	7e-05	BBS4, RPGRIP1, RPGRIP1L
protein localization to cilium	4	30.9×	2e-04	ARL6, BBS9, BBS1, BBS4
pigment granule aggregation in cell center	2	324.1×	2e-04	BBS7, MKKS
convergent extension involved in gastrulation	2	324.1×	2e-04	MKKS, NPHP3
establishment of planar polarity	3	60.8×	3e-04	TTC8, WDPCP, RPGRIP1L
ventral midline development	2	216.1×	5e-04	GLI1, GLI2
sensory processing	2	216.1×	5e-04	TTC8, BBS4
inner ear receptor cell stereocilium organization	3	48.6×	5e-04	IFT27, TTC8, MKS1
negative regulation of keratinocyte proliferation	3	40.5×	8e-04	IFT74, IFT172, IFT57

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Setmelanotide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Metformin.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 4 · Undrugged: 50

Druggability breadth: 9 of 54 evidence-associated genes (17%) 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
COMT	OPICAPONE
ABCB11	TELMISARTAN
HTR2B	CETIRIZINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HTR2B	367	4
ABCB11	327	4
COMT	3	4
GLI1	1	1
SDCCAG8	0	0
ARL6	0	0
IFT27	0	0
BBS7	0	0
TTC8	0	0
IFT74	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OPICAPONE	4	COMT
TOLCAPONE	4	ABCB11, COMT
ENTACAPONE	4	ABCB11, COMT
TELMISARTAN	4	ABCB11, HTR2B
BEXAROTENE	4	ABCB11
PROGESTERONE	4	ABCB11, HTR2B
CLOTRIMAZOLE	4	ABCB11, HTR2B
LATANOPROST	4	ABCB11
SIMVASTATIN	4	ABCB11, HTR2B
METHYSERGIDE	4	ABCB11, HTR2B
VALSARTAN	4	ABCB11
BROMFENAC	4	ABCB11
CLOPIDOGREL BISULFATE	4	ABCB11
DIBUCAINE	4	ABCB11
VALRUBICIN	4	ABCB11
RIMONABANT	4	ABCB11, HTR2B
ARIPIPRAZOLE	4	ABCB11, HTR2B
DICYCLOMINE	4	ABCB11, HTR2B
ACITRETIN	4	ABCB11
TELITHROMYCIN	4	ABCB11
EZETIMIBE	4	ABCB11
SAQUINAVIR	4	ABCB11, HTR2B
CLOBETASOL PROPIONATE	4	ABCB11
AMPRENAVIR	4	ABCB11
MOMETASONE FUROATE	4	ABCB11
NORETHINDRONE	4	ABCB11
ATAZANAVIR	4	ABCB11
FEBUXOSTAT	4	ABCB11
PONATINIB	4	ABCB11, HTR2B
TETRABENAZINE	4	ABCB11, HTR2B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
HTR2B	1,090	Binding:786, Functional:249, ADMET:49, Toxicity:4, Unclassified:2
ABCB11	85	Binding:37, ADMET:31, Functional:13, Toxicity:4
COMT	55	Binding:47, ADMET:8
GLI1	44	Binding:44
GLI2	6	Binding:6
ADGRG1	3	Binding:3
TSPOAP1	1	Binding:1
PHLDB1	1	Binding:1
JAG1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
COMT	2.1.1.6	catechol O-methyltransferase
ADPGK	2.7.1.147	ADP-specific glucose/glucosamine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
HTR2B	1,090

Pharmacogenomics

Cohort genes with a PharmGKB record: 53; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
COMT	1

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)
OPICAPONE	4	COMT
TOLCAPONE	4	ABCB11, COMT
ENTACAPONE	4	ABCB11, COMT
TELMISARTAN	4	ABCB11, HTR2B
BEXAROTENE	4	ABCB11
PROGESTERONE	4	ABCB11, HTR2B
CLOTRIMAZOLE	4	ABCB11, HTR2B
LATANOPROST	4	ABCB11
SIMVASTATIN	4	ABCB11, HTR2B
METHYSERGIDE	4	ABCB11, HTR2B
VALSARTAN	4	ABCB11
BROMFENAC	4	ABCB11
CLOPIDOGREL BISULFATE	4	ABCB11
DIBUCAINE	4	ABCB11
VALRUBICIN	4	ABCB11
RIMONABANT	4	ABCB11, HTR2B
ARIPIPRAZOLE	4	ABCB11, HTR2B
DICYCLOMINE	4	ABCB11, HTR2B
ACITRETIN	4	ABCB11
TELITHROMYCIN	4	ABCB11
EZETIMIBE	4	ABCB11
SAQUINAVIR	4	ABCB11, HTR2B
CLOBETASOL PROPIONATE	4	ABCB11
AMPRENAVIR	4	ABCB11
MOMETASONE FUROATE	4	ABCB11
NORETHINDRONE	4	ABCB11
ATAZANAVIR	4	ABCB11
FEBUXOSTAT	4	ABCB11
PONATINIB	4	ABCB11, HTR2B
TETRABENAZINE	4	ABCB11, HTR2B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	COMT, ABCB11, HTR2B
B	Phased (≥1) drug, not yet approved	1	GLI1
C	Druggable family + PDB, no drug	2	ASTN2, ADGRG1
D	Druggable family + AlphaFold only, no drug	3	USH2A, TSPOAP1, ADPGK
E	Difficult family or no structure, no drug	45	SDCCAG8, ARL6, IFT27, BBS7, TTC8, IFT74, BBS10, SCLT1, BBS12, WDPCP (+35 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SDCCAG8	0	—
ARL6	0	—
IFT27	0	—
BBS7	0	—
TTC8	0	—
IFT74	0	—
BBS10	0	—
SCLT1	0	—
BBS12	0	—
WDPCP	0	—
CEP19	0	—
CEP290	0	—
BBS9	0	—
IFT172	0	—
LZTFL1	0	—
MKKS	0	—
MKS1	0	—
NPHP1	0	—
BBS1	0	—
BBS2	0	—
BBS4	0	—
BBS5	0	—
SCAPER	0	—
TRIM32	0	—
BBIP1	0	—
USH2A	0	—
RPGRIP1	0	—
TSPOAP1	1	—
ASTN2	0	—
IFT57	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 17.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	13
PHASE3	3
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT04966741	PHASE3	COMPLETED	Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
NCT05194124	PHASE3	COMPLETED	Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT02329210	Not specified	RECRUITING	Clinical Registry Investigating Bardet-Biedl Syndrome
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT04461444	Not specified	RECRUITING	COhort for Bardet-Bield Syndrome and Alström Syndrome for Translational Research Monocentric Interventional Study
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity
NCT06615011	Not specified	NOT_YET_RECRUITING	Bardet Beidle Syndrome in a Syrian Adolescent : a Rare Case Report
NCT00078091	Not specified	TERMINATED	Genetics and Clinical Characteristics of Bardet-Biedl Syndrome
NCT00213811	Not specified	COMPLETED	Bardet-Biedl Syndrome Study: Clinical and Genetic Epidemiology Study in Adults
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05183802	Not specified	APPROVED_FOR_MARKETING	An Expanded Access Protocol for Setmelanotide for Treatment of Bardet-Biedl Syndrome (BBS)
NCT05400278	Not specified	COMPLETED	Characterizing the Genotype and Phenotype in Adults With Bardet-Biedl Syndrome
NCT07602803	Not specified	COMPLETED	The Effect of GLP1 Agonists on Weight Loss in BBS Cohort in the UK

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SETMELANOTIDE	4	4
METFORMIN	4	1
CHEMBL4067491	0	4