Intellectual disability, autosomal dominant 47

Summary

Intellectual disability, autosomal dominant 47 (MONDO:0030912) is a disease caused by STAG1 (GenCC Definitive), with 4 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: STAG1 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 70
• Phenotypes (HPO): 38

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		17	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

38 HPO clinical features (Orphanet curated; top 38 by frequency):

HPO ID	Term	Frequency
HP:0000490	Deeply set eye	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000154	Wide mouth	Frequent (30-79%)
HP:0000426	Prominent nasal bridge	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0002020	Gastroesophageal reflux	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0045074	Thin eyebrow	Frequent (30-79%)
HP:0000050	Hypoplastic male external genitalia	Occasional (5-29%)
HP:0000085	Horseshoe kidney	Occasional (5-29%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000527	Long eyelashes	Occasional (5-29%)
HP:0000664	Synophrys	Occasional (5-29%)
HP:0000954	Single transverse palmar crease	Occasional (5-29%)
HP:0000965	Cutis marmorata	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001377	Limited elbow extension	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001566	Widely-spaced maxillary central incisors	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002817	Abnormality of the upper limb	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0004691	2-3 toe syndactyly	Occasional (5-29%)
HP:0010864	Intellectual disability, severe	Occasional (5-29%)
HP:0012444	Brain atrophy	Occasional (5-29%)
HP:0200134	Epileptic encephalopathy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 47
Mondo ID	MONDO:0030912
OMIM	617635
Orphanet	502434
DOID	DOID:0080238
UMLS	C4539951
MedGen	1622196
GARD	0017935
Is cancer (heuristic)	no

Also known as: autosomal dominant mental retardation 47 · intellectual disability, autosomal dominant 47 · mental retardation, autosomal dominant 47 · MRD47 · STAG1-related intellectual disability-facial dysmorphism-gastroesophageal reflux syndrome

Data availability: 70 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › intellectual disability, autosomal dominant 47

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

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

70 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 17 likely pathogenic, 8 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 4 pathogenic, 2 benign/likely benign, 2 likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2441671	NM_005862.3(STAG1):c.418C>T (p.Arg140Ter)	STAG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3772689	NM_005862.3(STAG1):c.395-2A>T	STAG1	Pathogenic	criteria provided, single submitter
437896	NC_000003.11:g.136254742_136427833del	STAG1	Pathogenic	no assertion criteria provided
437897	NM_005862.3(STAG1):c.1433A>C (p.His478Pro)	STAG1	Pathogenic/Likely pathogenic	no assertion criteria provided
437898	NM_005862.3(STAG1):c.646A>G (p.Arg216Gly)	STAG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437899	NM_005862.3(STAG1):c.1118G>A (p.Arg373Gln)	STAG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437900	NM_005862.3(STAG1):c.1460_1464dup (p.Trp489fs)	STAG1	Pathogenic/Likely pathogenic	no assertion criteria provided
523187	NM_005862.3(STAG1):c.1129C>T (p.Arg377Cys)	STAG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802013	NM_005862.3(STAG1):c.260del (p.Leu87fs)	STAG1	Pathogenic	criteria provided, single submitter
995415	NM_005862.3(STAG1):c.391C>T (p.Arg131Ter)	STAG1	Pathogenic	criteria provided, single submitter
523199	GRCh37/hg19 3q22.1-22.3(chr3:132642704-136360844)x1	AMOTL2	Likely pathogenic	criteria provided, single submitter
523198	GRCh38/hg38 3q22.2-22.3(chr3:135423479-136961152)x1	IL20RB	Likely pathogenic	criteria provided, single submitter
523197	GRCh38/hg38 3q22.2-22.3(chr3:135343568-136642002)x1	LOC112903838	Likely pathogenic	criteria provided, single submitter
1325144	NM_005862.3(STAG1):c.513del (p.Gln170_Trp171insTer)	STAG1	Likely pathogenic	criteria provided, single submitter
1333942	NM_005862.3(STAG1):c.625G>C (p.Gly209Arg)	STAG1	Likely pathogenic	criteria provided, single submitter
1709088	NM_005862.3(STAG1):c.3691C>T (p.Arg1231Ter)	STAG1	Likely pathogenic	criteria provided, single submitter
1709726	NM_005862.3(STAG1):c.1716dup (p.Ile573fs)	STAG1	Likely pathogenic	criteria provided, single submitter
2580172	NM_005862.3(STAG1):c.1962dup (p.Asp655Ter)	STAG1	Likely pathogenic	criteria provided, single submitter
2690892	NM_005862.3(STAG1):c.3241C>T (p.Arg1081Ter)	STAG1	Likely pathogenic	criteria provided, single submitter
2728203	NM_005862.3(STAG1):c.1026+2T>C	STAG1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3629946	NM_005862.3(STAG1):c.1433A>T (p.His478Leu)	STAG1	Likely pathogenic	criteria provided, single submitter
4293910	NM_005862.3(STAG1):c.568C>T (p.Gln190Ter)	STAG1	Likely pathogenic	criteria provided, single submitter
4294021	NM_005862.3(STAG1):c.1574_1575dup (p.Ile526fs)	STAG1	Likely pathogenic	criteria provided, single submitter
4818998	NM_005862.3(STAG1):c.1744-2A>G	STAG1	Likely pathogenic	criteria provided, single submitter
523186	NM_005862.3(STAG1):c.2009_2012del (p.Asn670fs)	STAG1	Likely pathogenic	criteria provided, single submitter
559649	NM_005862.3(STAG1):c.3261del (p.Lys1087fs)	STAG1	Likely pathogenic	no assertion criteria provided
633008	NM_005862.3(STAG1):c.2557dup (p.Glu853fs)	STAG1	Likely pathogenic	criteria provided, single submitter
1028435	NM_005862.3(STAG1):c.42_44dup (p.Asn14_Glu15insAsp)	STAG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1098685	NM_005862.3(STAG1):c.1056A>T (p.Lys352Asn)	STAG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679663	NM_005862.3(STAG1):c.1189G>C (p.Val397Leu)	STAG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 1 · 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
PMEPA1	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 47	5
STAG1	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 47	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STAG1	Orphanet:502434	STAG1-related intellectual disability-facial dysmorphism-gastroesophageal reflux syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STAG1	HGNC:11354	ENSG00000118007	Q8WVM7	Cohesin subunit SA-1	gencc,clinvar
PMEPA1	HGNC:14107	ENSG00000124225	Q969W9	Protein TMEPAI	gencc,clinvar
AMOTL2	HGNC:17812	ENSG00000114019	Q9Y2J4	Angiomotin-like protein 2	clinvar
IL20RB	HGNC:6004	ENSG00000174564	Q6UXL0	Interleukin-20 receptor subunit beta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STAG1	Cohesin subunit SA-1	Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication.
PMEPA1	Protein TMEPAI	Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression.
AMOTL2	Angiomotin-like protein 2	Regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites.
IL20RB	Interleukin-20 receptor subunit beta	The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · 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
Antibody/Immunoglobulin	1	7.3×	0.260
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STAG1	Other/Unknown	no		STAG, ARM-type_fold, SCD
PMEPA1	Other/Unknown	no		TMEPAI/LRAD4
AMOTL2	Other/Unknown	no		Angiomotin, Angiomotin_C, Angiomotin-like
IL20RB	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, Interferon/interleukin_rcp_dom

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	2
calcaneal tendon	1
parotid gland	1
ascending aorta	1
thoracic aorta	1
visceral pleura	1
amniotic fluid	1
mammary duct	1
lower esophagus mucosa	1
skin of abdomen	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STAG1	293	ubiquitous	marker	calcaneal tendon, parotid gland, sural nerve
PMEPA1	277	ubiquitous	marker	visceral pleura, ascending aorta, thoracic aorta
AMOTL2	289	ubiquitous	marker	amniotic fluid, sural nerve, mammary duct
IL20RB	180	broad	marker	upper arm skin, lower esophagus mucosa, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PMEPA1	2,193
STAG1	2,058
AMOTL2	1,986
IL20RB	1,083

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STAG1	Q8WVM7	20
IL20RB	Q6UXL0	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AMOTL2	Q9Y2J4	67.35
PMEPA1	Q969W9	57.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitotic Telophase/Cytokinesis	1	356.9×	0.035	STAG1
Cohesin Loading onto Chromatin	1	285.5×	0.035	STAG1
Establishment of Sister Chromatid Cohesion	1	259.6×	0.035	STAG1
Signaling by Hippo	1	135.9×	0.044	AMOTL2
Interleukin-20 family signaling	1	105.7×	0.044	IL20RB
Downregulation of TGF-beta receptor signaling	1	102.0×	0.044	PMEPA1
Meiosis	1	71.4×	0.054	STAG1
Reproduction	1	47.6×	0.058	STAG1
S Phase	1	45.3×	0.058	STAG1
SUMO E3 ligases SUMOylate target proteins	1	44.6×	0.058	STAG1
SUMOylation	1	40.8×	0.058	STAG1
SUMOylation of DNA damage response and repair proteins	1	36.6×	0.058	STAG1
Meiotic synapsis	1	35.2×	0.058	STAG1
ESR-mediated signaling	1	32.1×	0.059	STAG1
Signaling by Nuclear Receptors	1	25.5×	0.065	STAG1
Mitotic Metaphase and Anaphase	1	24.2×	0.065	STAG1
Mitotic Anaphase	1	24.2×	0.065	STAG1
Resolution of Sister Chromatid Cohesion	1	21.6×	0.068	STAG1
Estrogen-dependent gene expression	1	18.9×	0.070	STAG1
Signal Transduction	2	5.1×	0.070	STAG1, AMOTL2
Mitotic Prometaphase	1	17.3×	0.073	STAG1
M Phase	1	16.5×	0.073	STAG1
Separation of Sister Chromatids	1	15.2×	0.075	STAG1
Cell Cycle, Mitotic	1	12.1×	0.091	STAG1
Cell Cycle	1	9.0×	0.115	STAG1
Post-translational protein modification	1	4.8×	0.200	STAG1
Metabolism of proteins	1	3.1×	0.286	STAG1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
CD8-positive, alpha-beta T cell homeostasis	1	4213.0×	0.004	IL20RB
negative regulation of type IV hypersensitivity	1	2106.5×	0.004	IL20RB
immune response-inhibiting signal transduction	1	2106.5×	0.004	IL20RB
establishment of cell polarity involved in ameboidal cell migration	1	1404.3×	0.005	AMOTL2
establishment of mitotic sister chromatid cohesion	1	601.9×	0.009	STAG1
positive regulation of protein localization	1	351.1×	0.013	AMOTL2
endothelial cell morphogenesis	1	263.3×	0.014	AMOTL2
inflammatory response to antigenic stimulus	1	234.1×	0.014	IL20RB
sister chromatid cohesion	1	191.5×	0.014	STAG1
hippo signaling	1	183.2×	0.014	AMOTL2
androgen receptor signaling pathway	1	175.5×	0.014	PMEPA1
negative regulation of SMAD protein signal transduction	1	150.5×	0.014	PMEPA1
negative regulation of interleukin-2 production	1	145.3×	0.014	IL20RB
positive regulation of interleukin-4 production	1	140.4×	0.014	IL20RB
homeostasis of number of cells within a tissue	1	110.9×	0.016	IL20RB
positive regulation of interleukin-10 production	1	100.3×	0.016	IL20RB
negative regulation of type II interferon production	1	95.8×	0.016	IL20RB
T cell proliferation	1	95.8×	0.016	IL20RB
mitotic spindle assembly	1	86.0×	0.017	STAG1
negative regulation of T cell proliferation	1	82.6×	0.017	IL20RB
negative regulation of transforming growth factor beta receptor signaling pathway	1	43.4×	0.030	PMEPA1
regulation of cell migration	1	39.4×	0.032	AMOTL2
cytokine-mediated signaling pathway	1	32.7×	0.037	IL20RB
Wnt signaling pathway	1	24.9×	0.046	AMOTL2
actin cytoskeleton organization	1	19.8×	0.056	AMOTL2
angiogenesis	1	15.6×	0.067	AMOTL2
cell division	1	11.5×	0.087	STAG1
negative regulation of transcription by RNA polymerase II	1	4.4×	0.207	AMOTL2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STAG1	0	0
PMEPA1	0	0
AMOTL2	0	0
IL20RB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	1	IL20RB
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	STAG1, PMEPA1, AMOTL2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STAG1	0	—
PMEPA1	0	—
AMOTL2	0	—
IL20RB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.