Prader-Willi syndrome

Summary

Prader-Willi syndrome (MONDO:0008300) is a disease (an umbrella term covering 5 Mondo subtypes) caused by SNRPN (GenCC Definitive), with 11 cohort genes and 135 clinical trials. Top therapeutic interventions include pitolisant, octreotide, and cannabidiol.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: SNRPN (GenCC Definitive)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 11
• ClinVar variants: 53
• Phenotypes (HPO): 90
• Clinical trials: 135

Clinical features

Epidemiology

Prevalence records

16 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Prevalence at birth	1-9 / 100 000	3.1	Europe	Validated
Point prevalence	1-9 / 100 000	1.3	Belgium	Validated
Point prevalence	1-9 / 100 000	1.9	United Kingdom	Validated
Point prevalence	1-9 / 100 000		Japan	Validated
Point prevalence	1-9 / 100 000		Australia	Validated
Point prevalence	1-9 / 100 000		United States	Validated
Point prevalence	1-9 / 1 000 000	0.229	China	Validated
Prevalence at birth	1-9 / 100 000	3.7	Belgium	Validated
Prevalence at birth	1-9 / 100 000	3.4	United Kingdom	Validated
Prevalence at birth	1-9 / 100 000	6.6	Japan	Validated
Prevalence at birth	1-9 / 100 000	4	Australia	Validated
Prevalence at birth	1-9 / 100 000	6.2	United States	Validated
Prevalence at birth	1-9 / 100 000	4.76	France	Validated
Point prevalence	1-9 / 100 000		Worldwide	Not yet validated
Prevalence at birth	1-9 / 100 000		Worldwide	Not yet validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000739	Anxiety	Very frequent (80-99%)
HP:0000789	Infertility	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001270	Motor delay	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0002015	Dysphagia	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0008872	Feeding difficulties in infancy	Very frequent (80-99%)
HP:0025160	Abnormal temper tantrums	Very frequent (80-99%)
HP:0002494	Abnormal rapid eye movement sleep	Frequent (30-79%)
HP:0002578	Gastroparesis	Frequent (30-79%)
HP:0002591	Polyphagia	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002659	Increased susceptibility to fractures	Frequent (30-79%)
HP:0002870	Obstructive sleep apnea	Frequent (30-79%)
HP:0003241	External genital hypoplasia	Frequent (30-79%)
HP:0005599	Hypopigmentation of hair	Frequent (30-79%)
HP:0005616	Accelerated skeletal maturation	Frequent (30-79%)
HP:0006297	Enamel hypoplasia	Frequent (30-79%)
HP:0006889	Intellectual disability, borderline	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0008734	Decreased testicular size	Frequent (30-79%)
HP:0010536	Central sleep apnea	Frequent (30-79%)
HP:0010829	Impaired temperature sensition	Frequent (30-79%)
HP:0012506	Small pituitary gland	Frequent (30-79%)
HP:0012650	Perisylvian polymicrogyria	Frequent (30-79%)
HP:0012743	Abdominal obesity	Frequent (30-79%)
HP:0030339	Decreased circulating gonadotropin level	Frequent (30-79%)
HP:0034323	Reduced circulating growth hormone concentration	Frequent (30-79%)
HP:0200055	Small hand	Frequent (30-79%)
HP:0410263	Brain imaging abnormality	Frequent (30-79%)
HP:0000046	Small scrotum	Frequent (30-79%)
HP:0000059	Hypoplastic labia majora	Frequent (30-79%)
HP:0000060	Clitoral hypoplasia	Frequent (30-79%)
HP:0000064	Hypoplastic labia minora	Frequent (30-79%)
HP:0000135	Hypogonadism	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000540	Hypermetropia	Frequent (30-79%)
HP:0000545	Myopia	Frequent (30-79%)
HP:0000678	Dental crowding	Frequent (30-79%)
HP:0000704	Periodontitis	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0000786	Primary amenorrhea	Frequent (30-79%)
HP:0000823	Delayed puberty	Frequent (30-79%)
HP:0000824	Decreased response to growth hormone stimulation test	Frequent (30-79%)
HP:0000938	Osteopenia	Frequent (30-79%)
HP:0000939	Osteoporosis	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Prader-Willi syndrome
Mondo ID	MONDO:0008300
MeSH	D011218
OMIM	176270
Orphanet	739
DOID	DOID:11983
ICD-10-CM	Q87.11
ICD-11	393773440
NCIT	C75463
SNOMED CT	89392001
UMLS	C0032897
MedGen	46057
GARD	0005575
MedDRA	10036476
NORD	1602
Is cancer (heuristic)	no

Also known as: obesity, muscular hypotonia, intellectual disability, short stature, hypogonadotropic hypogonadism, and small hands and feet · obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet · Prader-Labhart-Willi syndrome · Prader-Willi syndrome · Prader-Willi-Labhart syndrome · PWS · Willi-Prader syndrome

Data availability: 53 ClinVar variants · 2 GenCC gene-disease records · 98 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Prader-Willi syndrome

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, long QT syndrome, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, Behcet disease, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, polycystic ovary syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, Takayasu arteritis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, hypotrichosis-deafness syndrome, thalidomide embryopathy, trisomy X, trisomy 13, trisomy 18, umbilical cord ulceration-intestinal atresia syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, infantile spasms, Wolfram syndrome, epidermal nevus syndrome, digital anomalies-intellectual disability-short stature syndrome, intellectual disability-obesity-brain malformations-facial dysmorphism syndrome, Erdheim-Chester disease, Stevens-Johnson syndrome, CADDS, finger hyperphalangy - toe anomalies - severe pectus excavatum syndrome, ataxia - telangiectasia variant, growth retardation-mild developmental delay-chronic hepatitis syndrome, primary microcephaly-mild intellectual disability-young-onset diabetes syndrome, ferro-cerebro-cutaneous syndrome, dystonia-aphonia syndrome, microcephaly-complex motor and sensory axonal neuropathy syndrome, X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, intrauterine growth restriction-short stature-early adult-onset diabetes syndrome, pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa, familial chylomicronemia syndrome, caudal regression-sirenomelia spectrum, visceral heterotaxy, Holmes-Adie syndrome, microcephalic primordial dwarfism due to RTTN deficiency, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, Kallmann syndrome, Caroli syndrome, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability, microlissencephaly-micromelia syndrome, branchiootic syndrome, Plummer-Vinson syndrome, Cushing syndrome, McCune-Albright syndrome, Meckel syndrome, SUNCT syndrome, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, congenital myasthenic syndrome, Loeys-Dietz syndrome, Alport syndrome, schisis association, Tolosa-Hunt syndrome, iridocorneal endothelial syndrome, Noonan syndrome, short fifth metacarpals-insulin resistance syndrome, progressive supranuclear palsy, benign exophthalmos syndrome, Sandifer syndrome, global developmental delay-osteopenia-ectodermal defect syndrome, tubular renal disease-cardiomyopathy syndrome, angioosteohypotrophic syndrome, 6q terminal deletion syndrome, Axenfeld-Rieger syndrome, peroxisome biogenesis disorder, ectodermal dysplasia syndrome, Seckel syndrome, Sotos syndrome, Stickler syndrome, pelvis syndrome, Susac syndrome, ischio-vertebral syndrome, BRESEK syndrome, Turner syndrome, 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 (5): Schaaf-Yang syndrome, Prader-Willi syndrome due to translocation, Prader-Willi syndrome due to imprinting mutation, Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15, Prader-Willi syndrome due to paternal 15q11q13 deletion

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

53 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 12 pathogenic, 6 benign/likely benign, 3 conflicting classifications of pathogenicity, 2 likely benign, 2 pathogenic/likely pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
625711	GRCh37/hg19 15q11.2-13.3(chr15:20848750-32925141)	APBA2	Pathogenic	criteria provided, single submitter
1703557	GRCh37/hg19 15q11.2-13.1(chr15:22770421-28635058)	ATP10A	Pathogenic	no assertion criteria provided
375417	Single allele	ATP10A	Pathogenic	criteria provided, single submitter
625716	GRCh37/hg19 15q11.2-13.1(chr15:23615768-28561671)	ATP10A	Pathogenic	criteria provided, single submitter
625717	GRCh37/hg19 15q11.2-13.1(chr15:23683783-28530182)	ATP10A	Pathogenic	criteria provided, single submitter
625718	GRCh37/hg19 15q11.2-13.1(chr15:23810184-28525505)	ATP10A	Pathogenic	criteria provided, single submitter
3374711	GRCh37/hg19 15q11.2(chr15:22698522-25199682)x1	CYFIP1	Pathogenic	criteria provided, single submitter
625713	GRCh37/hg19 15q11.2-13.1(chr15:22770994-29050198)	GABRA5	Pathogenic	criteria provided, single submitter
803061	NM_004667.6(HERC2):c.4126C>T (p.Arg1376Ter)	HERC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
931703	NM_004667.6(HERC2):c.11701-1G>A	HERC2	Pathogenic	criteria provided, single submitter
1685934	NM_019066.5(MAGEL2):c.2894G>A (p.Trp965Ter)	MAGEL2	Pathogenic	criteria provided, single submitter
1685935	NM_019066.5(MAGEL2):c.2099dup (p.Val701fs)	MAGEL2	Pathogenic	criteria provided, single submitter
208684	NM_019066.5(MAGEL2):c.1912C>T (p.Gln638Ter)	MAGEL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1697252	NM_022807.5(SNRPN):c.-390-9497_-390-228del	SNHG14	Pathogenic	no assertion criteria provided
930278	NM_019066.5(MAGEL2):c.2945_2946del (p.Leu981_Ser982insTer)	MAGEL2	Likely pathogenic	criteria provided, single submitter
3779852	NM_005664.4(MKRN3):c.137C>A (p.Ser46Ter)	MKRN3	Likely pathogenic	criteria provided, single submitter
1284465	NM_019066.5(MAGEL2):c.1991C>T (p.Pro664Leu)	MAGEL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
435798	NM_019066.5(MAGEL2):c.959C>A (p.Ala320Asp)	MAGEL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
435800	NM_019066.5(MAGEL2):c.385A>G (p.Met129Val)	MAGEL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029884	NM_004667.6(HERC2):c.7069+3G>A	HERC2	Uncertain significance	criteria provided, single submitter
392903	NM_004667.6(HERC2):c.13612G>A (p.Val4538Met)	HERC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
450670	NM_004667.6(HERC2):c.5374A>G (p.Met1792Val)	HERC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
452637	NM_004667.6(HERC2):c.8399G>A (p.Arg2800His)	HERC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
930448	NM_004667.6(HERC2):c.8012C>G (p.Ala2671Gly)	HERC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
930652	NM_004667.6(HERC2):c.8598C>G (p.Ile2866Met)	HERC2	Uncertain significance	criteria provided, single submitter
931262	NM_004667.6(HERC2):c.10424C>T (p.Ser3475Phe)	HERC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
931263	NM_004667.6(HERC2):c.5351G>A (p.Arg1784His)	HERC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028140	NM_019066.5(MAGEL2):c.1640C>T (p.Pro547Leu)	MAGEL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028141	NM_019066.5(MAGEL2):c.1972G>A (p.Ala658Thr)	MAGEL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1325548	NM_019066.5(MAGEL2):c.220G>A (p.Ala74Thr)	MAGEL2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 21 · 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
SNRPN	Definitive	Autosomal dominant	Prader-Willi syndrome
NDN	Limited	Autosomal dominant	Prader-Willi syndrome

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDN	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
NDN	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
NDN	Orphanet:177910	Prader-Willi syndrome due to imprinting mutation
NDN	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
SNRPN	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
SNRPN	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
SNRPN	Orphanet:177907	Prader-Willi syndrome due to translocation
SNRPN	Orphanet:177910	Prader-Willi syndrome due to imprinting mutation
SNRPN	Orphanet:411515	Angelman syndrome due to imprinting defect in 15q11-q13
SNRPN	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
ATP10A	Orphanet:411515	Angelman syndrome due to imprinting defect in 15q11-q13
GABRA5	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
HERC2	Orphanet:329195	Developmental delay with autism spectrum disorder and gait instability
MAGEL2	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
MAGEL2	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
MAGEL2	Orphanet:177910	Prader-Willi syndrome due to imprinting mutation
MAGEL2	Orphanet:398069	Schaaf-Yang syndrome
MAGEL2	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
MAGEL2	Orphanet:994	Fetal akinesia deformation sequence
MKRN3	Orphanet:650077	Genetic central precocious puberty in female
MKRN3	Orphanet:650097	Genetic central precocious puberty in male

Cohort genes → proteins

11 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	11

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NDN	HGNC:7675	ENSG00000182636	Q99608	Necdin	gencc,clinvar
SNRPN	HGNC:11164	ENSG00000128739	P63162	Small nuclear ribonucleoprotein-associated protein N	gencc
NPAP1	HGNC:1190	ENSG00000185823	Q9NZP6	Nuclear pore-associated protein 1	clinvar
ATP10A	HGNC:13542	ENSG00000206190	O60312	Phospholipid-transporting ATPase VA	clinvar
CYFIP1	HGNC:13759	ENSG00000273749	Q7L576	Cytoplasmic FMR1-interacting protein 1	clinvar
SNHG14	HGNC:37462	ENSG00000224078		small nucleolar RNA host gene 14	clinvar
GABRA5	HGNC:4079	ENSG00000186297	P31644	Gamma-aminobutyric acid receptor subunit alpha-5	clinvar
HERC2	HGNC:4868	ENSG00000128731	O95714	E3 ubiquitin-protein ligase HERC2	clinvar
APBA2	HGNC:579	ENSG00000034053	Q99767	Amyloid-beta A4 precursor protein-binding family A member 2	clinvar
MAGEL2	HGNC:6814	ENSG00000254585	Q9UJ55	MAGE-like protein 2	clinvar
MKRN3	HGNC:7114	ENSG00000179455	Q13064	E3 ubiquitin-protein ligase makorin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDN	Necdin	Growth suppressor that facilitates the entry of the cell into cell cycle arrest.
SNRPN	Small nuclear ribonucleoprotein-associated protein N	May be involved in tissue-specific alternative RNA processing events.
NPAP1	Nuclear pore-associated protein 1	May be involved in spermatogenesis.
ATP10A	Phospholipid-transporting ATPase VA	Catalytic component of P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of phosphatidylcholine (PC) from the outer to the inner leaflet of the plasma membrane.
CYFIP1	Cytoplasmic FMR1-interacting protein 1	Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression.
GABRA5	Gamma-aminobutyric acid receptor subunit alpha-5	Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
HERC2	E3 ubiquitin-protein ligase HERC2	E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes.
APBA2	Amyloid-beta A4 precursor protein-binding family A member 2	Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery.
MAGEL2	MAGE-like protein 2	Probably enhances ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases, possibly through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex.
MKRN3	E3 ubiquitin-protein ligase makorin-3	E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.

Protein-family classification

Druggable: 0 · Difficult: 4 · Unknown: 7 · Druggable fraction: 0.0

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
Transcription factor	3	2.2×	0.418
Scaffold/PPI	1	1.6×	0.481
Other/Unknown	7	1.1×	0.481

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NDN	Other/Unknown	no		MHD_dom, MAGE, MAGE_WH1
SNRPN	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, snRNP-assoc_SmB/SmN
NPAP1	Other/Unknown	no		Nucleoporin
ATP10A	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
CYFIP1	Other/Unknown	no		Cytoplasmic_FMR1-int, CYRIA/CYRIB_Rac1-bd
SNHG14	Other/Unknown	no
GABRA5	Other/Unknown	no		GABAAa_rcpt, GABBAa5_rcpt, GABAA/Glycine_rcpt
HERC2	Transcription factor	no		Reg_chr_condens, Znf_ZZ, HECT_dom
APBA2	Scaffold/PPI	no		PDZ, PTB/PI_dom, PH-like_dom_sf
MAGEL2	Other/Unknown	no		MHD_dom, MAGE, MAGE_WH1
MKRN3	Transcription factor	no		Znf_CCCH, Znf_RING, Znf_RING/FYVE/PHD

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	11
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	3
adrenal tissue	2
endothelial cell	2
prefrontal cortex	2
superior frontal gyrus	2
right hemisphere of cerebellum	2
tendon of biceps brachii	1
primary visual cortex	1
ileal mucosa	1
right testis	1
descending thoracic aorta	1
thoracic aorta	1
epithelium of esophagus	1
esophagus squamous epithelium	1
germinal epithelium of ovary	1
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
pons	1
Brodmann (1909) area 10	1
nucleus accumbens	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDN	282	ubiquitous	marker	endothelial cell, adrenal tissue, tendon of biceps brachii
SNRPN	134	broad	marker	superior frontal gyrus, prefrontal cortex, primary visual cortex
NPAP1	40	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, ileal mucosa, right testis
ATP10A	229	broad	marker	endothelial cell, descending thoracic aorta, thoracic aorta
CYFIP1	295	ubiquitous	marker	esophagus squamous epithelium, germinal epithelium of ovary, epithelium of esophagus
SNHG14	283	broad	marker	lateral nuclear group of thalamus, Brodmann (1909) area 23, pons
GABRA5	141	broad	marker	nucleus accumbens, prefrontal cortex, Brodmann (1909) area 10
HERC2	146		marker	sural nerve, right hemisphere of cerebellum, cerebellar cortex
APBA2	131	ubiquitous	marker	superior frontal gyrus, right hemisphere of cerebellum, cerebellum
MAGEL2	132	broad	marker	adrenal tissue, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
MKRN3	163	broad	marker	ganglionic eminence, cortical plate, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 14.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HERC2	2,843
APBA2	2,193
NDN	2,190
CYFIP1	2,156
GABRA5	1,907
MKRN3	1,494
ATP10A	1,016
MAGEL2	908
SNRPN	373
NPAP1	300

Intra-cohort edges

A	B	Sources
APBA2	HERC2	biogrid_interaction, intact
ATP10A	GABRA5	string_interaction
ATP10A	MAGEL2	string_interaction
ATP10A	MKRN3	string_interaction
ATP10A	NDN	string_interaction
ATP10A	NPAP1	string_interaction
GABRA5	MAGEL2	string_interaction
GABRA5	MKRN3	string_interaction
MAGEL2	MKRN3	string_interaction
MAGEL2	NDN	biogrid_interaction
MAGEL2	NPAP1	string_interaction
MKRN3	NDN	string_interaction
MKRN3	NPAP1	string_interaction
NDN	NPAP1	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 5 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GABRA5	P31644	23
HERC2	O95714	15
CYFIP1	Q7L576	5
SNRPN	P63162	2
MKRN3	Q13064	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP10A	O60312	71.30
NDN	Q99608	68.01
APBA2	Q99767	59.74
MAGEL2	Q9UJ55	44.28
NPAP1	Q9NZP6	36.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 33. Enrichment computed across 11 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RHO GTPases Activate WASPs and WAVEs	1	45.3×	0.115	CYFIP1
GABA receptor activation	1	45.3×	0.115	GABRA5
Protein-protein interactions at synapses	1	37.9×	0.115	APBA2
Ion transport by P-type ATPases	1	29.7×	0.115	ATP10A
Neurexins and neuroligins	1	28.1×	0.115	APBA2
FCGR3A-mediated phagocytosis	1	26.7×	0.115	CYFIP1
Regulation of actin dynamics for phagocytic cup formation	1	26.3×	0.115	CYFIP1
Nonhomologous End-Joining (NHEJ)	1	24.0×	0.115	HERC2
RHOG GTPase cycle	1	21.2×	0.115	CYFIP1
SUMOylation of DNA damage response and repair proteins	1	20.9×	0.115	HERC2
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	20.9×	0.115	HERC2
VEGFA-VEGFR2 Pathway	1	19.9×	0.115	CYFIP1
RAC2 GTPase cycle	1	18.1×	0.115	CYFIP1
G2/M DNA damage checkpoint	1	17.2×	0.115	HERC2
RAC3 GTPase cycle	1	17.0×	0.115	CYFIP1
Processing of DNA double-strand break ends	1	16.3×	0.115	HERC2
mRNA Splicing	1	15.7×	0.115	SNRPN
CHD1 and CHD2 subfamily	1	15.5×	0.115	SNRPN
Interleukin-4 and Interleukin-13 signaling	1	14.7×	0.115	NDN
Ion channel transport	1	13.7×	0.117	ATP10A
mRNA Polyadenylation	1	12.6×	0.121	SNRPN
Processing of Capped Intron-Containing Pre-mRNA	1	11.7×	0.123	SNRPN
Signaling by Interleukins	1	9.2×	0.149	NDN
RAC1 GTPase cycle	1	8.7×	0.150	CYFIP1
mRNA Splicing - Major Pathway	1	7.8×	0.160	SNRPN
Dengue Virus-Host Interactions	1	6.5×	0.181	SNRPN
Neuronal System	1	6.3×	0.181	APBA2
Metabolism of RNA	1	6.0×	0.182	SNRPN
Cytokine Signaling in Immune system	1	5.8×	0.182	NDN
Antigen processing: Ubiquitination & Proteasome degradation	1	5.3×	0.191	HERC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
axon extension	2	99.1×	0.012	NDN, CYFIP1
multicellular organismal-level homeostasis	1	561.7×	0.030	NDN
regulation of translation at postsynapse, modulating synaptic transmission	1	561.7×	0.030	CYFIP1
positive regulation of membrane tubulation	1	561.7×	0.030	ATP10A
positive regulation of actin nucleation	1	337.0×	0.030	MAGEL2
positive regulation of neurotrophin TRK receptor signaling pathway	1	337.0×	0.030	CYFIP1
regulation of cell shape	2	24.6×	0.030	ATP10A, CYFIP1
inner ear receptor cell development	1	240.7×	0.033	GABRA5
regulation of modification of postsynaptic actin cytoskeleton	1	240.7×	0.033	CYFIP1
positive regulation of Arp2/3 complex-mediated actin nucleation	1	210.7×	0.034	CYFIP1
dendrite extension	1	168.5×	0.038	CYFIP1
glial cell migration	1	140.4×	0.040	NDN
ruffle organization	1	129.6×	0.040	CYFIP1
Arp2/3 complex-mediated actin nucleation	1	105.3×	0.040	MAGEL2
neurotrophin TRK receptor signaling pathway	1	105.3×	0.040	NDN
genomic imprinting	1	99.1×	0.040	NDN
respiratory system process	1	93.6×	0.040	NDN
RNA export from nucleus	1	93.6×	0.040	NPAP1
axonal fasciculation	1	93.6×	0.040	NDN
innervation	1	88.7×	0.040	GABRA5
phospholipid translocation	1	62.4×	0.048	ATP10A
inhibitory synapse assembly	1	62.4×	0.048	GABRA5
positive regulation of lamellipodium assembly	1	60.2×	0.048	CYFIP1
regulation of actin filament polymerization	1	58.1×	0.048	CYFIP1
Rac protein signal transduction	1	56.2×	0.048	CYFIP1
gamma-aminobutyric acid signaling pathway	1	54.4×	0.048	GABRA5
synaptic transmission, GABAergic	1	49.6×	0.048	GABRA5
associative learning	1	48.1×	0.048	GABRA5
cochlea development	1	46.8×	0.048	GABRA5
presynaptic modulation of chemical synaptic transmission	1	45.5×	0.048	APBA2

Therapeutics

Drugs indicated for this disease

1 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Somatropin	Approved (phase 4)
Beloranib	Phase 3 (in late-stage trials)
Carbetocin	Phase 3 (in late-stage trials)
Rimonabant	Phase 3 (in late-stage trials)
Topiramate	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cannabidiol, Metoprolol, Oxytocin, Pitolisant, Setmelanotide, Sodium Chloride, Ubidecarenone.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 10

Druggability breadth: 3 of 11 evidence-associated genes (27%) 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
GABRA5	ENZALUTAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GABRA5	27	4
NDN	0	0
SNRPN	0	0
NPAP1	0	0
ATP10A	0	0
CYFIP1	0	0
SNHG14	0	0
HERC2	0	0
APBA2	0	0
MAGEL2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ENZALUTAMIDE	4	GABRA5
DIAZEPAM	4	GABRA5
LIOTHYRONINE	4	GABRA5
GANAXOLONE	4	GABRA5
BREXANOLONE	4	GABRA5
APALUTAMIDE	4	GABRA5
FLUMAZENIL	4	GABRA5
CLONAZEPAM	4	GABRA5
FLUNITRAZEPAM	4	GABRA5
CHLORDIAZEPOXIDE	4	GABRA5
TRIAZOLAM	4	GABRA5
PROPOFOL	4	GABRA5
ALPRAZOLAM	4	GABRA5
DELORAZEPAM	2	GABRA5
FLAVONE	2	GABRA5
PROGABIDE	2	GABRA5
ABECARNIL	2	GABRA5
BAICALEIN	2	GABRA5
MK-0777	2	GABRA5
DARIGABAT	2	GABRA5
BRETAZENIL	2	GABRA5
BASMISANIL	2	GABRA5
AZD7325	2	GABRA5
SARIPIDEM	2	GABRA5
MUSCIMOL	1	GABRA5
GAMMA-AMINOBUTYRIC ACID	1	GABRA5
AZD6280	1	GABRA5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GABRA5	413	Binding:352, Functional:57, Toxicity:3, ADMET:1
CYFIP1	7	Binding:7
MKRN3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP10A	7.6.2.1	P-type phospholipid transporter

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GABRA5	413

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

27 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)
ENZALUTAMIDE	4	GABRA5
DIAZEPAM	4	GABRA5
LIOTHYRONINE	4	GABRA5
GANAXOLONE	4	GABRA5
BREXANOLONE	4	GABRA5
APALUTAMIDE	4	GABRA5
FLUMAZENIL	4	GABRA5
CLONAZEPAM	4	GABRA5
FLUNITRAZEPAM	4	GABRA5
CHLORDIAZEPOXIDE	4	GABRA5
TRIAZOLAM	4	GABRA5
PROPOFOL	4	GABRA5
ALPRAZOLAM	4	GABRA5
DELORAZEPAM	2	GABRA5
FLAVONE	2	GABRA5
PROGABIDE	2	GABRA5
ABECARNIL	2	GABRA5
BAICALEIN	2	GABRA5
MK-0777	2	GABRA5
DARIGABAT	2	GABRA5
BRETAZENIL	2	GABRA5
BASMISANIL	2	GABRA5
AZD7325	2	GABRA5
SARIPIDEM	2	GABRA5
MUSCIMOL	1	GABRA5
GAMMA-AMINOBUTYRIC ACID	1	GABRA5
AZD6280	1	GABRA5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GABRA5
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	10	NDN, SNRPN, NPAP1, ATP10A, CYFIP1, SNHG14, HERC2, APBA2, MAGEL2, MKRN3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NDN	0	—
SNRPN	0	—
NPAP1	0	—
ATP10A	0	—
CYFIP1	7	—
SNHG14	0	—
HERC2	0	—
APBA2	0	—
MAGEL2	0	—
MKRN3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 135.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	72
PHASE3	21
PHASE2	20
PHASE4	7
PHASE1/PHASE2	7
PHASE2/PHASE3	4
PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06901245	PHASE4	RECRUITING	Tirzepatide in PWS, HO and GNSO
NCT01298180	PHASE4	COMPLETED	Is There a Sensibility Increased in the Growth Hormone at Child With Prader-Willi Syndrome?
NCT01542242	PHASE4	TERMINATED	Liraglutide Use in Prader-Willi Syndrome
NCT03031626	PHASE4	COMPLETED	Oxygen Versus Medical Air for Treatment of CSA in Prader Will Syndrome
NCT03616509	PHASE4	COMPLETED	GH in Adults With PWS, Effect on Hypotonia Evaluated by Functional MRI, Relationship With Strength and Body Composition
NCT04066088	PHASE4	WITHDRAWN	Dose Clinical Trial of Guanfacine Extended Release for the Reduction of Aggression and Self-injuries Behavior Associated With Prader-Willi Syndrome
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05701774	PHASE3	ACTIVE_NOT_RECRUITING	Open-Label Extension Study of DCCR in Patients With Prader-Willi Syndrome
NCT06144645	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Evaluation of Non-Invasive Vagus Nerve Stimulation for Temper Outbursts in People With PWS
NCT06366464	PHASE3	RECRUITING	A Study of Pitolisant in Patients With Prader-Willi Syndrome
NCT07219485	PHASE3	ENROLLING_BY_INVITATION	A Study of Pitolisant in Participants With Prader-Willi Syndrome
NCT00175305	PHASE3	TERMINATED	Prader-Willi Syndrome and Appetite
NCT00444964	PHASE3	COMPLETED	Growth Hormone Use in Adults With Prader-Willi Syndrome
NCT00603109	PHASE3	TERMINATED	Effect of Rimonabant on Weight Gain and Body Composition in Adults With Prader Willi Syndrome
NCT02179151	PHASE3	TERMINATED	Double-Blind, Placebo Controlled, Phase 3 Trial of ZGN-440 (Beloranib) in Obese Subjects With Prader-Willi Syndrome
NCT02204163	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Eutropin in Prader-Willi Syndrome
NCT02804373	PHASE2/PHASE3	COMPLETED	Effects of Intranasal Administration of Oxytocin in Adults With Prader-Willi Syndrome
NCT02810483	PHASE3	TERMINATED	Study of the Efficacy of Topiramate in Patients With Prader Willi Syndrome Over 8 Weeks
NCT03440814	PHASE3	COMPLETED	A Study of Diazoxide Choline in Patients With Prader-Willi Syndrome
NCT03554031	PHASE3	UNKNOWN	A Study to Evaluate the Efficacy and Safety of Recombinant Human Growth Hormone Injection in Patients With Prader-Willi Syndrome
NCT03649477	PHASE3	COMPLETED	Phase 3 Study of Intranasal Carbetocin (LV-101) in Patients With Prader-Willi Syndrome
NCT03714373	PHASE3	COMPLETED	Open-Label Extension Study of DCCR in PWS Followed by Double-Blind, Placebo-Controlled, Randomized Withdrawal Period
NCT03790865	PHASE2/PHASE3	TERMINATED	Effects of Livoletide (AZP-531) on Food-related Behaviors in Patients With Prader-Willi Syndrome
NCT04086810	PHASE3	WITHDRAWN	An Open-Label Study of DCCR Tablet in Patients With PWS
NCT04283578	PHASE3	COMPLETED	Oxytocin Treatment in Neonates and Infants With Prader-Willi Syndrome
NCT04697381	PHASE3	COMPLETED	Study of the Efficacy and Safety of Somatropin in Japanese Participants With PWS
NCT05032326	PHASE3	UNKNOWN	Long-term Interventional Follow-up Study of Children With Prader-Willi Syndrome Included in the OTBB3 Clinical Trial
NCT05098509	PHASE2/PHASE3	TERMINATED	A Study to Assess RAD011 (Cannabidiol Oral Solution) for the Treatment of Participants With Prader-Willi Syndrome
NCT05298085	PHASE2/PHASE3	COMPLETED	Effect of Intranasal Oxytocin on Dysphagia in Children and Adolescents With Prader-Willi Syndrome
NCT05387798	PHASE3	WITHDRAWN	A Phase 3 Extension Study of RAD011 (Cannabidiol Oral Solution) in Patients With Prader-Willi Syndrome
NCT06828861	PHASE3	SUSPENDED	ARD-101 for Treatment of PWS: The Hunger Elimination or Reduction Objective Trial
NCT07197034	PHASE3	SUSPENDED	The Hunger Elimination or Reduction Objective (HERO ) Open -Label Extension (OLE) Trial
NCT06239116	PHASE1/PHASE2	RECRUITING	A Study of RM-718 in Healthy Subjects and Patients With MC4R Pathway Impairment
NCT06772597	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Setmelanotide in Patients With Prader-Willi Syndrome
NCT07266324	PHASE2	NOT_YET_RECRUITING	A 2-Part Study to Assess Efficacy, Safety and Tolerability of BMB-101 for the Treatment of Patients With Prader-Willi Syndrome.
NCT07348601	PHASE2	RECRUITING	A Study of CSTI-500 in Patients With Prader-Willi Syndrome
NCT00742664	PHASE1/PHASE2	COMPLETED	Behavioral Treatment of Obsessive-Compulsive Symptoms in Youth With Prader-Willi Syndrome: A Pilot Project
NCT01038570	PHASE2	COMPLETED	Comparative Study Between Prader-Willi Patients Who Take Oxytocin Versus Placebo
NCT01548521	PHASE1/PHASE2	COMPLETED	Tolerance of Intranasal Administration of OT in Prader-Willi Newborn Babies
NCT01818921	PHASE2	COMPLETED	An Efficacy, Safety, and Pharmacokinetics Study of Beloranib in Obese Subjects With Prader-Willi Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PITOLISANT	4	9
OCTREOTIDE	4	3
CANNABIDIOL	4	2
SETMELANOTIDE	4	2
CARBETOCIN	4	1
LIRAGLUTIDE	4	1
OXYTOCIN	4	1
RIMONABANT	4	1
SOMATROPIN	4	1
TIRZEPATIDE	4	1
UBIDECARENONE	3	1
DENATONIUM ACETATE MONOHYDRATE	2	3
CANNABIDIVARIN	2	1
LIVOLETIDE	2	1
NNZ-2591	2	1
CHEMBL4067491	0	2
CHEMBL439305	0	1
CHEMBL4524066	0	1
CHEMBL4645029	0	1
CHEMBL4785366	0	1
CHEMBL5219405	0	1
CHEMBL5275397	0	1
CHEMBL5287934	0	1
CHEMBL5405257	0	1
CHEMBL4303358	0	1
CHEMBL3350037	0	1