Intellectual disability, autosomal dominant 14

Summary

Intellectual disability, autosomal dominant 14 (MONDO:0013819) is a disease caused by ARID1A (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: ARID1A (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 221

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 14
Mondo ID	MONDO:0013819
OMIM	614607
DOID	DOID:0070044
UMLS	C3553247
MedGen	766161
GARD	0015820
Is cancer (heuristic)	no

Also known as: ARID1A Coffin-Siris syndrome · ARID1A-related BAFopathy · autosomal dominant intellectual disability 14 · Coffin-Siris syndrome caused by mutation in ARID1A · CSS2 · intellectual disability, autosomal dominant 14 · intellectual disability, autosomal dominant type 14 · mental retardation, autosomal dominant 14 · mental retardation, autosomal dominant type 14 · MRD14

Data availability: 221 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant 14

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

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

221 retrieved; paginated sample, class counts are floors:

80 uncertain significance, 37 pathogenic, 36 benign/likely benign, 27 likely pathogenic, 17 conflicting classifications of pathogenicity, 15 benign, 4 pathogenic/likely pathogenic, 4 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1120179	NM_006015.6(ARID1A):c.5940_6000del (p.Val1982fs)	ARID1A	Pathogenic	criteria provided, single submitter
1177329	NM_006015.6(ARID1A):c.166C>T (p.Gln56Ter)	ARID1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1182296	NM_006015.6(ARID1A):c.3230C>A (p.Ala1077Glu)	ARID1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323396	NM_006015.6(ARID1A):c.1850C>A (p.Ser617Ter)	ARID1A	Pathogenic	criteria provided, single submitter
1323404	NM_006015.6(ARID1A):c.2122C>T (p.Gln708Ter)	ARID1A	Pathogenic	criteria provided, single submitter
1675353	NM_006015.6(ARID1A):c.1642C>T (p.Gln548Ter)	ARID1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1699033	NM_006015.6(ARID1A):c.3058A>T (p.Arg1020Trp)	ARID1A	Pathogenic	criteria provided, single submitter
210259	NM_006015.6(ARID1A):c.394del (p.Val132fs)	ARID1A	Pathogenic	criteria provided, single submitter
225842	NM_006015.6(ARID1A):c.5965C>T (p.Arg1989Ter)	ARID1A	Pathogenic	criteria provided, single submitter
225843	NM_006015.6(ARID1A):c.1113del (p.Gln372fs)	ARID1A	Pathogenic	no assertion criteria provided
225844	NM_006015.6(ARID1A):c.3679G>T (p.Glu1227Ter)	ARID1A	Pathogenic	no assertion criteria provided
2412701	NM_006015.6(ARID1A):c.4087C>T (p.Gln1363Ter)	ARID1A	Pathogenic	criteria provided, single submitter
2442347	NM_006015.6(ARID1A):c.1015del (p.Ala339fs)	ARID1A	Pathogenic	criteria provided, multiple submitters, no conflicts
2500289	NM_006015.6(ARID1A):c.3287A>G (p.Tyr1096Cys)	ARID1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2576602	NM_006015.6(ARID1A):c.284del (p.Gly95fs)	ARID1A	Pathogenic	criteria provided, single submitter
2582256	NM_006015.6(ARID1A):c.5566C>T (p.Gln1856Ter)	ARID1A	Pathogenic	criteria provided, single submitter
30292	NM_006015.6(ARID1A):c.31_56del (p.Ser11fs)	ARID1A	Pathogenic	criteria provided, multiple submitters, no conflicts
30293	NM_006015.6(ARID1A):c.2758C>T (p.Gln920Ter)	ARID1A	Pathogenic	no assertion criteria provided
30294	NM_006015.6(ARID1A):c.4003C>T (p.Arg1335Ter)	ARID1A	Pathogenic	criteria provided, single submitter
3076211	NM_006015.6(ARID1A):c.476dup (p.Ala160fs)	ARID1A	Pathogenic	criteria provided, single submitter
3220888	NM_006015.6(ARID1A):c.5229_5230dup (p.Leu1744fs)	ARID1A	Pathogenic	criteria provided, single submitter
3235938	NM_006015.6(ARID1A):c.1507C>T (p.Gln503Ter)	ARID1A	Pathogenic	criteria provided, single submitter
3237157	NM_006015.6(ARID1A):c.4582C>T (p.Arg1528Ter)	ARID1A	Pathogenic	criteria provided, single submitter
3255192	NM_006015.6(ARID1A):c.961C>T (p.Gln321Ter)	ARID1A	Pathogenic	criteria provided, single submitter
3897837	NM_006015.6(ARID1A):c.3092del (p.Thr1031fs)	ARID1A	Pathogenic	criteria provided, single submitter
3906955	NM_006015.6(ARID1A):c.5259_5262dup (p.Ser1755delinsValTer)	ARID1A	Pathogenic	criteria provided, single submitter
434335	NM_006015.6(ARID1A):c.921_940del (p.Tyr308fs)	ARID1A	Pathogenic	criteria provided, single submitter
434343	NM_006015.6(ARID1A):c.5164C>T (p.Arg1722Ter)	ARID1A	Pathogenic	criteria provided, single submitter
452118	NM_006015.6(ARID1A):c.3033G>T (p.Leu1011Phe)	ARID1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4759294	NM_006015.6(ARID1A):c.1970_1971del (p.Leu657fs)	ARID1A	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 5 · 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
ARID1A	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 14	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARID1A	Orphanet:1465	Coffin-Siris syndrome
ACTN4	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
HR	Orphanet:444	Marie Unna hereditary hypotrichosis
HR	Orphanet:701	Alopecia universalis
HR	Orphanet:86819	Atrichia with papular lesions

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	gencc,clinvar
ACTN4	HGNC:166	ENSG00000130402	O43707	Alpha-actinin-4	clinvar
HR	HGNC:5172	ENSG00000168453	O43593	Lysine-specific demethylase hairless	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARID1A	AT-rich interactive domain-containing protein 1A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
ACTN4	Alpha-actinin-4	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
HR	Lysine-specific demethylase hairless	Histone demethylase that specifically demethylates both mono- and dimethylated ‘Lys-9’ of histone H3.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
ACTN4	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
HR	Enzyme (other)	yes	1.14.11.65	JmjC_dom, LSDs-like

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bone marrow cell	1
embryo	1
ventricular zone	1
popliteal artery	1
smooth muscle tissue	1
tibial artery	1
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
ACTN4	145	ubiquitous	marker	popliteal artery, tibial artery, smooth muscle tissue
HR	235	broad	marker	skin of abdomen, skin of leg, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARID1A	3,476
ACTN4	3,303
HR	559

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARID1A	O14497	7
ACTN4	O43707	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HR	O43593	55.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Positive Regulation of CDH1 Gene Transcription	1	475.8×	0.022	ARID1A
Formation of the canonical BAF (cBAF) complex	1	317.2×	0.022	ARID1A
Formation of the embryonic stem cell BAF (esBAF) complex	1	300.5×	0.022	ARID1A
Nephrin family interactions	1	237.9×	0.022	ACTN4
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	228.4×	0.022	ARID1A
Regulation of endogenous retroelements	1	184.2×	0.023	ARID1A
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	150.3×	0.023	ARID1A
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.023	ARID1A
MITF-M-dependent gene expression	1	90.6×	0.028	ARID1A
Response to elevated platelet cytosolic Ca2+	1	81.6×	0.028	ACTN4
RMTs methylate histone arginines	1	73.2×	0.028	ARID1A
Transcriptional regulation by RUNX1	1	73.2×	0.028	ARID1A
Cell-Cell communication	1	68.8×	0.028	ACTN4
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	58.9×	0.029	ARID1A
MITF-M-regulated melanocyte development	1	57.1×	0.029	ARID1A
Platelet activation, signaling and aggregation	1	52.9×	0.029	ACTN4
Platelet degranulation	1	43.9×	0.033	ACTN4
Chromatin organization	1	40.8×	0.034	ARID1A
Chromatin modifying enzymes	1	36.1×	0.035	ARID1A
Epigenetic regulation of gene expression	1	35.7×	0.035	ARID1A
Hemostasis	1	18.0×	0.065	ACTN4
RNA Polymerase II Transcription	1	11.3×	0.099	ARID1A
Gene expression (Transcription)	1	8.9×	0.118	ARID1A
Generic Transcription Pathway	1	7.5×	0.133	ARID1A
Developmental Biology	1	7.2×	0.134	ARID1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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 sodium:proton antiporter activity	1	1872.4×	0.015	ACTN4
vesicle transport along actin filament	1	802.5×	0.015	ACTN4
peroxisome proliferator activated receptor signaling pathway	1	510.7×	0.015	ACTN4
negative regulation of substrate adhesion-dependent cell spreading	1	374.5×	0.015	ACTN4
muscle cell development	1	312.1×	0.015	ACTN4
nucleosome disassembly	1	267.5×	0.015	ARID1A
regulation of G0 to G1 transition	1	224.7×	0.015	ARID1A
retinoic acid receptor signaling pathway	1	216.1×	0.015	ACTN4
regulation of nucleotide-excision repair	1	200.6×	0.015	ARID1A
regulation of mitotic metaphase/anaphase transition	1	165.2×	0.016	ARID1A
positive regulation of T cell differentiation	1	151.8×	0.016	ARID1A
transcription initiation-coupled chromatin remodeling	1	127.7×	0.016	ARID1A
positive regulation of myoblast differentiation	1	122.1×	0.016	ARID1A
positive regulation of stem cell population maintenance	1	114.6×	0.016	ARID1A
positive regulation of double-strand break repair	1	114.6×	0.016	ARID1A
tumor necrosis factor-mediated signaling pathway	1	110.1×	0.016	ACTN4
regulation of G1/S transition of mitotic cell cycle	1	102.1×	0.016	ARID1A
positive regulation of cell differentiation	1	89.2×	0.017	ARID1A
positive regulation of non-canonical NF-kappaB signal transduction	1	85.1×	0.017	ACTN4
regulation of transcription by RNA polymerase II	2	7.8×	0.029	ARID1A, HR
regulation of apoptotic process	1	27.8×	0.047	ACTN4
actin cytoskeleton organization	1	26.4×	0.048	ACTN4
chromatin remodeling	1	24.3×	0.049	ARID1A
positive regulation of cell migration	1	20.6×	0.056	ACTN4
nervous system development	1	15.3×	0.072	ARID1A
protein transport	1	14.6×	0.072	ACTN4
positive regulation of DNA-templated transcription	1	9.3×	0.107	ARID1A
positive regulation of transcription by RNA polymerase II	1	5.0×	0.188	ACTN4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACTN4	1	2
ARID1A	0	0
HR	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ACTN4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ACTN4	7	Binding:7
ARID1A	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HR	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	ACTN4

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	1	ACTN4
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	HR
E	Difficult family or no structure, no drug	1	ARID1A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ARID1A	6	—
HR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.