Peroxisome biogenesis disorder

Summary

Peroxisome biogenesis disorder (MONDO:0019234) is a disease caused by variants in PEX10, PEX12, PEX14, and 9 other genes, with 19 cohort genes and 5 clinical trials. The dominant Reactome pathway is Class I peroxisomal membrane protein import (9 cohort genes). Top therapeutic interventions include betaine, hydroxychloroquine, and glycinebetaine.

At a glance

• Prevalence: 1-9 / 100 000 (United States) [Orphanet-validated]
• Causal genes: PEX10 (GenCC Definitive), PEX12 (GenCC Definitive), PEX14 (GenCC Definitive), PEX2 (GenCC Definitive) (+8 more)
• Cohort genes: 19
• ClinVar variants: 2,293
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	2	United States	Validated
Prevalence at birth	1-9 / 1 000 000	0.2	Japan	Validated
Point prevalence	1-9 / 100 000		United States	Not yet validated
Point prevalence	1-9 / 1 000 000		Japan	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder
Mondo ID	MONDO:0019234
MeSH	C531857, C536664
OMIM	214100
Orphanet	79189
DOID	DOID:0080377
ICD-11	1919322367
NCIT	C146639, C155747
SNOMED CT	742876007
UMLS	C1832200
MedGen	330407
GARD	0011890
Is cancer (heuristic)	no

Also known as: cerebrohepatorenal syndrome · disorders of peroxisome biogenesis · PBD, ZSS · PBD-Zellweger spectrum disorder · PBD-ZSD · PBD-ZSS · peroxisomal biogenesis disorders · peroxisomal biogenesis disorders, Zellweger syndrome spectrum · peroxisome biogenesis disorder · peroxisome biogenesis disorder spectrum · peroxisome biogenesis disorder-Zellweger syndrome spectrum · peroxisome biogenesis disorders, Zellweger syndrome spectrum · Zellweger spectrum · Zellweger spectrum disorder · Zellweger spectrum disorders · Zellweger syndrome spectrum · ZSD

Data availability: 2,293 ClinVar variants · 18 GenCC gene-disease records · 21 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › peroxisome biogenesis disorder

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

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:

269 uncertain significance, 246 likely benign, 38 pathogenic, 23 pathogenic/likely pathogenic, 12 likely pathogenic, 8 conflicting classifications of pathogenicity, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1451521	NM_000466.3(PEX1):c.56_80del (p.Val19fs)	LOC129998796	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098755	NM_000466.3(PEX1):c.788_789del (p.Thr263fs)	PEX1	Pathogenic	criteria provided, multiple submitters, no conflicts
1098815	NM_000466.3(PEX1):c.130-2A>T	PEX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069736	NM_000286.3(PEX12):c.910_911del (p.Cys304fs)	PEX12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069798	NM_004813.4(PEX16):c.65_71del (p.Thr22fs)	PEX16	Pathogenic	criteria provided, single submitter
1072383	NM_004813.4(PEX16):c.115C>T (p.Arg39Ter)	PEX16	Pathogenic	criteria provided, single submitter
1366308	NM_004813.4(PEX16):c.446dup (p.Ala150fs)	PEX16	Pathogenic	criteria provided, single submitter
1415802	NM_004813.4(PEX16):c.718C>T (p.Gln240Ter)	PEX16	Pathogenic	criteria provided, single submitter
1455420	NM_004813.4(PEX16):c.737G>A (p.Trp246Ter)	PEX16	Pathogenic	criteria provided, single submitter
1456790	NM_004813.4(PEX16):c.451C>T (p.Gln151Ter)	PEX16	Pathogenic	criteria provided, single submitter
1521989	NM_002857.4(PEX19):c.161C>T (p.Ser54Leu)	PEX19	Pathogenic	criteria provided, multiple submitters, no conflicts
13704	NM_000318.3(PEX2):c.355C>T (p.Arg119Ter)	PEX2	Pathogenic	criteria provided, multiple submitters, no conflicts
139588	NM_000318.3(PEX2):c.279_283del (p.Arg94fs)	PEX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1514085	NM_001127649.3(PEX26):c.667+2T>C	PEX26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457724	NM_003630.3(PEX3):c.17G>A (p.Trp6Ter)	PEX3	Pathogenic	criteria provided, multiple submitters, no conflicts
1019386	NM_000287.4(PEX6):c.2585G>T (p.Gly862Val)	PEX6	Pathogenic	criteria provided, single submitter
1069504	NM_000287.4(PEX6):c.727C>T (p.Gln243Ter)	PEX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069607	NM_000287.4(PEX6):c.1027del (p.Arg343fs)	PEX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071121	NM_000287.4(PEX6):c.1691del (p.Cys564fs)	PEX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071131	NM_000287.4(PEX6):c.1216dup (p.His406fs)	PEX6	Pathogenic	criteria provided, single submitter
1072637	NM_000287.4(PEX6):c.1798C>T (p.Gln600Ter)	PEX6	Pathogenic	criteria provided, single submitter
1073363	NM_000287.4(PEX6):c.1357del (p.Leu453fs)	PEX6	Pathogenic	criteria provided, single submitter
1073536	NM_000287.4(PEX6):c.10_216delinsCCACCCGGGGGCCCGTGGCCGGCGGCGGAGCTGGGCCTGGTGCTGGCCCTGAGGC (p.Ala4fs)	PEX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073678	NM_000287.4(PEX6):c.1681del (p.Leu561fs)	PEX6	Pathogenic	criteria provided, single submitter
1073936	NM_000287.4(PEX6):c.747G>A (p.Trp249Ter)	PEX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075322	NM_000287.4(PEX6):c.706C>T (p.Gln236Ter)	PEX6	Pathogenic	criteria provided, single submitter
1075830	NM_000287.4(PEX6):c.1805del (p.Leu602fs)	PEX6	Pathogenic	criteria provided, single submitter
1323439	NM_000287.4(PEX6):c.1313dup (p.Glu439fs)	PEX6	Pathogenic	criteria provided, multiple submitters, no conflicts
1324885	NM_000287.4(PEX6):c.1326dup (p.Ser443fs)	PEX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1356707	NM_000287.4(PEX6):c.531del (p.Pro179fs)	PEX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 94 · Orphanet: 51 · 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
PEX1	Definitive	Autosomal recessive	peroxisome biogenesis disorder 1A (Zellweger)	9
PEX10	Definitive	Autosomal recessive	peroxisome biogenesis disorder	10
PEX12	Definitive	Autosomal recessive	peroxisome biogenesis disorder	7
PEX13	Definitive	Autosomal recessive	peroxisome biogenesis disorder 11A (Zellweger)	5
PEX14	Definitive	Autosomal recessive	peroxisome biogenesis disorder	6
PEX16	Definitive	Autosomal recessive	peroxisome biogenesis disorder 8A (Zellweger)	7
PEX2	Definitive	Autosomal recessive	peroxisome biogenesis disorder	8
PEX26	Definitive	Autosomal recessive	peroxisome biogenesis disorder	7
PEX3	Definitive	Autosomal recessive	peroxisome biogenesis disorder 10A (Zellweger)	6
PEX5	Definitive	Autosomal recessive	peroxisome biogenesis disorder	10
PEX6	Definitive	Autosomal recessive	peroxisome biogenesis disorder	10
PEX7	Definitive	Autosomal recessive	peroxisome biogenesis disorder 9B	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEX26	Orphanet:44	Neonatal adrenoleukodystrophy
PEX26	Orphanet:772	Infantile Refsum disease
PEX26	Orphanet:912	Zellweger syndrome
PEX1	Orphanet:3220	Deafness-enamel hypoplasia-nail defects syndrome
PEX1	Orphanet:44	Neonatal adrenoleukodystrophy
PEX1	Orphanet:772	Infantile Refsum disease
PEX1	Orphanet:912	Zellweger syndrome
PEX10	Orphanet:247815	Autosomal recessive ataxia due to PEX10 deficiency
PEX10	Orphanet:44	Neonatal adrenoleukodystrophy
PEX10	Orphanet:772	Infantile Refsum disease
PEX10	Orphanet:912	Zellweger syndrome
PEX12	Orphanet:44	Neonatal adrenoleukodystrophy
PEX12	Orphanet:772	Infantile Refsum disease
PEX12	Orphanet:912	Zellweger syndrome
PEX13	Orphanet:44	Neonatal adrenoleukodystrophy
PEX13	Orphanet:772	Infantile Refsum disease
PEX13	Orphanet:912	Zellweger syndrome
PEX16	Orphanet:44	Neonatal adrenoleukodystrophy
PEX16	Orphanet:642954	Autosomal recessive ataxia due to PEX16 deficiency
PEX16	Orphanet:772	Infantile Refsum disease
PEX16	Orphanet:912	Zellweger syndrome
PEX3	Orphanet:44	Neonatal adrenoleukodystrophy
PEX3	Orphanet:772	Infantile Refsum disease
PEX3	Orphanet:912	Zellweger syndrome
PEX6	Orphanet:3220	Deafness-enamel hypoplasia-nail defects syndrome
PEX6	Orphanet:44	Neonatal adrenoleukodystrophy
PEX6	Orphanet:772	Infantile Refsum disease
PEX6	Orphanet:912	Zellweger syndrome
PEX6	Orphanet:95433	Autosomal recessive spinocerebellar ataxia-blindness-deafness syndrome
PEX7	Orphanet:309789	Rhizomelic chondrodysplasia punctata type 1
PEX7	Orphanet:773	Adult Refsum disease
PEX2	Orphanet:44	Neonatal adrenoleukodystrophy
PEX2	Orphanet:642965	Autosomal recessive ataxia due to PEX2 deficiency
PEX2	Orphanet:772	Infantile Refsum disease
PEX2	Orphanet:912	Zellweger syndrome
PEX5	Orphanet:44	Neonatal adrenoleukodystrophy
PEX5	Orphanet:468717	Rhizomelic chondrodysplasia punctata type 5
PEX5	Orphanet:772	Infantile Refsum disease
PEX5	Orphanet:912	Zellweger syndrome
PEX14	Orphanet:44	Neonatal adrenoleukodystrophy
PEX14	Orphanet:772	Infantile Refsum disease
PEX14	Orphanet:912	Zellweger syndrome
PHF21A	Orphanet:52022	Potocki-Shaffer syndrome
GATAD1	Orphanet:154	Familial isolated dilated cardiomyopathy
PEX11B	Orphanet:44	Neonatal adrenoleukodystrophy
PEX11B	Orphanet:772	Infantile Refsum disease
PEX11B	Orphanet:912	Zellweger syndrome
PPP2R5D	Orphanet:457279	Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome
PEX19	Orphanet:44	Neonatal adrenoleukodystrophy
PEX19	Orphanet:772	Infantile Refsum disease

Cohort genes → proteins

19 cohort genes, 19 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	19

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PEX26	HGNC:22965	ENSG00000215193	Q7Z412	Peroxisome assembly protein 26	gencc,clinvar
PEX1	HGNC:8850	ENSG00000127980	O43933	Peroxisomal ATPase PEX1	gencc,clinvar
PEX10	HGNC:8851	ENSG00000157911	O60683	Peroxisome biogenesis factor 10	gencc,clinvar
PEX12	HGNC:8854	ENSG00000108733	O00623	Peroxisome assembly protein 12	gencc,clinvar
PEX13	HGNC:8855	ENSG00000162928	Q92968	Peroxisomal membrane protein PEX13	gencc,clinvar
PEX16	HGNC:8857	ENSG00000121680	Q9Y5Y5	Peroxisomal membrane protein PEX16	gencc,clinvar
PEX3	HGNC:8858	ENSG00000034693	P56589	Peroxisomal biogenesis factor 3	gencc,clinvar
PEX6	HGNC:8859	ENSG00000124587	Q13608	Peroxisomal ATPase PEX6	gencc,clinvar
PEX7	HGNC:8860	ENSG00000112357	O00628	Peroxisomal targeting signal 2 receptor	gencc,clinvar
PEX2	HGNC:9717	ENSG00000164751	P28328	Peroxisome biogenesis factor 2	gencc,clinvar
PEX5	HGNC:9719	ENSG00000139197	P50542	Peroxisomal targeting signal 1 receptor	gencc,clinvar
PEX14	HGNC:8856	ENSG00000142655	O75381	Peroxisomal membrane protein PEX14	gencc
CRY2	HGNC:2385	ENSG00000121671	Q49AN0	Cryptochrome-2	clinvar
PHF21A	HGNC:24156	ENSG00000135365	Q96BD5	PHD finger protein 21A	clinvar
GATAD1	HGNC:29941	ENSG00000157259	Q8WUU5	GATA zinc finger domain-containing protein 1	clinvar
MEA1	HGNC:6986	ENSG00000124733	Q16626	Male-enhanced antigen 1	clinvar
PEX11B	HGNC:8853	ENSG00000131779	O96011	Peroxisomal membrane protein 11B	clinvar
PPP2R5D	HGNC:9312	ENSG00000112640	Q14738	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform	clinvar
PEX19	HGNC:9713	ENSG00000162735	P40855	Peroxisomal biogenesis factor 19	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEX26	Peroxisome assembly protein 26	Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes.
PEX1	Peroxisomal ATPase PEX1	Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling.
PEX10	Peroxisome biogenesis factor 10	E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.
PEX12	Peroxisome assembly protein 12	Component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.
PEX13	Peroxisomal membrane protein PEX13	Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor.
PEX16	Peroxisomal membrane protein PEX16	Required for peroxisome membrane biogenesis.
PEX3	Peroxisomal biogenesis factor 3	Involved in peroxisome biosynthesis and integrity.
PEX6	Peroxisomal ATPase PEX6	Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling.
PEX7	Peroxisomal targeting signal 2 receptor	Receptor required for the peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal.
PEX2	Peroxisome biogenesis factor 2	E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.
PEX5	Peroxisomal targeting signal 1 receptor	Receptor that mediates peroxisomal import of proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type).
PEX14	Peroxisomal membrane protein PEX14	Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor.
CRY2	Cryptochrome-2	Transcriptional repressor which forms a core component of the circadian clock.
PHF21A	PHD finger protein 21A	Component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells.
GATAD1	GATA zinc finger domain-containing protein 1	Component of some chromatin complex recruited to chromatin sites methylated ‘Lys-4’ of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3).
MEA1	Male-enhanced antigen 1	May play an important role in spermatogenesis and/or testis development.
PEX11B	Peroxisomal membrane protein 11B	Involved in peroxisomal proliferation.
PPP2R5D	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform	The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.
PEX19	Peroxisomal biogenesis factor 19	Necessary for early peroxisomal biogenesis.

Protein-family classification

Druggable: 2 · Difficult: 7 · Unknown: 10 · Druggable fraction: 0.11

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	5	2.2×	0.283
Scaffold/PPI	2	1.8×	0.603
Enzyme (other)	2	1.3×	0.638
Other/Unknown	10	0.9×	0.697

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEX26	Other/Unknown	no		Pex26
PEX1	Enzyme (other)	yes	3.6.4.7	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
PEX10	Transcription factor	no		Znf_RING, Pex_N, Znf_RING/FYVE/PHD
PEX12	Transcription factor	no		Pex_N, Znf_RING/FYVE/PHD, PEX12
PEX13	Scaffold/PPI	no		SH3_domain, Peroxin-13_N, Pex13
PEX16	Other/Unknown	no		Pex16
PEX3	Other/Unknown	no		Peroxin-3
PEX6	Enzyme (other)	yes	3.6.4.7	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
PEX7	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
PEX2	Transcription factor	no		Znf_RING, Pex_N, Znf_RING/FYVE/PHD
PEX5	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, PEX5/PEX5L
PEX14	Other/Unknown	no		Pex14_N, PEX14, WH-like_DNA-bd_sf
CRY2	Other/Unknown	no		Cryptochrome/DNA_photolyase_1, Cryptochr/Photolyase_FAD-bd, DNA_photolyase_N
PHF21A	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
GATAD1	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, GATAD1
MEA1	Other/Unknown	no		MEA1
PEX11B	Other/Unknown	no		PEX11
PPP2R5D	Other/Unknown	no		PP2A_B56, ARM-like, ARM-type_fold
PEX19	Other/Unknown	no		Pex19, Pex19_C_sf

Expression context

Cohort genes with no expression data: 0.

18 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)	19
unknown	0

Top tissues across cohort

Tissue	Cohort genes
tendon of biceps brachii	3
mucosa of transverse colon	2
body of pancreas	2
secondary oocyte	2
sperm	2
prefrontal cortex	2
right uterine tube	2
gastrocnemius	2
left testis	2
right testis	2
hindlimb stylopod muscle	2
cortical plate	1
calcaneal tendon	1
mucosa of stomach	1
C1 segment of cervical spinal cord	1
parotid gland	1
choroid plexus epithelium	1
primordial germ cell in gonad	1
oocyte	1
granulocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEX26	253	ubiquitous	marker	mucosa of transverse colon, tendon of biceps brachii, cortical plate
PEX1	279	ubiquitous	marker	calcaneal tendon, body of pancreas, mucosa of stomach
PEX10	266	ubiquitous	marker	parotid gland, tendon of biceps brachii, C1 segment of cervical spinal cord
PEX12	270	ubiquitous	yes	secondary oocyte, choroid plexus epithelium, primordial germ cell in gonad
PEX13	264	ubiquitous	marker	secondary oocyte, sperm, oocyte
PEX16	281	ubiquitous	marker	prefrontal cortex, granulocyte, right lobe of liver
PEX3	291	ubiquitous	marker	adrenal tissue, endothelial cell, right adrenal gland cortex
PEX6	227	ubiquitous	marker	right uterine tube, body of pancreas, mucosa of transverse colon
PEX7	276	ubiquitous	marker	pigmented layer of retina, sperm, esophagus squamous epithelium
PEX2	291	ubiquitous	marker	seminal vesicle, ventricular zone, olfactory segment of nasal mucosa
PEX5	142	ubiquitous	marker	gastrocnemius, left testis, right testis
PEX14	286	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
CRY2	270	ubiquitous	marker	hindlimb stylopod muscle, right hemisphere of cerebellum, skin of leg
PHF21A	283	ubiquitous	marker	tendon of biceps brachii, blood, colonic epithelium
GATAD1	287	ubiquitous	marker	left ovary, right uterine tube, inferior vagus X ganglion
MEA1	293	ubiquitous	marker	left testis, right testis, adult organism
PEX11B	289	ubiquitous	marker	prefrontal cortex, Brodmann (1909) area 9, medial globus pallidus
PPP2R5D	285	ubiquitous	marker	olfactory bulb, type B pancreatic cell, ganglionic eminence
PEX19	282	ubiquitous	marker	hindlimb stylopod muscle, muscle of leg, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 91.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHF21A	3,022
PEX6	2,620
CRY2	2,589
PEX19	2,544
PEX1	2,413
PPP2R5D	2,179
PEX3	1,838
PEX5	1,741
PEX7	1,356
PEX11B	1,331

Intra-cohort edges

A	B	Sources
CRY2	PPP2R5D	biogrid_interaction
MEA1	PPP2R5D	string_interaction
PEX1	PEX10	string_interaction
PEX1	PEX12	string_interaction
PEX1	PEX13	string_interaction
PEX1	PEX14	string_interaction
PEX1	PEX16	string_interaction
PEX1	PEX19	string_interaction
PEX1	PEX2	string_interaction
PEX1	PEX26	biogrid_interaction, string_interaction
PEX1	PEX3	string_interaction
PEX1	PEX5	string_interaction
PEX1	PEX6	biogrid_interaction, intact
PEX1	PEX7	string_interaction
PEX10	PEX11B	string_interaction
PEX10	PEX12	biogrid_interaction, string_interaction
PEX10	PEX13	string_interaction
PEX10	PEX14	intact, string_interaction
PEX10	PEX16	string_interaction
PEX10	PEX19	intact, string_interaction
PEX10	PEX2	biogrid_interaction, string_interaction
PEX10	PEX26	string_interaction
PEX10	PEX3	string_interaction
PEX10	PEX5	biogrid_interaction, intact, string_interaction
PEX10	PEX6	string_interaction
PEX10	PEX7	string_interaction
PEX11B	PEX12	string_interaction
PEX11B	PEX13	string_interaction
PEX11B	PEX14	string_interaction
PEX11B	PEX16	string_interaction
PEX11B	PEX19	biogrid_interaction, intact, string_interaction
PEX11B	PEX2	string_interaction
PEX11B	PEX3	string_interaction
PEX11B	PEX5	string_interaction
PEX11B	PEX6	string_interaction
PEX11B	PEX7	string_interaction
PEX12	PEX13	string_interaction
PEX12	PEX14	string_interaction
PEX12	PEX16	string_interaction
PEX12	PEX19	string_interaction
PEX12	PEX2	intact, string_interaction
PEX12	PEX26	string_interaction
PEX12	PEX3	string_interaction
PEX12	PEX5	biogrid_interaction, intact, string_interaction
PEX12	PEX6	string_interaction
PEX12	PEX7	string_interaction
PEX13	PEX14	biogrid_interaction, intact, string_interaction
PEX13	PEX16	string_interaction
PEX13	PEX19	intact, string_interaction
PEX13	PEX2	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 11 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PEX5	P50542	11
PEX19	P40855	5
PEX14	O75381	4
PEX13	Q92968	3
PEX3	P56589	2
PHF21A	Q96BD5	2
PPP2R5D	Q14738	2
GATAD1	Q8WUU5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PEX7	O00628	95.54
PEX11B	O96011	90.12
CRY2	Q49AN0	85.42
PEX16	Q9Y5Y5	83.07
PEX10	O60683	82.81
PEX12	O00623	81.58
PEX2	P28328	81.17
PEX26	Q7Z412	79.87
PEX6	Q13608	69.87
PEX1	O43933	67.19
MEA1	Q16626	64.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 109. Enrichment computed across 19 evidence-associated genes (17 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 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Class I peroxisomal membrane protein import	9	274.8×	1e-19	PEX26, PEX12, PEX13, PEX16, PEX3, PEX2, PEX11B, PEX14 (+1 more)
Peroxisomal protein import	10	101.8×	2e-17	PEX26, PEX1, PEX10, PEX12, PEX13, PEX6, PEX7, PEX2 (+2 more)
E3 ubiquitin ligases ubiquitinate target proteins	6	68.3×	6e-09	PEX10, PEX12, PEX13, PEX2, PEX5, PEX14
ABC transporters in lipid homeostasis	2	70.7×	0.010	PEX3, PEX19
PP2A-mediated dephosphorylation of key metabolic factors	1	96.0×	0.101	PPP2R5D
Signaling by AXIN mutants	1	61.1×	0.101	PPP2R5D
Signaling by CTNNB1 phospho-site mutants	1	61.1×	0.101	PPP2R5D
Signaling by APC mutants	1	61.1×	0.101	PPP2R5D
Signaling by AMER1 mutants	1	61.1×	0.101	PPP2R5D
Regulation of glycolysis by fructose 2,6-bisphosphate metabolism	1	56.0×	0.101	PPP2R5D
Pexophagy	1	56.0×	0.101	PEX5
ERKs are inactivated	1	51.7×	0.101	PPP2R5D
Glucose metabolism	1	51.7×	0.101	PPP2R5D
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters	1	51.7×	0.101	CRY2
APC truncation mutants have impaired AXIN binding	1	48.0×	0.101	PPP2R5D
AXIN missense mutants destabilize the destruction complex	1	48.0×	0.101	PPP2R5D
Truncations of AMER1 destabilize the destruction complex	1	48.0×	0.101	PPP2R5D
Phosphorylation and nuclear translocation of the CRY:PER:kinase complex	1	48.0×	0.101	CRY2
Signaling by GSK3beta mutants	1	44.8×	0.101	PPP2R5D
CTNNB1 S33 mutants aren’t phosphorylated	1	44.8×	0.101	PPP2R5D
CTNNB1 S37 mutants aren’t phosphorylated	1	44.8×	0.101	PPP2R5D
CTNNB1 S45 mutants aren’t phosphorylated	1	44.8×	0.101	PPP2R5D
CTNNB1 T41 mutants aren’t phosphorylated	1	44.8×	0.101	PPP2R5D
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex	1	42.0×	0.101	CRY2
Beta-catenin phosphorylation cascade	1	39.5×	0.101	PPP2R5D
ERK/MAPK targets	1	39.5×	0.101	PPP2R5D
Platelet sensitization by LDL	1	39.5×	0.101	PPP2R5D
Signaling by WNT in cancer	1	35.4×	0.109	PPP2R5D
MAPK targets/ Nuclear events mediated by MAP kinases	1	32.0×	0.116	PPP2R5D
Co-inhibition by CTLA4	1	30.5×	0.117	PPP2R5D

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein import into peroxisome matrix	10	739.1×	9e-28	PEX26, PEX1, PEX10, PEX12, PEX16, PEX6, PEX7, PEX2 (+2 more)
peroxisome organization	11	464.6×	1e-27	PEX1, PEX10, PEX12, PEX16, PEX3, PEX6, PEX7, PEX2 (+3 more)
protein targeting to peroxisome	7	620.9×	2e-18	PEX1, PEX12, PEX16, PEX6, PEX7, PEX5, PEX19
protein import into peroxisome matrix, receptor recycling	6	760.2×	1e-16	PEX1, PEX10, PEX12, PEX6, PEX2, PEX5
protein import into peroxisome matrix, substrate release	5	887.0×	2e-14	PEX10, PEX12, PEX2, PEX5, PEX14
protein import into peroxisome membrane	5	739.1×	8e-14	PEX26, PEX16, PEX3, PEX5, PEX19
protein import into peroxisome matrix, translocation	4	887.0×	1e-11	PEX13, PEX6, PEX5, PEX14
cellular response to reactive oxygen species	6	129.8×	4e-11	PEX10, PEX12, PEX13, PEX2, PEX5, PEX14
protein import into peroxisome matrix, docking	3	665.2×	4e-08	PEX13, PEX5, PEX14
microtubule-based peroxisome localization	2	887.0×	9e-06	PEX1, PEX13
peroxisome membrane biogenesis	2	591.3×	3e-05	PEX16, PEX19
protein to membrane docking	2	354.8×	7e-05	PEX26, PEX16
protein unfolding	2	354.8×	7e-05	PEX1, PEX6
fatty acid beta-oxidation	3	59.1×	9e-05	PEX7, PEX2, PEX5
peroxisome fission	2	161.3×	3e-04	PEX11B, PEX19
cerebral cortex cell migration	2	161.3×	3e-04	PEX13, PEX5
pexophagy	2	110.9×	7e-04	PEX2, PEX5
very long-chain fatty acid metabolic process	2	80.6×	0.001	PEX2, PEX5
protein quality control for misfolded or incompletely synthesized proteins	2	80.6×	0.001	PEX10, PEX12
neuron migration	3	21.1×	0.001	PEX13, PEX7, PEX5
ER-dependent peroxisome organization	1	887.0×	0.003	PEX16
peroxisome transport along microtubule	1	887.0×	0.003	PEX14
establishment of protein localization to peroxisome	1	887.0×	0.003	PEX19
ER-dependent peroxisome localization	1	887.0×	0.003	PEX16
negative regulation of lipid binding	1	887.0×	0.003	PEX19
regulation of sodium-dependent phosphate transport	1	887.0×	0.003	CRY2
protein monoubiquitination	2	36.2×	0.004	PEX12, PEX2
blue light signaling pathway	1	443.5×	0.006	CRY2
negative regulation of glucocorticoid secretion	1	443.5×	0.006	CRY2
regulation of peroxisome size	1	295.6×	0.009	PEX11B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 19

Druggability breadth: 6 of 19 evidence-associated genes (32%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PEX26	0	0
PEX1	0	0
PEX10	0	0
PEX12	0	0
PEX13	0	0
PEX16	0	0
PEX3	0	0
PEX6	0	0
PEX7	0	0
PEX2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
CRY2	2	Binding:2
PEX16	1	Binding:1
PEX3	1	Binding:1
PEX2	1	Binding:1
PEX14	1	ADMET:1
PPP2R5D	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PEX1	3.6.4.7	peroxisome-assembly ATPase
PEX6	3.6.4.7	peroxisome-assembly ATPase

Pharmacogenomics

Cohort genes with a PharmGKB record: 19; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	PEX1, PEX6
E	Difficult family or no structure, no drug	17	PEX26, PEX10, PEX12, PEX13, PEX16, PEX3, PEX7, PEX2, PEX5, PEX14 (+7 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PEX26	0	—
PEX1	0	—
PEX10	0	—
PEX12	0	—
PEX13	0	—
PEX16	1	—
PEX3	1	—
PEX6	0	—
PEX7	0	—
PEX2	1	—
PEX5	0	—
PEX14	1	—
CRY2	2	—
PHF21A	0	—
GATAD1	0	—
MEA1	0	—
PEX11B	0	—
PPP2R5D	1	—
PEX19	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01838941	PHASE3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT01668186	Not specified	RECRUITING	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
NCT06190626	Not specified	RECRUITING	Longitudinal Prospective Natural History Study of Retinopathy in Zellweger Spectrum Disorder
NCT03440905	Not specified	COMPLETED	Proxy-Reported Symptoms and Quality of Life Survey in Zellweger Spectrum Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BETAINE	4	1
HYDROXYCHLOROQUINE	4	1
GLYCINEBETAINE	0	1