Primary ciliary dyskinesia

Summary

Primary ciliary dyskinesia (MONDO:0016575) is a disease (an umbrella term covering 59 Mondo subtypes) caused by DNAH7 (GenCC Strong), with 75 cohort genes and 71 clinical trials. Top therapeutic interventions include thiamine ion, glycine, and ivacaftor.

At a glance

• Prevalence: 1-5 / 10 000 (Pakistan) [Orphanet-validated]
• Causal gene: DNAH7 (GenCC Strong)
• Umbrella term: 59 Mondo subtypes
• Cohort genes: 75
• ClinVar variants: 25,080
• Phenotypes (HPO): 47
• Clinical trials: 71

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	5	Europe	Validated
Point prevalence	1-5 / 10 000	44	Pakistan	Validated

Signs & symptoms

Clinical features (HPO)

47 HPO clinical features (Orphanet curated; top 47 by frequency):

HPO ID	Term	Frequency
HP:0000389	Chronic otitis media	Frequent (30-79%)
HP:0000403	Recurrent otitis media	Frequent (30-79%)
HP:0001742	Nasal congestion	Frequent (30-79%)
HP:0002257	Chronic rhinitis	Frequent (30-79%)
HP:0002643	Neonatal respiratory distress	Frequent (30-79%)
HP:0003251	Male infertility	Frequent (30-79%)
HP:0005425	Recurrent sinopulmonary infections	Frequent (30-79%)
HP:0011109	Chronic sinusitis	Frequent (30-79%)
HP:0011947	Respiratory tract infection	Frequent (30-79%)
HP:0012206	Abnormal sperm motility	Frequent (30-79%)
HP:0031245	Productive cough	Frequent (30-79%)
HP:0032016	Abnormal sputum	Frequent (30-79%)
HP:0100582	Nasal polyposis	Frequent (30-79%)
HP:0000119	Abnormality of the genitourinary system	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0000924	Abnormality of the skeletal system	Occasional (5-29%)
HP:0001217	Clubbing	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0001696	Situs inversus totalis	Occasional (5-29%)
HP:0002011	Morphological central nervous system abnormality	Occasional (5-29%)
HP:0002110	Bronchiectasis	Occasional (5-29%)
HP:0006536	Airway obstruction	Occasional (5-29%)
HP:0008222	Female infertility	Occasional (5-29%)
HP:0011274	Recurrent mycobacterial infections	Occasional (5-29%)
HP:0011617	Pulmonary situs ambiguus	Occasional (5-29%)
HP:0025177	Peribronchovascular interstitial thickening	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)
HP:0030828	Wheezing	Occasional (5-29%)
HP:0031456	Ectopic pregnancy	Occasional (5-29%)
HP:0032543	Lithoptysis	Occasional (5-29%)
HP:0100750	Atelectasis	Occasional (5-29%)
HP:0000238	Hydrocephalus	Very rare (<1-4%)
HP:0000510	Rod-cone dystrophy	Very rare (<1-4%)
HP:0001669	Transposition of the great arteries	Very rare (<1-4%)
HP:0001719	Double outlet right ventricle	Very rare (<1-4%)
HP:0001746	Asplenia	Very rare (<1-4%)
HP:0001748	Polysplenia	Very rare (<1-4%)
HP:0002119	Ventriculomegaly	Very rare (<1-4%)
HP:0002566	Intestinal malrotation	Very rare (<1-4%)
HP:0002878	Respiratory failure	Very rare (<1-4%)
HP:0005301	Persistent left superior vena cava	Very rare (<1-4%)
HP:0010772	Anomalous pulmonary venous return	Very rare (<1-4%)
HP:0011535	Abnormal atrial arrangement	Very rare (<1-4%)
HP:0011539	Atrial situs ambiguous	Very rare (<1-4%)
HP:0025576	Abnormal inferior vena cava morphology	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia
Mondo ID	MONDO:0016575
MeSH	D002925, D007619
OMIM	244400
Orphanet	244
DOID	DOID:0050144, DOID:9562
ICD-11	1713839459
NCIT	C84797
SNOMED CT	42402006, 86204009
UMLS	C0008780
MedGen	3467
GARD	0004484
MedDRA	10069713
NORD	1605
Is cancer (heuristic)	no

Also known as: bronchiectasis, chronic sinusitis and dextrocardia syndrome · ciliary dyskinesia primary · Dextrocardia bronchiectasis and sinusitis · Dextrocardia-bronchiectasis-sinusitis syndrome · ICS · Immotile cilia syndrome, Kartagener type · Kartagener syndrome · Kartagener’s syndrome · PCD · Primary ciliary dyskinesia and situs inversus · Primary ciliary dyskinesia, Kartagener type · Siewert syndrome

Data availability: 25,080 ClinVar variants · 53 GenCC gene-disease records · 12 cell lines.

Disease family

An umbrella term covering 59 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, long QT syndrome, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, Behcet disease, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Prader-Willi syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, polycystic ovary syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, 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 (59): ciliary discoordination due to random ciliary orientation, ciliary dyskinesia with transposition of ciliary microtubules, ciliary dyskinesia with defective radial spokes, ciliary dyskinesia with excessively long cilia, Stromme syndrome, primary ciliary dyskinesia 1, ciliary dyskinesia, primary, 36, X-linked, primary ciliary dyskinesia 2, primary ciliary dyskinesia 3, primary ciliary dyskinesia 4, primary ciliary dyskinesia 5, primary ciliary dyskinesia 6, primary ciliary dyskinesia 7, primary ciliary dyskinesia 8, primary ciliary dyskinesia 9, primary ciliary dyskinesia 10, primary ciliary dyskinesia 11, primary ciliary dyskinesia 12, primary ciliary dyskinesia 13, primary ciliary dyskinesia 14, primary ciliary dyskinesia 15, primary ciliary dyskinesia 16, primary ciliary dyskinesia 17, primary ciliary dyskinesia 18, primary ciliary dyskinesia 19, primary ciliary dyskinesia 20, primary ciliary dyskinesia 21, primary ciliary dyskinesia 22, primary ciliary dyskinesia 23, primary ciliary dyskinesia 24, primary ciliary dyskinesia 25, primary ciliary dyskinesia 26, primary ciliary dyskinesia 27, primary ciliary dyskinesia 28, primary ciliary dyskinesia 29, primary ciliary dyskinesia 30, primary ciliary dyskinesia 32, primary ciliary dyskinesia 33, primary ciliary dyskinesia 34, primary ciliary dyskinesia 35, ciliary dyskinesia, primary, 46, ciliary dyskinesia, primary, 47, and lissencephaly, ciliary dyskinesia, primary, 48, without situs inversus, ciliary dyskinesia, primary, 39, ciliary dyskinesia, primary, 40, ciliary dyskinesia, primary, 41, ciliary dyskinesia, primary, 42, ciliary dyskinesia, primary, 43, ciliary dyskinesia, primary, 44, ciliary dyskinesia, primary, 45, ciliary dyskinesia, primary, 37, ciliary dyskinesia, primary, 38, ciliary dyskinesia, primary, 54, ciliary dyskinesia, primary, 49, without situs inversus, ciliary dyskinesia, primary, 50, ciliary dyskinesia, primary, 51, ciliary dyskinesia, primary, 52, ciliary dyskinesia, primary, 53, CFAP46-related primary ciliary dyskinesia

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:

285 uncertain significance, 96 likely benign, 95 pathogenic, 58 conflicting classifications of pathogenicity, 26 likely pathogenic, 25 pathogenic/likely pathogenic, 14 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012311	NM_181426.2(CCDC39):c.2040_2043del (p.Cys680fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
1069445	NM_181426.2(CCDC39):c.1485dup (p.Ser496fs)	CCDC39	Pathogenic	criteria provided, single submitter
1070026	NM_181426.2(CCDC39):c.1964_1968del (p.Glu655fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070035	NM_181426.2(CCDC39):c.1674_1675dup (p.Ile559fs)	CCDC39	Pathogenic	criteria provided, single submitter
1073617	NM_181426.2(CCDC39):c.1208_1209insGGTGTGCTGTTGCGTGAACCTGGGAGGCGGAGCTTGCAGTGAGCCGAGATCGCGCCACTGCACTCCAGCCTGGGCGACAGAGCGAGACTCCGTCTCAAAAAAAAAAAAAAAAAGGTGTGCTGTT (p.Phe403fs)	CCDC39	Pathogenic	criteria provided, single submitter
1071463	NM_017950.4(CCDC40):c.1579del (p.Ala527fs)	CCDC40	Pathogenic	criteria provided, single submitter
1076172	NM_017950.4(CCDC40):c.3349G>T (p.Glu1117Ter)	CCDC40	Pathogenic	criteria provided, single submitter
1012795	NM_001277115.2(DNAH11):c.13418_13421dup (p.Tyr4476fs)	CDCA7L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069363	NM_178452.6(DNAAF1):c.922C>T (p.Gln308Ter)	DNAAF1	Pathogenic	criteria provided, single submitter
1076147	NC_000016.9:g.(?84182606)(84211452_?)del	DNAAF1	Pathogenic	criteria provided, single submitter
1073351	NM_001256715.2(DNAAF3):c.1195del (p.Ala399fs)	DNAAF3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073849	NM_001256715.2(DNAAF3):c.598_611del (p.Ser200fs)	DNAAF3	Pathogenic	criteria provided, single submitter
1030335	NM_001277115.2(DNAH11):c.3223C>T (p.Gln1075Ter)	DNAH11	Pathogenic	criteria provided, multiple submitters, no conflicts
1066542	NM_001277115.2(DNAH11):c.4254+5G>C	DNAH11	Pathogenic	criteria provided, single submitter
1067300	NM_001277115.2(DNAH11):c.2671A>G (p.Asn891Asp)	DNAH11	Pathogenic	criteria provided, single submitter
1068616	NM_001277115.2(DNAH11):c.1475_1593+946del	DNAH11	Pathogenic	criteria provided, single submitter
1068707	NM_001277115.2(DNAH11):c.11188C>T (p.Gln3730Ter)	DNAH11	Pathogenic	criteria provided, single submitter
1070658	NM_001277115.2(DNAH11):c.1320del (p.Lys440fs)	DNAH11	Pathogenic	criteria provided, single submitter
1073225	NM_001277115.2(DNAH11):c.5218C>T (p.Gln1740Ter)	DNAH11	Pathogenic	criteria provided, single submitter
1073724	NM_001277115.2(DNAH11):c.8076_8077del (p.Met2693fs)	DNAH11	Pathogenic	criteria provided, multiple submitters, no conflicts
1073850	NM_001277115.2(DNAH11):c.9478C>T (p.Arg3160Ter)	DNAH11	Pathogenic	criteria provided, single submitter
1074149	NM_001277115.2(DNAH11):c.13266_13272dup (p.Gly4425fs)	DNAH11	Pathogenic	criteria provided, single submitter
1076012	NM_001277115.2(DNAH11):c.5924+2T>A	DNAH11	Pathogenic	criteria provided, single submitter
1012297	NM_001369.3(DNAH5):c.1090del (p.Leu364fs)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1016659	NM_001369.3(DNAH5):c.6088T>G (p.Cys2030Gly)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066064	NM_001369.3(DNAH5):c.13774C>T (p.Arg4592Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066241	NM_001369.3(DNAH5):c.9897+1G>A	DNAH5	Pathogenic	criteria provided, single submitter
1067338	NM_001369.3(DNAH5):c.3835-2del	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069482	NC_000005.9:g.(?13931209)(13931363_?)del	DNAH5	Pathogenic	criteria provided, single submitter
1069562	NC_000005.9:g.(?13844936)(13845112_?)del	DNAH5	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 224 · Orphanet: 71 · 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
CCDC39	Definitive	Autosomal recessive	primary ciliary dyskinesia 14	4
CCDC40	Definitive	Autosomal recessive	primary ciliary dyskinesia 15	7
CCNO	Definitive	Autosomal recessive	primary ciliary dyskinesia 29	4
CFAP300	Definitive	Autosomal recessive	ciliary dyskinesia, primary, 38	3
DNAAF19	Definitive	Autosomal recessive	primary ciliary dyskinesia 17	4
DNAAF3	Definitive	Autosomal recessive	primary ciliary dyskinesia 2	5
DNAAF4	Definitive	Autosomal recessive	primary ciliary dyskinesia 25	4
DNAH11	Definitive	Autosomal recessive	primary ciliary dyskinesia 7	4
DNAH9	Definitive	Autosomal recessive	ciliary dyskinesia, primary, 40	7
DRC2	Definitive	Autosomal recessive	primary ciliary dyskinesia 27	3
DRC4	Definitive	Autosomal recessive	primary ciliary dyskinesia 33	5
HYDIN	Definitive	Autosomal recessive	primary ciliary dyskinesia 5	5
ODAD1	Definitive	Autosomal recessive	primary ciliary dyskinesia 20	3
ODAD2	Definitive	Autosomal recessive	primary ciliary dyskinesia 23	4
RSPH1	Definitive	Autosomal recessive	primary ciliary dyskinesia 24	5
RSPH3	Definitive	Autosomal recessive	primary ciliary dyskinesia 32	5
SPAG1	Definitive	Autosomal recessive	primary ciliary dyskinesia 28	4
CFAP298	Strong	Autosomal recessive	primary ciliary dyskinesia 26	2
DNAAF1	Strong	Autosomal recessive	primary ciliary dyskinesia 13	3
DNAAF2	Strong	Autosomal recessive	primary ciliary dyskinesia 10	4
DNAAF5	Strong	Autosomal recessive	primary ciliary dyskinesia 18	5
DNAAF6	Strong	X-linked	ciliary dyskinesia, primary, 36, X-linked	4
DNAH1	Strong	Autosomal recessive	ciliary dyskinesia, primary, 37	6
DNAH5	Strong	Autosomal recessive	primary ciliary dyskinesia 3	4
DNAH7	Strong	Autosomal recessive	primary ciliary dyskinesia	3
DNAI1	Strong	Autosomal recessive	primary ciliary dyskinesia 1	3
DNAI2	Strong	Autosomal recessive	primary ciliary dyskinesia 9	3
DNAJB13	Strong	Autosomal recessive	primary ciliary dyskinesia 34	5
DNAL1	Strong	Autosomal recessive	primary ciliary dyskinesia 16	4
DRC1	Strong	Autosomal recessive	primary ciliary dyskinesia 21	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPGR	Orphanet:1872	Cone rod dystrophy
RPGR	Orphanet:244	Primary ciliary dyskinesia
RPGR	Orphanet:247522	Primary ciliary dyskinesia-retinitis pigmentosa syndrome
RPGR	Orphanet:49382	Achromatopsia
RPGR	Orphanet:791	Retinitis pigmentosa
SPAG1	Orphanet:244	Primary ciliary dyskinesia
RSPH1	Orphanet:244	Primary ciliary dyskinesia
NME8	Orphanet:244	Primary ciliary dyskinesia
CCNO	Orphanet:244	Primary ciliary dyskinesia
NEK10	Orphanet:244	Primary ciliary dyskinesia
DNAH7	Orphanet:244	Primary ciliary dyskinesia
DNAI2	Orphanet:244	Primary ciliary dyskinesia
HYDIN	Orphanet:244	Primary ciliary dyskinesia
ZMYND10	Orphanet:244	Primary ciliary dyskinesia
AK7	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
DNAAF2	Orphanet:244	Primary ciliary dyskinesia
RSPH3	Orphanet:244	Primary ciliary dyskinesia
RSPH9	Orphanet:244	Primary ciliary dyskinesia
DNAAF4	Orphanet:244	Primary ciliary dyskinesia
RSPH4A	Orphanet:244	Primary ciliary dyskinesia
DNAL1	Orphanet:244	Primary ciliary dyskinesia
DRC1	Orphanet:244	Primary ciliary dyskinesia
DRC1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
GAS2L2	Orphanet:244	Primary ciliary dyskinesia
CCDC39	Orphanet:244	Primary ciliary dyskinesia
ODAD4	Orphanet:244	Primary ciliary dyskinesia
ODAD2	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:2750	Orofaciodigital syndrome type 1
OFD1	Orphanet:2754	Orofaciodigital syndrome type 6
OFD1	Orphanet:475	Isolated Joubert syndrome
OFD1	Orphanet:791	Retinitis pigmentosa
DNAAF5	Orphanet:244	Primary ciliary dyskinesia
CCDC40	Orphanet:244	Primary ciliary dyskinesia
SPEF2	Orphanet:244	Primary ciliary dyskinesia
SPEF2	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
ODAD1	Orphanet:244	Primary ciliary dyskinesia
CFAP300	Orphanet:244	Primary ciliary dyskinesia
ODAD3	Orphanet:244	Primary ciliary dyskinesia
DNAAF6	Orphanet:244	Primary ciliary dyskinesia
DNAH1	Orphanet:244	Primary ciliary dyskinesia
DNAH1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
DNAH11	Orphanet:244	Primary ciliary dyskinesia
DNAH5	Orphanet:244	Primary ciliary dyskinesia
DNAH9	Orphanet:101063	Situs inversus totalis
DNAH9	Orphanet:157769	Situs ambiguus
DNAH9	Orphanet:244	Primary ciliary dyskinesia
DNAI1	Orphanet:244	Primary ciliary dyskinesia
DRC2	Orphanet:244	Primary ciliary dyskinesia
DNAAF3	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

75 cohort genes, 71 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	gencc,clinvar
SPAG1	HGNC:11212	ENSG00000104450	Q07617	Sperm-associated antigen 1	gencc,clinvar
RSPH1	HGNC:12371	ENSG00000160188	Q8WYR4	Radial spoke head 1 homolog	gencc,clinvar
NME8	HGNC:16473	ENSG00000086288	Q8N427	Protein NME8	gencc,clinvar
CCNO	HGNC:18576	ENSG00000152669	P22674	Cyclin-O	gencc,clinvar
NEK10	HGNC:18592	ENSG00000163491	Q6ZWH5	Serine/threonine-protein kinase Nek10	gencc,clinvar
DNAH7	HGNC:18661	ENSG00000118997	Q8WXX0	Dynein axonemal heavy chain 7	gencc,clinvar
DNAI2	HGNC:18744	ENSG00000171595	Q9GZS0	Dynein axonemal intermediate chain 2	gencc,clinvar
HYDIN	HGNC:19368	ENSG00000157423	Q4G0P3	Hydrocephalus-inducing protein homolog	gencc,clinvar
ZMYND10	HGNC:19412	ENSG00000004838	O75800	Zinc finger MYND domain-containing protein 10	gencc,clinvar
AK7	HGNC:20091	ENSG00000140057	Q96M32	Adenylate kinase 7	gencc,clinvar
DNAAF2	HGNC:20188	ENSG00000165506	Q9NVR5	Protein kintoun	gencc,clinvar
RSPH3	HGNC:21054	ENSG00000130363	Q86UC2	Radial spoke head protein 3 homolog	gencc,clinvar
RSPH9	HGNC:21057	ENSG00000172426	Q9H1X1	Radial spoke head protein 9 homolog	gencc,clinvar
DNAAF4	HGNC:21493	ENSG00000256061	Q8WXU2	Dynein axonemal assembly factor 4	gencc,clinvar
RSPH4A	HGNC:21558	ENSG00000111834	Q5TD94	Radial spoke head protein 4 homolog A	gencc,clinvar
DNAL1	HGNC:23247	ENSG00000119661	Q4LDG9	Dynein axonemal light chain 1	gencc,clinvar
DRC1	HGNC:24245	ENSG00000157856	Q96MC2	Dynein regulatory complex protein 1	gencc,clinvar
GAS2L2	HGNC:24846	ENSG00000270765	Q8NHY3	GAS2-like protein 2	gencc,clinvar
CCDC39	HGNC:25244	ENSG00000284862	Q9UFE4	Coiled-coil domain-containing protein 39	gencc,clinvar
ODAD4	HGNC:25280	ENSG00000204815	Q96NG3	Outer dynein arm-docking complex subunit 4	gencc,clinvar
ODAD2	HGNC:25583	ENSG00000169126	Q5T2S8	Outer dynein arm-docking complex subunit 2	gencc,clinvar
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	gencc,clinvar
DNAAF5	HGNC:26013	ENSG00000164818	Q86Y56	Dynein axonemal assembly factor 5	gencc,clinvar
CCDC40	HGNC:26090	ENSG00000141519	Q4G0X9	Coiled-coil domain-containing protein 40	gencc,clinvar
SPEF2	HGNC:26293	ENSG00000152582	Q9C093	Sperm flagellar protein 2	gencc,clinvar
ODAD1	HGNC:26560	ENSG00000105479	Q96M63	Outer dynein arm-docking complex subunit 1	gencc,clinvar
CFAP300	HGNC:28188	ENSG00000137691	Q9BRQ4	Cilia- and flagella-associated protein 300	gencc,clinvar
ODAD3	HGNC:28303	ENSG00000198003	A5D8V7	Outer dynein arm-docking complex subunit 3	gencc,clinvar
DNAAF6	HGNC:28570	ENSG00000080572	Q9NQM4	Dynein axonemal assembly factor 6	gencc,clinvar
DNAH1	HGNC:2940	ENSG00000114841	Q9P2D7	Dynein axonemal heavy chain 1	gencc,clinvar
DNAH11	HGNC:2942	ENSG00000105877	Q96DT5	Dynein axonemal heavy chain 11	gencc,clinvar
DNAH5	HGNC:2950	ENSG00000039139	Q8TE73	Dynein axonemal heavy chain 5	gencc,clinvar
DNAH8	HGNC:2952	ENSG00000124721	Q96JB1	Dynein axonemal heavy chain 8	gencc,clinvar
DNAH9	HGNC:2953	ENSG00000007174	Q9NYC9	Dynein axonemal heavy chain 9	gencc,clinvar
DNAI1	HGNC:2954	ENSG00000122735	Q9UI46	Dynein axonemal intermediate chain 1	gencc,clinvar
DRC2	HGNC:29937	ENSG00000139537	Q8IXS2	Dynein regulatory complex subunit 2	gencc,clinvar
DNAAF3	HGNC:30492	ENSG00000167646	Q8N9W5	Dynein axonemal assembly factor 3	gencc,clinvar
DNAAF1	HGNC:30539	ENSG00000154099	Q8NEP3	Dynein axonemal assembly factor 1	gencc,clinvar
DNAJB13	HGNC:30718	ENSG00000187726	P59910	DnaJ homolog subfamily B member 13	gencc,clinvar
DNAAF19	HGNC:32700	ENSG00000167131	Q8IW40	Dynein axonemal assembly factor 19	gencc,clinvar
CFAP221	HGNC:33720	ENSG00000163075	Q4G0U5	Cilia- and flagella-associated protein 221	gencc,clinvar
MCIDAS	HGNC:40050	ENSG00000234602	D6RGH6	Multicilin	gencc,clinvar
DRC4	HGNC:4166	ENSG00000141013	O95995	Dynein regulatory complex subunit 4	gencc,clinvar
CFAP298	HGNC:1301	ENSG00000159079	P57076	Cilia- and flagella-associated protein 298	gencc
STK36	HGNC:17209	ENSG00000163482	Q9NRP7	Serine/threonine-protein kinase 36	gencc
TTC12	HGNC:23700	ENSG00000149292	Q9H892	Tetratricopeptide repeat protein 12	gencc
AKNA	HGNC:24108	ENSG00000106948	Q7Z591	Microtubule organization protein AKNA	gencc
LRRC56	HGNC:25430	ENSG00000161328	Q8IYG6	Leucine-rich repeat-containing protein 56	gencc
DNAH6	HGNC:2951	ENSG00000115423	Q9C0G6	Dynein axonemal heavy chain 6	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPGR	X-linked retinitis pigmentosa GTPase regulator	Acts as a guanine-nucleotide releasing factor (GEF) for RAB8A and RAB37 by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP.
SPAG1	Sperm-associated antigen 1	May play a role in the cytoplasmic assembly of the ciliary dynein arms.
RSPH1	Radial spoke head 1 homolog	Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
NME8	Protein NME8	Possesses an intrinsic kinase activity.
CCNO	Cyclin-O	Specifically required for generation of multiciliated cells, possibly by promoting a cell cycle state compatible with centriole amplification and maturation.
NEK10	Serine/threonine-protein kinase Nek10	Plays a role in the cellular response to UV irradiation.
DNAH7	Dynein axonemal heavy chain 7	Force generating protein that plays an important role in respiratory cilia and sperm flagella beating.
DNAI2	Dynein axonemal intermediate chain 2	Component of dynein, a family of motor proteins essential for movement along microtubules.
HYDIN	Hydrocephalus-inducing protein homolog	Required for ciliary motility.
ZMYND10	Zinc finger MYND domain-containing protein 10	Plays a role in axonemal structure organization and motility.
AK7	Adenylate kinase 7	Nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates.
DNAAF2	Protein kintoun	Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella.
RSPH3	Radial spoke head protein 3 homolog	Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
RSPH9	Radial spoke head protein 9 homolog	Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
DNAAF4	Dynein axonemal assembly factor 4	Axonemal dynein assembly factor required for ciliary motility.
RSPH4A	Radial spoke head protein 4 homolog A	Component of the axonemal radial spoke head which plays an important role in ciliary motility.
DNAL1	Dynein axonemal light chain 1	Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency.
DRC1	Dynein regulatory complex protein 1	Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.
GAS2L2	GAS2-like protein 2	Involved in the cross-linking of microtubules and microfilaments.
CCDC39	Coiled-coil domain-containing protein 39	Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella.
ODAD4	Outer dynein arm-docking complex subunit 4	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
ODAD2	Outer dynein arm-docking complex subunit 2	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.
DNAAF5	Dynein axonemal assembly factor 5	Cytoplasmic protein involved in the delivery of the dynein machinery to the motile cilium.
CCDC40	Coiled-coil domain-containing protein 40	Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella.
SPEF2	Sperm flagellar protein 2	Required for correct axoneme development in spermatozoa.
ODAD1	Outer dynein arm-docking complex subunit 1	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
CFAP300	Cilia- and flagella-associated protein 300	Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility.
ODAD3	Outer dynein arm-docking complex subunit 3	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
DNAAF6	Dynein axonemal assembly factor 6	Plays a role in cytoplasmic pre-assembly of axonemal dynein.
DNAH1	Dynein axonemal heavy chain 1	Force generating protein of cilia required for sperm flagellum motility.
DNAH11	Dynein axonemal heavy chain 11	Force generating protein required for cilia beating in respiratory epithelia.
DNAH5	Dynein axonemal heavy chain 5	Force generating protein of respiratory cilia.
DNAH8	Dynein axonemal heavy chain 8	Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum.
DNAH9	Dynein axonemal heavy chain 9	Force generating protein required for cilia beating in respiratory epithelia.
DNAI1	Dynein axonemal intermediate chain 1	Component of dynein, a family of motor proteins essential for movement along microtubules.
DRC2	Dynein regulatory complex subunit 2	Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.
DNAAF3	Dynein axonemal assembly factor 3	Required for the assembly of axonemal inner and outer dynein arms.
DNAAF1	Dynein axonemal assembly factor 1	Cilium-specific protein required for the stability of the ciliary architecture.
DNAJB13	DnaJ homolog subfamily B member 13	Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
DNAAF19	Dynein axonemal assembly factor 19	Dynein-attachment factor required for cilia motility.
CFAP221	Cilia- and flagella-associated protein 221	May play a role in cilium morphogenesis and ciliary function.
MCIDAS	Multicilin	Transcription regulator specifically required for multiciliate cell differentiation.
DRC4	Dynein regulatory complex subunit 4	Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.
CFAP298	Cilia- and flagella-associated protein 298	Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly.
STK36	Serine/threonine-protein kinase 36	Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors.
TTC12	Tetratricopeptide repeat protein 12	Cytoplasmic protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella.
AKNA	Microtubule organization protein AKNA	Centrosomal protein that plays a key role in cell delamination by regulating microtubule organization.
LRRC56	Leucine-rich repeat-containing protein 56	Required for the assembly of dynein arms.
DNAH6	Dynein axonemal heavy chain 6	Force generating protein of respiratory cilia.

Protein-family classification

Druggable: 9 · Difficult: 8 · Unknown: 58 · Druggable fraction: 0.12

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	58	1.4×	6e-04
Complement	1	3.6×	0.857
Scaffold/PPI	5	1.1×	0.996
Antibody/Immunoglobulin	2	0.8×	0.996
Kinase	2	0.7×	0.996
Enzyme (other)	4	0.6×	0.996
Transcription factor	3	0.3×	0.996

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
SPAG1	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, RPAP3-like_C
RSPH1	Other/Unknown	no		MORN
NME8	Other/Unknown	no		Thioredoxin_domain, Thioredoxin_CS, NDK-like_dom
CCNO	Enzyme (other)	yes	3.2.2.27	Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
NEK10	Kinase	yes		Prot_kinase_dom, Tyr_kinase_AS, Kinase-like_dom_sf
DNAH7	Other/Unknown	no		EF_hand_dom, AAA+_ATPase, Dhc_D6_P-loop
DNAI2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
HYDIN	Antibody/Immunoglobulin	yes		Ig-like_fold, P-loop_NTPase, Hydin-like
ZMYND10	Transcription factor	no		Znf_MYND, UCP037948_Znf-MYND, ZMYND10
AK7	Enzyme (other)	yes	2.7.4.3	Adenylat/UMP-CMP_kin, Dpy-30_motif, P-loop_NTPase
DNAAF2	Other/Unknown	no		PIH1_N, Kintoun, PIH1D1/2/3_CS-like
RSPH3	Other/Unknown	no		Radial_spoke_3
RSPH9	Other/Unknown	no		RSP9
DNAAF4	Other/Unknown	no		CS_dom, HSP20-like_chaperone, TPR-like_helical_dom_sf
RSPH4A	Other/Unknown	no		Radial_spoke
DNAL1	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_4, LRR_dom_sf
DRC1	Other/Unknown	no		DRC1_C, DRC1/2_N, DRC1/DRC2
GAS2L2	Other/Unknown	no		CH_dom, GAR_dom, GAR_dom_sf
CCDC39	Other/Unknown	no		CCDC39
ODAD4	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, ODAD4
ODAD2	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold
OFD1	Other/Unknown	no		LisH, OFD1
DNAAF5	Other/Unknown	no		HEAT, ARM-like, ARM-type_fold
CCDC40	Other/Unknown	no		CCDC40
SPEF2	Other/Unknown	no		CH_dom, CH_2, EF-hand-dom_pair
ODAD1	Other/Unknown	no		ODAD1_CC, ODA-DC/CCD
CFAP300	Other/Unknown	no		CFAP300
ODAD3	Other/Unknown	no		ODAD3
DNAAF6	Other/Unknown	no		DNAAF6, PIH1D1/2/3_CS-like
DNAH1	Other/Unknown	no		Dhc_D6_P-loop, Dhc_linker, Dhc_D4
DNAH11	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DNAH5	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DNAH8	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DNAH9	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DNAI1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
DRC2	Other/Unknown	no		DRC1/2_N, DRC1/DRC2
DNAAF3	Other/Unknown	no		DUF4470, DNAAF3_C, DNAAF3
DNAAF1	Other/Unknown	no		Leu-rich_rpt, LRR_dom_sf, Cilia_flagella_integrity
DNAJB13	Other/Unknown	no		DnaJ_domain, DnaJ_C, HSP40/DnaJ_pept-bd
DNAAF19	Other/Unknown	no		RPAP3-like_C, Dynein_attach_N, CC103
CFAP221	Antibody/Immunoglobulin	yes		Ig-like_fold, CFAP221
MCIDAS	Other/Unknown	no		Geminin/Multicilin
DRC4	Other/Unknown	no		GAS8_dom, GAS8
CFAP298	Other/Unknown	no		CFAP298
STK36	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TTC12	Other/Unknown	no		ARM-like, TPR-like_helical_dom_sf, ARM-type_fold
AKNA	Other/Unknown	no		AKNA_dom, AKNA_Centrosome-Trans_reg
LRRC56	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_4, LRR_dom_sf
DNAH6	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dhc_linker

Expression context

Cohort genes with no expression data: 0.

68 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	1
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	36
bronchial epithelial cell	34
bronchus	15
male germ line stem cell (sensu Vertebrata) in testis	11
epithelium of bronchus	11
left testis	11
sperm	10
olfactory segment of nasal mucosa	8
right testis	5
primordial germ cell in gonad	4
secondary oocyte	4
oviduct epithelium	4
sural nerve	4
oocyte	3
granulocyte	2
mucosa of paranasal sinus	2
apex of heart	2
testis	2
adenohypophysis	2
lower lobe of lung	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPGR	281	ubiquitous	marker	sperm, bronchial epithelial cell, right uterine tube
SPAG1	249	ubiquitous	marker	bronchial epithelial cell, mucosa of sigmoid colon, palpebral conjunctiva
RSPH1	200	broad	marker	bronchial epithelial cell, bronchus, right uterine tube
NME8	155		yes	granulocyte, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
CCNO	172	broad	marker	oocyte, secondary oocyte, epithelium of bronchus
NEK10	178	broad	marker	olfactory segment of nasal mucosa, right uterine tube, left testis
DNAH7	212	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
DNAI2	115	tissue_specific	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
HYDIN	136	broad	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, corpus callosum
ZMYND10	175	broad	marker	right uterine tube, left testis, right testis
AK7	168	broad	marker	bronchial epithelial cell, bronchus, right uterine tube
DNAAF2	273	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, oocyte
RSPH3	243	ubiquitous	marker	bronchial epithelial cell, oviduct epithelium, bronchus
RSPH9	167	broad	marker	bronchial epithelial cell, bronchus, mucosa of paranasal sinus
DNAAF4	188	ubiquitous	marker	bronchial epithelial cell, bronchus, secondary oocyte
RSPH4A	164	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, mucosa of paranasal sinus
DNAL1	224	ubiquitous	marker	buccal mucosa cell, oviduct epithelium, left testis
DRC1	141	broad	marker	right uterine tube, bronchial epithelial cell, bronchus
GAS2L2	103	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, bronchial epithelial cell
CCDC39	132	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, endometrium
ODAD4	196	ubiquitous	marker	right uterine tube, bronchial epithelial cell, sperm
ODAD2	173	broad	marker	bronchial epithelial cell, right uterine tube, sperm
OFD1	288	ubiquitous	marker	sperm, bronchial epithelial cell, cervix squamous epithelium
DNAAF5	280	ubiquitous	marker	bronchial epithelial cell, secondary oocyte, epithelium of bronchus
CCDC40	184	ubiquitous	marker	right uterine tube, bronchial epithelial cell, sural nerve
SPEF2	181	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
ODAD1	174	broad	marker	oviduct epithelium, right uterine tube, bronchial epithelial cell
CFAP300	181	ubiquitous	marker	bronchial epithelial cell, bronchus, sperm
ODAD3	177	broad	marker	bronchial epithelial cell, bronchus, right uterine tube
DNAAF6	72	tissue_specific	marker	bronchial epithelial cell, bronchus, sperm

Protein interactions among cohort

Intra-cohort edges: 368.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL6	9,239
NME8	8,310
CYBB	4,117
AK7	3,054
OFD1	2,878
PRKAR1B	2,865
RSPH3	2,848
OTC	2,513
DNAJB13	2,412
ODAD2	2,251

Intra-cohort edges

A	B	Sources
AK7	DNAH6	string_interaction
CCDC39	CCDC40	string_interaction
CCDC39	CCNO	string_interaction
CCDC39	CFAP57	string_interaction
CCDC39	DNAAF1	string_interaction
CCDC39	DNAAF11	string_interaction
CCDC39	DNAAF19	string_interaction
CCDC39	DNAAF3	string_interaction
CCDC39	DNAH1	string_interaction
CCDC39	DNAH11	string_interaction
CCDC39	DNAH5	string_interaction
CCDC39	DNAH7	string_interaction
CCDC39	DNAH8	string_interaction
CCDC39	DNAH9	string_interaction
CCDC39	DNAI1	string_interaction
CCDC39	DNAI2	string_interaction
CCDC39	DRC1	string_interaction
CCDC39	DRC2	string_interaction
CCDC39	DRC4	string_interaction
CCDC39	HYDIN	string_interaction
CCDC39	MCIDAS	string_interaction
CCDC39	ODAD1	string_interaction
CCDC39	ODAD2	string_interaction
CCDC39	ODAD3	string_interaction
CCDC39	RSPH1	string_interaction
CCDC39	RSPH3	string_interaction
CCDC39	RSPH4A	string_interaction
CCDC39	RSPH9	string_interaction
CCDC39	ZMYND10	string_interaction
CCDC40	CCNO	string_interaction
CCDC40	CFAP57	string_interaction
CCDC40	DNAAF1	string_interaction
CCDC40	DNAAF11	string_interaction
CCDC40	DNAAF19	string_interaction
CCDC40	DNAAF3	string_interaction
CCDC40	DNAH1	string_interaction
CCDC40	DNAH11	string_interaction
CCDC40	DNAH5	string_interaction
CCDC40	DNAH7	string_interaction
CCDC40	DNAH9	string_interaction
CCDC40	DNAI1	string_interaction
CCDC40	DNAI2	string_interaction
CCDC40	DRC1	string_interaction
CCDC40	DRC2	string_interaction
CCDC40	DRC4	string_interaction
CCDC40	HYDIN	string_interaction
CCDC40	MCIDAS	string_interaction
CCDC40	ODAD1	string_interaction
CCDC40	ODAD2	string_interaction
CCDC40	ODAD3	string_interaction

Structural data

PDB: 35 · AlphaFold-only: 36 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL6	P05231	17
CYBB	P04839	6
SPAG1	Q07617	4
OTC	P00480	4
RPGR	Q92834	3
PRKAR1B	P31321	3
DNAH7	Q8WXX0	2
HYDIN	Q4G0P3	2
ZMYND10	O75800	2
DNAH1	Q9P2D7	2
CDCA7L	Q96GN5	2
RSPH1	Q8WYR4	1
DNAI2	Q9GZS0	1
RSPH3	Q86UC2	1
RSPH9	Q9H1X1	1
RSPH4A	Q5TD94	1
DNAL1	Q4LDG9	1
DRC1	Q96MC2	1
CCDC39	Q9UFE4	1
ODAD4	Q96NG3	1
ODAD2	Q5T2S8	1
CCDC40	Q4G0X9	1
ODAD1	Q96M63	1
ODAD3	A5D8V7	1
DNAH5	Q8TE73	1
DNAH9	Q9NYC9	1
DNAI1	Q9UI46	1
DRC2	Q8IXS2	1
DNAJB13	P59910	1
MCIDAS	D6RGH6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AGPAT3	Q9NRZ7	94.63
CFAP300	Q9BRQ4	94.21
DNAAF5	Q86Y56	92.80
TTC12	Q9H892	90.27
CFAP298	P57076	86.54
SRPX	P78539	85.37
DNAAF4	Q8WXU2	84.00
AK7	Q96M32	82.35
CACNA2D2	Q9NY47	81.48
STK36	Q9NRP7	81.22
DNAAF3	Q8N9W5	81.06
DNAAF19	Q8IW40	80.42
NME8	Q8N427	79.81
CCNO	P22674	79.06
DNAAF11	Q86X45	74.44
DNAAF6	Q9NQM4	73.41
SPEF2	Q9C093	71.30
KRTAP12-2	P59991	70.96
NEK10	Q6ZWH5	70.23
GOLGA3	Q08378	68.76
OFD1	O75665	68.41
DNAAF2	Q9NVR5	65.57
TAF1C	Q15572	64.79
FAM219A	Q8IW50	63.93
CFAP221	Q4G0U5	63.53
TTC14	Q96N46	62.21
FAM162B	Q5T6X4	61.89
DNAAF1	Q8NEP3	61.56
FOXJ1	Q92949	59.44
GAS2L2	Q8NHY3	56.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 111. Enrichment computed across 76 evidence-associated genes (14 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 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
OTC leader sequence variants cause OTC deficiency	1	815.7×	0.050	OTC
OTC main chain variants cause OTC deficiency	1	815.7×	0.050	OTC
ADORA2B mediated anti-inflammatory cytokines production	2	36.2×	0.050	IL6, PRKAR1B
Regulation of insulin secretion	2	31.4×	0.050	CACNA2D2, PRKAR1B
Hedgehog ‘off’ state	2	25.5×	0.051	OFD1, PRKAR1B
Integration of energy metabolism	2	25.1×	0.051	CACNA2D2, PRKAR1B
Cross-presentation of particulate exogenous antigens (phagosomes)	1	102.0×	0.104	CYBB
MAPK1 (ERK2) activation	1	81.6×	0.104	IL6
CD163 mediating an anti-inflammatory response	1	81.6×	0.104	IL6
MAPK3 (ERK1) activation	1	74.2×	0.104	IL6
Interleukin-6 signaling	1	68.0×	0.104	IL6
Presynaptic depolarization and calcium channel opening	1	68.0×	0.104	CACNA2D2
CREB1 phosphorylation through the activation of Adenylate Cyclase	1	62.8×	0.104	PRKAR1B
Urea cycle	1	62.8×	0.104	OTC
Phase 2 - plateau phase	1	54.4×	0.104	CACNA2D2
PKA activation in glucagon signalling	1	48.0×	0.104	PRKAR1B
PKA activation	1	45.3×	0.104	PRKAR1B
Activation of SMO	1	45.3×	0.104	DRC4
PKA-mediated phosphorylation of CREB	1	40.8×	0.104	PRKAR1B
DARPP-32 events	1	34.0×	0.104	PRKAR1B
RHO GTPases Activate NADPH Oxidases	1	32.6×	0.104	CYBB
Adrenaline,noradrenaline inhibits insulin secretion	1	28.1×	0.104	CACNA2D2
Anti-inflammatory response favouring Leishmania parasite infection	1	28.1×	0.104	PRKAR1B
Leishmania parasite growth and survival	1	28.1×	0.104	PRKAR1B
Calmodulin induced events	1	27.2×	0.104	PRKAR1B
CaM pathway	1	27.2×	0.104	PRKAR1B
Ca-dependent events	1	26.3×	0.104	PRKAR1B
Tight junction interactions	1	26.3×	0.104	CLDN2
Aquaporin-mediated transport	1	26.3×	0.104	PRKAR1B
Interconversion of nucleotide di- and triphosphates	1	25.5×	0.104	AK7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 64 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
outer dynein arm assembly	18	206.1×	1e-38	DNAI2, ZMYND10, DNAAF2, DNAAF4, DNAL1, ODAD4, ODAD2, DNAAF5 (+10 more)
cilium movement	21	128.6×	1e-38	DNAH7, DNAI2, HYDIN, ZMYND10, RSPH9, DNAAF4, RSPH4A, CCDC39 (+13 more)
axonemal dynein complex assembly	13	213.9×	5e-28	SPAG1, DNAAF2, DRC1, CCDC39, CCDC40, DNAAF6, DRC2, DNAAF3 (+5 more)
inner dynein arm assembly	12	166.3×	1e-23	DNAH7, ZMYND10, DNAAF2, DNAAF4, CCDC39, DNAAF5, CCDC40, DNAAF6 (+4 more)
epithelial cilium movement involved in extracellular fluid movement	12	143.6×	1e-22	DNAAF2, DNAAF4, RSPH4A, CCDC40, SPEF2, DNAH1, DNAH5, DNAI1 (+4 more)
epithelial cilium movement involved in determination of left/right asymmetry	9	182.3×	3e-18	CCDC39, ODAD4, OFD1, CCDC40, ODAD3, DNAH11, DNAAF1, DNAAF19 (+1 more)
determination of left/right symmetry	13	51.9×	7e-18	DNAI2, DNAAF4, DRC1, ODAD2, ODAD3, DNAH11, DNAH5, DNAI1 (+5 more)
motile cilium assembly	10	90.8×	2e-16	ZMYND10, RSPH9, CCDC39, CCDC40, DNAAF3, DNAAF1, CFAP221, MCIDAS (+2 more)
cilium movement involved in cell motility	9	94.8×	6e-15	DNAH7, RSPH9, RSPH4A, DNAH11, DNAH5, DNAH8, DNAH9, DRC4 (+1 more)
axoneme assembly	9	76.5×	5e-14	RSPH1, RSPH9, RSPH4A, OFD1, CCDC40, DNAAF1, DRC4, STK36 (+1 more)
cerebrospinal fluid circulation	8	110.9×	6e-14	CCDC39, ODAD4, ODAD3, DNAH9, DNAAF3, CFAP221, DNAAF11, DAW1
cilium-dependent cell motility	7	153.6×	2e-13	DNAH7, DNAAF2, DRC1, CCDC39, DNAH1, DNAH8, DRC2
cilium assembly	14	16.1×	3e-12	RPGR, NME8, CCNO, DNAI2, OFD1, DNAH5, DRC2, DNAAF1 (+6 more)
flagellated sperm motility	11	20.1×	1e-10	NME8, CCDC39, CCDC40, ODAD3, DNAAF6, DNAH1, DNAH11, DNAH5 (+3 more)
regulation of cilium beat frequency	5	164.6×	8e-10	CCDC39, ODAD2, CCDC40, DNAH11, DNAAF1
establishment of localization in cell	9	22.6×	4e-09	DNAAF2, DNAAF4, RSPH4A, CCDC39, DNAH5, DNAH9, CFAP221, DRC4 (+1 more)
mucociliary clearance	5	101.3×	2e-08	NEK10, DRC1, ODAD4, DNAH9, CFAP221
determination of digestive tract left/right asymmetry	4	175.5×	5e-08	CCDC39, CCDC40, DNAAF1, DNAAF19
heart development	9	11.1×	2e-06	DNAAF4, DRC1, ODAD4, ODAD2, DNAH5, DNAI1, DNAAF3, DAW1 (+1 more)
regulation of cilium movement	3	197.5×	3e-06	DRC1, DRC2, CFAP298
determination of pancreatic left/right asymmetry	3	158.0×	7e-06	CCDC39, CCDC40, DNAAF1
protein localization to motile cilium	3	158.0×	7e-06	ODAD4, DNAH11, DNAAF11
protein localization to cilium	5	31.4×	7e-06	ZMYND10, CCDC39, CCDC40, DRC4, DNAAF11
determination of liver left/right asymmetry	3	131.7×	1e-05	CCDC39, CCDC40, DNAAF1
axonemal central apparatus assembly	3	131.7×	1e-05	HYDIN, RSPH9, DNAJB13
seminiferous tubule development	4	47.9×	2e-05	CCNO, ODAD3, DNAAF3, MCIDAS
single fertilization	6	17.2×	2e-05	SPAG1, CCNO, DRC1, ODAD3, MCIDAS, CFAP57
lung development	5	15.5×	2e-04	CCDC39, ODAD4, CCDC40, DNAAF3, DNAAF1
radial spoke assembly	2	175.5×	5e-04	RSPH9, RSPH4A
heart looping	4	16.7×	0.001	CCDC39, CCDC40, DNAAF1, DNAAF19

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

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

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 70

Druggability breadth: 10 of 76 evidence-associated genes (13%) 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
STK36	FEDRATINIB
CACNA2D2	NIMODIPINE
CYBB	NALOXONE
IL6	PREDNISOLONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STK36	19	4
CYBB	4	4
CACNA2D2	3	4
IL6	3	4
NEK10	1	3
RPGR	0	0
SPAG1	0	0
RSPH1	0	0
NME8	0	0
CCNO	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	STK36
SORAFENIB	4	STK36
NERATINIB	4	STK36
BOSUTINIB	4	STK36
PAZOPANIB	4	STK36
DASATINIB	4	STK36
ERLOTINIB	4	STK36
GEFITINIB	4	STK36
NIMODIPINE	4	CACNA2D2
TACRINE	4	CACNA2D2
PREGABALIN	4	CACNA2D2
NALOXONE	4	CYBB
PREDNISOLONE	4	IL6
LEROCICLIB	3	NEK10
CANERTINIB	3	STK36
LESTAURTINIB	3	STK36
EBSELEN	3	CYBB
FORETINIB	2	STK36
DEFOSBARASERTIB	2	STK36
R-406	2	STK36
RAF-265	2	STK36
PELITINIB	2	STK36
SETANAXIB	2	CYBB
ISUZINAXIB	2	CYBB
FOSDAGROCORAT	2	IL6
R-1487	1	STK36
BMS-387032	1	STK36
GSK-690693	1	STK36
AST-487	1	STK36
BI 653048	1	IL6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
STK36	77	Binding:77
CYBB	56	Binding:54, Unclassified:1, Functional:1
NEK10	40	Binding:40
CCNO	22	Binding:22
CACNA2D2	17	Binding:17
IL6	16	Binding:16
OTC	3	Binding:3
GOLGA3	1	Binding:1
TTC14	1	Binding:1
PRKAR1B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CCNO	3.2.2.27	uracil-DNA glycosylase
AK7	2.7.4.3	adenylate kinase
AGPAT3	2.3.1.51	1-acylglycerol-3-phosphate O-acyltransferase
OTC	2.1.3.3	ornithine carbamoyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 71; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	STK36
SORAFENIB	4	STK36
NERATINIB	4	STK36
BOSUTINIB	4	STK36
PAZOPANIB	4	STK36
DASATINIB	4	STK36
ERLOTINIB	4	STK36
GEFITINIB	4	STK36
NIMODIPINE	4	CACNA2D2
TACRINE	4	CACNA2D2
PREGABALIN	4	CACNA2D2
NALOXONE	4	CYBB
PREDNISOLONE	4	IL6
LEROCICLIB	3	NEK10
CANERTINIB	3	STK36
LESTAURTINIB	3	STK36
EBSELEN	3	CYBB
FORETINIB	2	STK36
DEFOSBARASERTIB	2	STK36
R-406	2	STK36
RAF-265	2	STK36
PELITINIB	2	STK36
SETANAXIB	2	CYBB
ISUZINAXIB	2	CYBB
FOSDAGROCORAT	2	IL6
R-1487	1	STK36
BMS-387032	1	STK36
GSK-690693	1	STK36
AST-487	1	STK36
BI 653048	1	IL6

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	STK36, CACNA2D2, CYBB, IL6
B	Phased (≥1) drug, not yet approved	1	NEK10
C	Druggable family + PDB, no drug	2	HYDIN, OTC
D	Druggable family + AlphaFold only, no drug	5	CCNO, AK7, CFAP221, SRPX, AGPAT3
E	Difficult family or no structure, no drug	63	RPGR, SPAG1, RSPH1, NME8, DNAH7, DNAI2, ZMYND10, DNAAF2, RSPH3, RSPH9 (+53 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SRPX	0	CYBB
RPGR	0	—
SPAG1	0	—
RSPH1	0	—
NME8	0	—
CCNO	22	—
DNAH7	0	—
DNAI2	0	—
HYDIN	0	—
ZMYND10	0	—
AK7	0	—
DNAAF2	0	—
RSPH3	0	—
RSPH9	0	—
DNAAF4	0	—
RSPH4A	0	—
DNAL1	0	—
DRC1	0	—
GAS2L2	0	—
CCDC39	0	—
ODAD4	0	—
ODAD2	0	—
OFD1	0	—
DNAAF5	0	—
CCDC40	0	—
SPEF2	0	—
ODAD1	0	—
CFAP300	0	—
ODAD3	0	—
DNAAF6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 71.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	65
PHASE1	3
PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT05737485	PHASE1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	PHASE1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT04901715	EARLY_PHASE1	COMPLETED	Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
NCT00807482	Not specified	RECRUITING	Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
NCT01929356	Not specified	RECRUITING	Chest Physiotherapy and Lung Function in Primary Ciliary Dyskinesia
NCT02419365	Not specified	RECRUITING	International Primary Ciliary Dyskinesia (PCD) Registry
NCT02704455	Not specified	NOT_YET_RECRUITING	Registry Study on Primary Ciliary Dyskinesia in Chinese Children
NCT03517865	Not specified	ACTIVE_NOT_RECRUITING	International Primary Ciliary Dyskinesia Cohort
NCT03606200	Not specified	RECRUITING	Swiss Primary Ciliary Dyskinesia Registry
NCT03704207	Not specified	RECRUITING	Utility of PCD Diagnostics to Improve Clinical Care
NCT04602481	Not specified	RECRUITING	Living With Primary Ciliary Dyskinesia (Living With PCD)
NCT04611516	Not specified	RECRUITING	The Ear-Nose-Throat (ENT) Prospective International Cohort of PCD Patients (EPIC-PCD)
NCT05287022	Not specified	RECRUITING	Use of Nasal Nitric Oxide Testing in Improving Primary Ciliary Dyskinesia Clinical Care
NCT05889013	Not specified	RECRUITING	Utility of PCD Diagnostics to Improve Clinical Care
NCT05951478	Not specified	RECRUITING	DCP (RaDiCo Cohort) (RaDiCo-DCP)
NCT06172374	Not specified	ACTIVE_NOT_RECRUITING	A Study Providing Genetic Testing to Find Those Who May Have Primary Ciliary Dyskinesia for Potential Clinical Trials
NCT06959251	Not specified	RECRUITING	Glycine and Magnesium+Thiamine for the Treatment of Primary Ciliary Dyskinesia
NCT07029594	Not specified	RECRUITING	Thermal Spa Treatment and Improvement of Primary Ciliary Dyskinesia
NCT07274631	Not specified	RECRUITING	A Cohort for Inflammatory Respiratory Diseases: From Phenotyping to Personalised Medicine
NCT07288827	Not specified	RECRUITING	Examining Bronchial Hyperresponsiveness in Primary Ciliary Dyskinesia
NCT07357558	Not specified	RECRUITING	A Qualitative Study Investigating the Lived Experiences and Impact of Reproductive Issues in Adults With Primary Ciliary Dyskinesia
NCT07376187	Not specified	NOT_YET_RECRUITING	Digital Physiotherapy for Pediatric Chronic Suppurative Lung Diseases
NCT07417267	Not specified	ENROLLING_BY_INVITATION	Clean Air for Rare MUcociliary Clearance dIsorders
NCT07531277	Not specified	NOT_YET_RECRUITING	Developing Resource Interventions for Healthcare Professionals and Patients to Improve Knowledge About Fertility in Primary Ciliary Dyskinesia
NCT00005650	Not specified	COMPLETED	Genetic Study of Patients With Primary Ciliary Dyskinesia
NCT00323167	Not specified	COMPLETED	Rare Genetic Disorders of the Breathing Airways
NCT00368446	Not specified	COMPLETED	Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
NCT00450918	Not specified	COMPLETED	Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT00686309	Not specified	UNKNOWN	Comparison of On-line and Off-line Measurements of Exhaled Nitric Oxide (NO)
NCT00722878	Not specified	COMPLETED	Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease
NCT00739817	Not specified	UNKNOWN	Screening for Primary Ciliary Dyskinesia Using Nasal Nitric Oxide
NCT00783887	Not specified	COMPLETED	Diagnosis of Primary Ciliary Dyskinesia
NCT01070914	Not specified	UNKNOWN	Early Detection and Characterization of Primary Ciliary Dyskinesia
NCT01155115	Not specified	COMPLETED	Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
NCT01246258	Not specified	COMPLETED	Otolith Function in Patients With Primary Ciliary Dyskinesia
NCT02389049	Not specified	COMPLETED	Genetics of Primary Ciliary Dyskinesia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
THIAMINE ION	4	2
GLYCINE	4	1
IVACAFTOR	4	1
METHACHOLINE	4	1
SODIUM CHLORIDE	4	1
IDREVLORIDE	2	1