Progressive supranuclear palsy

Summary

Progressive supranuclear palsy (MONDO:0019037) is a disease with 20 cohort genes (40 GWAS associations across 10 studies) and 150 clinical trials. Top therapeutic interventions include rivastigmine, zoledronic acid anhydrous, and apomorphine.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 20
• GWAS associations: 40
• Phenotypes (HPO): 32
• Clinical trials: 150

Clinical features

Epidemiology

Prevalence records

10 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	0.65	Worldwide	Validated
Point prevalence	1-9 / 100 000	5.26	Worldwide	Validated
Point prevalence	1-5 / 10 000	14	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.3	Libyan Arab Jamahiriya	Validated
Annual incidence	1-9 / 1 000 000	0.63	United States	Validated
Annual incidence	1-9 / 1 000 000	0.4	Australia	Validated
Point prevalence	1-9 / 100 000	1.39	United States	Validated
Point prevalence	1-9 / 100 000	3.2	Italy	Validated
Point prevalence	1-5 / 10 000	14	Guadeloupe	Validated
Point prevalence	1-9 / 100 000	3.75	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0000605	Supranuclear gaze palsy	Very frequent (80-99%)
HP:0000623	Supranuclear ophthalmoplegia	Very frequent (80-99%)
HP:0002015	Dysphagia	Very frequent (80-99%)
HP:0002172	Postural instability	Very frequent (80-99%)
HP:0002317	Unsteady gait	Very frequent (80-99%)
HP:0002527	Falls	Very frequent (80-99%)
HP:0002529	Neuronal loss in central nervous system	Very frequent (80-99%)
HP:0012535	Abnormal synaptic transmission	Very frequent (80-99%)
HP:0100710	Impulsivity	Very frequent (80-99%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000511	Vertical supranuclear gaze palsy	Frequent (30-79%)
HP:0000514	Slow saccadic eye movements	Frequent (30-79%)
HP:0000643	Blepharospasm	Frequent (30-79%)
HP:0000712	Emotional lability	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0000737	Irritability	Frequent (30-79%)
HP:0000741	Apathy	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002120	Cerebral cortical atrophy	Frequent (30-79%)
HP:0002171	Gliosis	Frequent (30-79%)
HP:0002200	Pseudobulbar signs	Frequent (30-79%)
HP:0002321	Vertigo	Frequent (30-79%)
HP:0002354	Memory impairment	Frequent (30-79%)
HP:0002381	Aphasia	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0000496	Abnormality of eye movement	Occasional (5-29%)
HP:0000726	Dementia	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0002063	Rigidity	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	progressive supranuclear palsy
Mondo ID	MONDO:0019037
MeSH	D013494
OMIM	601104
Orphanet	683
DOID	DOID:678
ICD-10-CM	G23.1
ICD-11	1493396558
NCIT	C85028
SNOMED CT	192976002, 28978003
UMLS	C0038868
MedGen	21026
GARD	0007471
MedDRA	10036813
NORD	1619
Is cancer (heuristic)	no

Also known as: familial progressive supranuclear palsy (type) · progressive supranuclear ophthalmoplegia · PSP syndrome · Steele-Richardson-Olszewski disease · Steele-Richardson-Olszewski syndrome · supranuclear palsy, progressive

Data availability: 40 GWAS associations (10 studies) · 82 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › progressive supranuclear palsy

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, 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 (4): supranuclear palsy, progressive, 1, supranuclear palsy, progressive, 2, supranuclear palsy, progressive, 3, atypical progressive supranuclear palsy syndrome

Genetics & variants

GWAS landscape

40 GWAS associations across 10 studies. Top hits map to 18 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs8070723	2e-118	MAPT	?	5.11
rs71920662	4e-113		?
rs9468	2e-110	MAPT	C	4.81
rs242557	2e-22	MAPT	G	1.91
rs631312	5e-20	MOBP	A	1.46
rs10675541	7e-19	MOBP	?
rs1768208	5e-17	MOBP	?	1.37
rs57113693	9e-16	STX6	?
rs12203592	6e-15	IRF4	?	1.48
rs1044595	3e-14	STX6	T	1.35
rs7571971	4e-13	EIF2AK3	?	1.33
rs12197948	5e-12	RUNX2	G	1.33
rs1411478	4e-11	STX6	?	1.27
rs7966334	4e-11	SLCO1A2	G	1.66
rs2242367	1e-10	SLC2A13	A	1.37
rs369580	8e-10	TNXB	G	1.43
rs564309	2e-09	TRIM11	?	5.55
rs6547705	1e-08	CD8B	?	1.28
rs35740963	2e-08	RUNX2	?
rs12125383	5e-08	LINC01705	?	1.28
rs6687758	6e-08	LINC01705	?	1.27
rs11568563	7e-08	SLCO1A2	?	1.47
rs6852535	1e-07	IL2 - IL21	?	1.23
rs2142991	3e-07	BMS1 - LINC02623	?	1.3
rs147124286	4e-07	SP1	?
rs2045091	5e-07	ASAP1	?
rs114573015	6e-07	MIR4423 - SYDE2	?
rs621042	8e-07	PIK3C2G	?
rs3088159	1e-06	EHD4	?	0.22
rs2305196	3e-06	HK1	?	0.2

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90451697	Farrell K	2024	2,779	5,584	Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes.
GCST006418	Chen JA	2018	1,646	10,662	Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases.
GCST005320	Broce I	2018	1,114	3,247	Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.
GCST001116	Hoglinger GU	2011	1,069	2,958	Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.
GCST90565775	Garcia-Gonzalez P	2025	446	3,463	A Spanish-Portuguese GWAS of progressive supranuclear palsy reveals a novel risk locus in NFASC.
GCST000015	Melquist S	2007	288	0	Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms.
GCST007845	Chen Z	2019	283	4,472	Genome-wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy.
GCST006276	Jabbari E	2018	130	0	Variation at the TRIM11 locus modifies Progressive Supranuclear Palsy phenotype.
GCST012209	Kouri N	2021	0	0	Latent trait modeling of tau neuropathology in progressive supranuclear palsy.
GCST011977	Jabbari E	2020	0	0	Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	3
Tier 3: regulatory	0
Tier 4: intronic/intergenic	28

MAF distribution

Bucket	Variants
common (>=0.05)	31
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	22
intergenic_variant	5
3_prime_UTR_variant	3
unknown	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs8070723	17	46003698	A>G	0.23	intron_variant	MAPT	2e-118	Tier 4: intronic/intergenic
rs71920662							4e-113	Tier 4: intronic/intergenic
rs9468	17	46024197	T>A,C	0.23	3_prime_UTR_variant	MAPT	2e-110	Tier 2: splice/UTR
rs242557	17	45942346	G>A	0.48	intron_variant	MAPT	2e-22	Tier 4: intronic/intergenic
rs631312	3	39467477	G>A,C,T	0.284	intergenic_variant	MOBP	5e-20	Tier 4: intronic/intergenic
rs10675541	3	39468796	T>TAA,TAC,TACAC	0.05	intron_variant	MOBP	7e-19	Tier 4: intronic/intergenic
rs1768208	3	39481512	T>C,G	0.29	intron_variant	MOBP	5e-17	Tier 4: intronic/intergenic
rs57113693	1	180983158	C>G,T	0.05	intron_variant	STX6	9e-16	Tier 4: intronic/intergenic
rs12203592	6	396321	C>G,T	0.19	intron_variant	IRF4	6e-15	Tier 4: intronic/intergenic
rs1044595	1	180974393	C>G,T	0.406	3_prime_UTR_variant	STX6	3e-14	Tier 2: splice/UTR
rs7571971	2	88595833	T>C	0.26	intron_variant	EIF2AK3	4e-13	Tier 4: intronic/intergenic
rs12197948	6	45487107	A>G	0.356	intron_variant	RUNX2	5e-12	Tier 4: intronic/intergenic
rs1411478	1	180993146	A>C,G	0.42	intron_variant	STX6	4e-11	Tier 4: intronic/intergenic
rs7966334	12	21314281	C>A,G,T	0.055	intron_variant	SLCO1A2	4e-11	Tier 4: intronic/intergenic
rs2242367	12	40019896	G>A	0.282	intron_variant	SLC2A13	1e-10	Tier 4: intronic/intergenic
rs369580	6	32052461	A>G	0.143	intron_variant	TNXB	8e-10	Tier 4: intronic/intergenic
rs564309	1	228397861	C>A	0.19	intron_variant	TRIM11	2e-09	Tier 4: intronic/intergenic
rs6547705	2	86817193	G>A,C,T	0.23	intron_variant	CD8B	1e-08	Tier 4: intronic/intergenic
rs35740963	6	45531877	AT>A,ATT	0.05	intron_variant	RUNX2	2e-08	Tier 4: intronic/intergenic
rs12125383	1	221995092	G>A	0.05	intron_variant	LINC01705	5e-08	Tier 4: intronic/intergenic
rs6687758	1	221991606	A>G	0.19	intron_variant	LINC01705	6e-08	Tier 4: intronic/intergenic
rs11568563	12	21304500	T>A,G	0.05	missense_variant	SLCO1A2	7e-08	Tier 1: coding
rs6852535	4	122557561	G>A,C	0.34	intergenic_variant	IL2 - IL21	1e-07	Tier 4: intronic/intergenic
rs2142991	10	42845657	C>A,G,T	0.17	intergenic_variant	BMS1 - LINC02623	3e-07	Tier 4: intronic/intergenic
rs147124286	12	53394219	GA>G,GAA,GAAA	0.05	intron_variant	SP1	4e-07	Tier 4: intronic/intergenic
rs2045091	8	130063613	C>G,T	0.05	intron_variant	ASAP1	5e-07	Tier 4: intronic/intergenic
rs114573015	1	85137368	A>G	0.05	intergenic_variant	MIR4423 - SYDE2	6e-07	Tier 4: intronic/intergenic
rs621042	12	18636073	C>A,G	0.05	intron_variant	PIK3C2G	8e-07	Tier 4: intronic/intergenic
rs3088159	15	41898494	C>T	0.05	3_prime_UTR_variant	EHD4	1e-06	Tier 2: splice/UTR
rs2305196	10	69384568	G>A,C,T	0.05	intron_variant	HK1	3e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 15 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
MAPT	MAPT	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RUNX2	Orphanet:1452	Cleidocranial dysplasia
RUNX2	Orphanet:2504	Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome
OBSCN	Orphanet:99845	Genetic recurrent myoglobinuria
BMS1	Orphanet:1114	Aplasia cutis congenita
EIF2AK3	Orphanet:1667	Wolcott-Rallison syndrome
IL21	Orphanet:477661	IL21-related infantile inflammatory bowel disease
IRF4	Orphanet:3452	Whipple disease
MAPT	Orphanet:100069	Semantic dementia
MAPT	Orphanet:100070	Progressive non-fluent aphasia
MAPT	Orphanet:240071	Classic progressive supranuclear palsy syndrome
MAPT	Orphanet:240085	Progressive supranuclear palsy-predominant parkinsonism syndrome
MAPT	Orphanet:240094	Progressive supranuclear palsy-pure akinesia with gait freezing syndrome
MAPT	Orphanet:240103	Progressive supranuclear palsy-corticobasal syndrome
MAPT	Orphanet:240112	Progressive supranuclear palsy-progressive non-fluent aphasia syndrome
MAPT	Orphanet:275864	Behavioral variant of frontotemporal dementia

Cohort genes → proteins

20 cohort genes, 19 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	20

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RUNX2	HGNC:10472	ENSG00000124813	Q13950	Runt-related transcription factor 2	gwas
SLCO1A2	HGNC:10956	ENSG00000084453	P46721	Solute carrier organic anion transporter family member 1A2	gwas
SP1	HGNC:11205	ENSG00000185591	P08047	Transcription factor Sp1	gwas
STX6	HGNC:11441	ENSG00000135823	O43752	Syntaxin-6	gwas
TRIM17	HGNC:13430	ENSG00000162931	Q9Y577	E3 ubiquitin-protein ligase TRIM17	gwas
OBSCN	HGNC:15719	ENSG00000154358	Q5VST9	Obscurin	gwas
TRIM11	HGNC:16281	ENSG00000154370	Q96F44	E3 ubiquitin-protein ligase TRIM11	gwas
CD8B	HGNC:1707	ENSG00000172116	P10966	T-cell surface glycoprotein CD8 beta chain	gwas
BMS1	HGNC:23505	ENSG00000165733	Q14692	Ribosome biogenesis protein BMS1 homolog	gwas
ASAP1	HGNC:2720	ENSG00000153317	Q9ULH1	Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1	gwas
DUSP10	HGNC:3065	ENSG00000143507	Q9Y6W6	Dual specificity protein phosphatase 10	gwas
DNAI3	HGNC:30711	ENSG00000162643	Q8IWG1	Dynein axonemal intermediate chain 3	gwas
EIF2AK3	HGNC:3255	ENSG00000172071	Q9NZJ5	Eukaryotic translation initiation factor 2-alpha kinase 3	gwas
MIR4423	HGNC:41784	ENSG00000266110		microRNA 4423	gwas
H3-4	HGNC:4778	ENSG00000168148	Q16695	Histone H3.1t	gwas
IL2	HGNC:6001	ENSG00000109471	P60568	Interleukin-2	gwas
IL21	HGNC:6005	ENSG00000138684	Q9HBE4	Interleukin-21	gwas
IRF4	HGNC:6119	ENSG00000137265	Q15306	Interferon regulatory factor 4	gwas
MAPT	HGNC:6893	ENSG00000186868	P10636	Microtubule-associated protein tau	gwas
MOBP	HGNC:7189	ENSG00000168314	Q13875	Myelin-associated oligodendrocyte basic protein	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RUNX2	Runt-related transcription factor 2	Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis.
SLCO1A2	Solute carrier organic anion transporter family member 1A2	Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate)…
SP1	Transcription factor Sp1	Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli.
STX6	Syntaxin-6	SNARE promoting movement of transport vesicles to target membranes.
TRIM17	E3 ubiquitin-protein ligase TRIM17	E3 ubiquitin ligase that plays important roles in the regulation of neuronal apoptosis, selective autophagy or cell proliferation.
OBSCN	Obscurin	Structural component of striated muscles which plays a role in myofibrillogenesis.
TRIM11	E3 ubiquitin-protein ligase TRIM11	E3 ubiquitin-protein ligase that promotes the degradation of insoluble ubiquitinated proteins, including insoluble PAX6, poly-Gln repeat expanded HTT and poly-Ala repeat expanded ARX.
CD8B	T-cell surface glycoprotein CD8 beta chain	Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses.
BMS1	Ribosome biogenesis protein BMS1 homolog	GTPase required for the synthesis of 40S ribosomal subunits and for processing of pre-ribosomal RNA (pre-rRNA) at sites A0, A1, and A2.
ASAP1	Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1	Possesses phosphatidylinositol 4,5-bisphosphate-dependent GTPase-activating protein activity for ARF1 (ADP ribosylation factor 1) and ARF5 and a lesser activity towards ARF6.
DUSP10	Dual specificity protein phosphatase 10	Protein phosphatase involved in the inactivation of MAP kinases.
DNAI3	Dynein axonemal intermediate chain 3	Acts as a negative regulator of cell migration, invasion, and metastasis downstream of p53/TP53, through inhibition of Arp2/3 complex-mediated actin polymerization.
EIF2AK3	Eukaryotic translation initiation factor 2-alpha kinase 3	Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR).
H3-4	Histone H3.1t	Core component of nucleosome.
IL2	Interleukin-2	Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance.
IL21	Interleukin-21	Cytokine with immunoregulatory activity.
IRF4	Interferon regulatory factor 4	Transcriptional activator.
MAPT	Microtubule-associated protein tau	Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.
MOBP	Myelin-associated oligodendrocyte basic protein	May play a role in compacting or stabilizing the myelin sheath, possibly by binding the negatively charged acidic phospholipids of the cytoplasmic membrane.

Protein-family classification

Druggable: 5 · Difficult: 6 · Unknown: 9 · Druggable fraction: 0.25

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
Phosphatase	1	4.2×	0.399
Transporter	1	3.9×	0.399
Kinase	2	2.8×	0.399
Transcription factor	4	1.6×	0.399
Scaffold/PPI	2	1.7×	0.453
Antibody/Immunoglobulin	1	1.5×	0.586
Other/Unknown	9	0.8×	0.885

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RUNX2	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
SLCO1A2	Transporter	yes		Kazal_dom, OATP, MFS_dom
SP1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
STX6	Other/Unknown	no		T_SNARE_dom, Syntaxin/epimorphin_CS, SNARE
TRIM17	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
OBSCN	Kinase	yes		IQ_motif_EF-hand-BS, DH_dom, Prot_kinase_dom
TRIM11	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
CD8B	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
BMS1	Other/Unknown	no		BMS1_TSR1_C, AARP2CN, P-loop_NTPase
ASAP1	Scaffold/PPI	no		ArfGAP_dom, SH3_domain, PH_domain
DUSP10	Phosphatase	yes	3.1.3.16	Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Rhodanese-like_dom
DNAI3	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
EIF2AK3	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
MIR4423	Other/Unknown	no
H3-4	Other/Unknown	no		Histone_H3/CENP-A, H2A/H2B/H3, Histone-fold
IL2	Other/Unknown	no		IL-2, 4_helix_cytokine-like_core, IL-2_CS
IL21	Other/Unknown	no		IL-15/IL-21_fam, 4_helix_cytokine-like_core
IRF4	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
MAPT	Other/Unknown	no		MAP_tubulin-bd_rpt, Tau, MAP2/MAP4/Tau
MOBP	Other/Unknown	no		FYVE_2, Intracell_Transport_Effector

Expression context

Cohort genes with no expression data: 0.

15 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)	20
unknown	0

Top tissues across cohort

Tissue	Cohort genes
trabecular bone tissue	3
male germ line stem cell (sensu Vertebrata) in testis	3
mucosa of paranasal sinus	2
C1 segment of cervical spinal cord	2
cortical plate	2
cerebellar cortex	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
blood	2
tibia	1
corpus callosum	1
spinal cord	1
nipple	1
skin of hip	1
oocyte	1
secondary oocyte	1
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1
granulocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RUNX2	241	ubiquitous	marker	tibia, mucosa of paranasal sinus, trabecular bone tissue
SLCO1A2	155	tissue_specific	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
SP1	264	ubiquitous	marker	nipple, trabecular bone tissue, skin of hip
STX6	278	ubiquitous	marker	secondary oocyte, oocyte, cortical plate
TRIM17	133	broad	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
OBSCN	197	ubiquitous	marker	hindlimb stylopod muscle, apex of heart, gastrocnemius
TRIM11	237	ubiquitous	yes	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
CD8B	161	tissue_specific	marker	granulocyte, blood, thymus
BMS1	287	ubiquitous	marker	tendon of biceps brachii, body of tongue, pharyngeal mucosa
ASAP1	271	ubiquitous	marker	endothelial cell, sural nerve, trabecular bone tissue
DUSP10	271	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, biceps brachii
DNAI3	160	broad	marker	bronchial epithelial cell, bronchus, right uterine tube
EIF2AK3	286	ubiquitous	marker	body of pancreas, mucosa of paranasal sinus, calcaneal tendon
MIR4423	62		yes	myometrium, adrenal tissue, blood
H3-4	89	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
IL2	92		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell
IL21	26		marker	male germ line stem cell (sensu Vertebrata) in testis, olfactory bulb, type B pancreatic cell
IRF4	180	broad	marker	lymph node, endocervix, vermiform appendix
MAPT	141	broad	marker	cortical plate, superior frontal gyrus, prefrontal cortex
MOBP	201	tissue_specific	marker	C1 segment of cervical spinal cord, cranial nerve II, pons

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
H3-4	9,547
MAPT	7,289
SP1	4,275
RUNX2	4,101
EIF2AK3	4,018
BMS1	3,587
IRF4	3,450
STX6	2,852
OBSCN	2,042
DUSP10	1,952

Intra-cohort edges

A	B	Sources
MOBP	STX6	string_interaction

Structural data

PDB: 15 · AlphaFold-only: 4 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAPT	P10636	293
IL2	P60568	37
OBSCN	Q5VST9	25
DUSP10	Q9Y6W6	23
IRF4	Q15306	19
EIF2AK3	Q9NZJ5	15
H3-4	Q16695	13
SP1	P08047	11
ASAP1	Q9ULH1	5
RUNX2	Q13950	4
BMS1	Q14692	3
IL21	Q9HBE4	3
STX6	O43752	2
TRIM11	Q96F44	1
DNAI3	Q8IWG1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRIM17	Q9Y577	86.17
CD8B	P10966	82.03
SLCO1A2	P46721	79.97
MOBP	Q13875	55.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 138. Enrichment computed across 20 evidence-associated genes (18 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 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX2 regulates chondrocyte maturation	1	126.9×	0.127	RUNX2
RUNX2 regulates genes involved in differentiation of myeloid cells	1	126.9×	0.127	RUNX2
Ciprofloxacin ADME	1	126.9×	0.127	SLCO1A2
Nef Mediated CD8 Down-regulation	1	90.6×	0.127	CD8B
Signaling by MAPK mutants	1	90.6×	0.127	DUSP10
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	79.3×	0.127	RUNX2
RUNX2 regulates genes involved in cell migration	1	79.3×	0.127	RUNX2
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	63.4×	0.127	IL2
Interleukin-21 signaling	1	63.4×	0.127	IL21
Organic anion transport by SLCO transporters	1	57.7×	0.127	SLCO1A2
Regulation of CDH11 gene transcription	1	57.7×	0.127	SP1
Caspase-mediated cleavage of cytoskeletal proteins	1	52.9×	0.127	MAPT
Interleukin-2 signaling	1	52.9×	0.127	IL2
ALK mutants bind TKIs	1	52.9×	0.127	EIF2AK3
Positive Regulation of CDH1 Gene Transcription	1	52.9×	0.127	SP1
NFE2L2 regulating tumorigenic genes	1	52.9×	0.127	SP1
PERK regulates gene expression	1	45.3×	0.127	EIF2AK3
RUNX2 regulates bone development	1	45.3×	0.127	RUNX2
Regulation of CDH11 Expression and Function	1	45.3×	0.127	SP1
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	42.3×	0.127	RUNX2
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1	37.3×	0.127	SP1
Regulation of Homotypic Cell-Cell Adhesion	1	37.3×	0.127	SP1
Regulation of Expression and Function of Type II Classical Cadherins	1	37.3×	0.127	SP1
RAF-independent MAPK1/3 activation	1	35.2×	0.127	DUSP10
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	35.2×	0.127	CD8B
The role of Nef in HIV-1 replication and disease pathogenesis	1	35.2×	0.127	CD8B
Recycling of bile acids and salts	1	33.4×	0.127	SLCO1A2
Modulation of host responses by IFN-stimulated genes	1	33.4×	0.127	EIF2AK3
Signaling by ALK fusions and activated point mutants	2	16.7×	0.127	EIF2AK3, IRF4
Metabolism of steroids	2	15.3×	0.127	SLCO1A2, SP1

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
positive regulation of tissue remodeling	2	295.6×	0.004	IL2, IL21
chondrocyte development	2	98.5×	0.015	RUNX2, EIF2AK3
positive regulation of regulatory T cell differentiation	2	98.5×	0.015	DUSP10, IL2
ligamentous ossification	1	887.0×	0.020	RUNX2
plus-end-directed organelle transport along microtubule	1	887.0×	0.020	MAPT
cellular response to wortmannin	1	887.0×	0.020	SP1
positive regulation of hydrogen sulfide biosynthetic process	1	887.0×	0.020	SP1
negative regulation of epithelium regeneration	1	887.0×	0.020	DUSP10
positive regulation of interleukin-17 production	2	63.4×	0.020	IL2, IL21
positive regulation of immunoglobulin production	2	50.7×	0.020	IL2, IL21
cell maturation	2	46.7×	0.020	RUNX2, IL21
regulation of cell differentiation	2	45.5×	0.020	RUNX2, H3-4
positive regulation of interleukin-10 production	2	42.2×	0.020	IL21, IRF4
T cell differentiation	2	40.3×	0.020	RUNX2, IL2
positive regulation of B cell proliferation	2	36.2×	0.023	IL2, IL21
protein localization to M-band	1	443.5×	0.024	OBSCN
response to tacrolimus	1	443.5×	0.024	IL2
regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1	443.5×	0.024	EIF2AK3
neurofibrillary tangle assembly	1	443.5×	0.024	MAPT
negative regulation of protein localization to mitochondrion	1	443.5×	0.024	MAPT
regulation of CD4-positive, alpha-beta T cell proliferation	1	443.5×	0.024	IL2
osteoblast fate commitment	1	295.6×	0.024	RUNX2
leukocyte activation involved in immune response	1	295.6×	0.024	IL2
synaptic vesicle to endosome fusion	1	295.6×	0.024	STX6
negative regulation of translation in response to stress	1	295.6×	0.024	EIF2AK3
regulation of translation initiation in response to endoplasmic reticulum stress	1	295.6×	0.024	EIF2AK3
regulation of T cell homeostatic proliferation	1	295.6×	0.024	IL2
negative regulation of AIM2 inflammasome complex assembly	1	295.6×	0.024	TRIM11
positive regulation of membrane tubulation	1	295.6×	0.024	ASAP1
bone mineralization	2	28.6×	0.024	RUNX2, EIF2AK3

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Rasagiline	Phase 3 (in late-stage trials)
Riluzole	Phase 3 (in late-stage trials)
Rivastigmine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Donepezil, Tertomotide, Ubidecarenone, Valproic Acid.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 5 · Undrugged: 15

Druggability breadth: 9 of 20 evidence-associated genes (45%) 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
SLCO1A2	RIFAMPIN
MAPT	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPT	449	4
SLCO1A2	2	4
IL2	2	2
SP1	1	2
EIF2AK3	1	1
RUNX2	0	0
STX6	0	0
TRIM17	0	0
OBSCN	0	0
TRIM11	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIFAMPIN	4	MAPT, SLCO1A2
RIFAMYCIN	4	SLCO1A2
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
FLUORESCEIN	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT
AMIODARONE HYDROCHLORIDE	4	MAPT
TRICLABENDAZOLE	4	MAPT
MESORIDAZINE	4	MAPT
INDIGOTINDISULFONATE	4	MAPT
TRIHEXYPHENIDYL HYDROCHLORIDE	4	MAPT
IMIPRAMINE	4	MAPT
FURAZOLIDONE	4	MAPT
DROPERIDOL	4	MAPT
ARIPIPRAZOLE	4	MAPT
RALOXIFENE HYDROCHLORIDE	4	MAPT
IDARUBICIN	4	MAPT
ACETAMINOPHEN	4	MAPT
ACITRETIN	4	MAPT
CISPLATIN	4	MAPT
CLOBETASOL PROPIONATE	4	MAPT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
MAPT	184	Binding:180, Functional:4
EIF2AK3	153	Binding:151, Functional:2
SLCO1A2	70	Functional:60, ADMET:9, Binding:1
IL2	35	Binding:34, ADMET:1
SP1	10	Binding:8, ADMET:2
DUSP10	10	Binding:9, ADMET:1
IRF4	3	Binding:3
ASAP1	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DUSP10	3.1.3.16, 3.1.3.48	protein-serine/threonine phosphatase, protein-tyrosine-phosphatase
EIF2AK3	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EIF2AK3	153
MAPT	184

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

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

Compound	Max phase	Cohort target (bioactivity)
RIFAMPIN	4	MAPT, SLCO1A2
RIFAMYCIN	4	SLCO1A2
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
FLUORESCEIN	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT
AMIODARONE HYDROCHLORIDE	4	MAPT
TRICLABENDAZOLE	4	MAPT
MESORIDAZINE	4	MAPT
INDIGOTINDISULFONATE	4	MAPT
TRIHEXYPHENIDYL HYDROCHLORIDE	4	MAPT
IMIPRAMINE	4	MAPT
FURAZOLIDONE	4	MAPT
DROPERIDOL	4	MAPT
ARIPIPRAZOLE	4	MAPT
RALOXIFENE HYDROCHLORIDE	4	MAPT
IDARUBICIN	4	MAPT
ACETAMINOPHEN	4	MAPT
ACITRETIN	4	MAPT
CISPLATIN	4	MAPT
CLOBETASOL PROPIONATE	4	MAPT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SLCO1A2, MAPT
B	Phased (≥1) drug, not yet approved	3	SP1, EIF2AK3, IL2
C	Druggable family + PDB, no drug	2	OBSCN, DUSP10
D	Druggable family + AlphaFold only, no drug	1	CD8B
E	Difficult family or no structure, no drug	12	RUNX2, STX6, TRIM17, TRIM11, BMS1, ASAP1, DNAI3, MIR4423, H3-4, IL21 (+2 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RUNX2	0	—
STX6	0	—
TRIM17	0	—
OBSCN	0	—
TRIM11	0	—
CD8B	0	—
BMS1	0	—
ASAP1	1	—
DUSP10	10	—
DNAI3	0	—
MIR4423	0	—
H3-4	0	—
IL21	0	—
IRF4	3	—
MOBP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 150.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	95
PHASE2	19
PHASE1	17
EARLY_PHASE1	7
PHASE3	4
PHASE1/PHASE2	4
PHASE2/PHASE3	3
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03924414	PHASE4	ACTIVE_NOT_RECRUITING	Trial of Parkinson’s And Zoledronic Acid
NCT00211224	PHASE3	TERMINATED	Neuroprotection and Natural History in Parkinson’s Plus Syndromes (NNIPPS)
NCT00532571	PHASE2/PHASE3	COMPLETED	Effects of Coenzyme Q10 in PSP and CBD
NCT01110720	PHASE2/PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy
NCT01187888	PHASE3	TERMINATED	Efficacy, Tolerability and Safety of Azilect in Subjects With Progressive Supranuclear Palsy
NCT02839642	PHASE3	COMPLETED	Efficacy of RIVAstigmine on Motor, Cognitive and Behavioural Impairment in Progressive Supranuclear Palsy
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT06122662	PHASE2/PHASE3	COMPLETED	AMX0035 and Progressive Supranuclear Palsy
NCT06162013	PHASE2	RECRUITING	The NADAPT Study: a Randomized Double-blind Trial of NAD Replenishment Therapy for Atypical Parkinsonism
NCT06355531	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Assess the Efficacy, Safety, and Pharmacokinetics of FNP-223 to Slow Progression of Progressive Supranuclear Palsy (PSP)
NCT07173803	PHASE2	NOT_YET_RECRUITING	The Progressive Supranuclear Palsy Clinical Trial Platform
NCT00005903	PHASE2	COMPLETED	Continuously Infused Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (GDNF) to Treat Progressive Supranuclear Palsy
NCT00139373	PHASE2	UNKNOWN	Study of the Distractibility Syndrome in Patients With Progressive Supranuclear Palsy
NCT00328874	PHASE2	COMPLETED	Study About Safety and Efficacy of Coenzyme Q10 in Progressive Supranuclear Palsy
NCT00385710	PHASE2	COMPLETED	Trial of Valproic Acid in Patients With Progressive Supranuclear Palsy (Depakine)
NCT00522015	PHASE2	UNKNOWN	Efficacy Study for Treatment of Dementia in Progressive Supranuclear Palsy
NCT00703677	PHASE1/PHASE2	COMPLETED	A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration
NCT01537549	PHASE1/PHASE2	COMPLETED	Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy
NCT01824121	PHASE1/PHASE2	UNKNOWN	Clinical Trial to Evaluate Bone Marrow Stem Cell Therapy for PSP, a Rare Form of Parkinsonism
NCT02985879	PHASE2	TERMINATED	A Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Subjects With Progressive Supranuclear Palsy (PSP)
NCT03068468	PHASE2	TERMINATED	Study of BIIB092 in Participants With Progressive Supranuclear Palsy
NCT03391765	PHASE2	TERMINATED	An Extension Study of ABBV-8E12 in Progressive Supranuclear Palsy (PSP)
NCT03446807	PHASE2	WITHDRAWN	Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism
NCT04008355	PHASE2	COMPLETED	A Study to Assess Tolerability, Safety, Pharmacokinetics and Effect of AZP2006 in Patients With PSP
NCT04184063	PHASE2	COMPLETED	Study of NBMI Treatment in Patients With Atypical Parkinsons (PSP or MSA)
NCT04253132	PHASE1/PHASE2	UNKNOWN	Evaluation of Tolfenamic Acid in Individuals With PSP at 12-Weeks
NCT04734379	PHASE2	UNKNOWN	Rho Kinase (ROCK) Inhibitor in Tauopathies - 1
NCT04937530	PHASE2	UNKNOWN	RT001 in Patients With Progressive Supranuclear Palsy (PSP) PROGRESSIVE SUPRANUCLEAR PALSY
NCT04993768	PHASE2	COMPLETED	A Phase 2a Study of TPN-101 in Patients With Progressive Supranuclear Palsy (PSP)
NCT05819658	PHASE2	COMPLETED	GV1001 Subcutaneous(SC) for the Treatment of Progressive Supranuclear Palsy (PSP)
NCT06235775	PHASE2	COMPLETED	Administration of GV1001 for the Treatment of Progressive Supranuclear Palsy Who Completed Study GV1001-PSP-CL2-011
NCT04658199	PHASE1	ACTIVE_NOT_RECRUITING	A Study to Test the Safety and Tolerability of Long-term UCB0107 Administration in Study Participants With Progressive Supranuclear Palsy
NCT01056965	PHASE1	COMPLETED	Davunetide (AL-108) in Predicted Tauopathies - Pilot Study
NCT02103894	PHASE1	COMPLETED	Evaluation of [18F]MNI-777 PET as a Marker of Tau Pathology in Subjects With Tauopathies Compared to Healthy Subjects
NCT02133846	PHASE1	COMPLETED	Safety Study of TPI-287 to Treat CBS and PSP
NCT02167594	PHASE1	COMPLETED	Tau Imaging in Subjects With Progressive Supranuclear Palsy, Corticobasal Degeneration and Healthy Volunteers
NCT02422485	PHASE1	COMPLETED	A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy
NCT02460094	PHASE1	COMPLETED	Multiple Ascending Dose Study of Intravenously Administered BMS-986168 (BIIB092) in Patients With Progressive Supranuclear Palsy
NCT02460731	PHASE1	COMPLETED	Young Plasma Transfusions for Progressive Supranuclear Palsy
NCT02494024	PHASE1	COMPLETED	Safety, Tolerability, and Pharmacokinetics of C2N-8E12 in Subjects With Progressive Supranuclear Palsy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RIVASTIGMINE	4	6
ZOLEDRONIC ACID ANHYDROUS	4	3
APOMORPHINE	4	1
DONEPEZIL	4	1
DROXIDOPA	4	1
FLORTAUCIPIR F 18	4	1
FLUTEMETAMOL	4	1
IOFLUPANE I 123	4	1
NIACINAMIDE	4	1
RASAGILINE	4	1
RILUZOLE	4	1
TIPIRACIL HYDROCHLORIDE	4	1
VALPROIC ACID	4	1
UBIDECARENONE	3	3
TERTOMOTIDE	3	2
CREATINE	3	1
FASUDIL	3	1
FLUORIDE ION F-18	3	1
LEUCINE	3	1
LIPOIC ACID, ALPHA	3	1
LITHIUM	3	1
NICOTINAMIDE RIBOSIDE	3	1
GOSURANEMAB	2	3
TILAVONEMAB	2	3
BEPRANEMAB	2	2
DAVUNETIDE	2	2
COSFROVIXIMAB	2	1
PYRUVATE	2	1
SALSALATE	2	1
TIDEGLUSIB	2	1