Intellectual disability, autosomal dominant 16

Summary

Intellectual disability, autosomal dominant 16 (MONDO:0013821) is a disease caused by SMARCA4 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: SMARCA4 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 698

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 16
Mondo ID	MONDO:0013821
OMIM	614609
DOID	DOID:0070046
UMLS	C3553249
MedGen	766163
GARD	0015822
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 16 · COFFIN-SIRIS syndrome 4 · Coffin-Siris syndrome caused by mutation in SMARCA4 · CSS4 · intellectual disability, autosomal dominant 16 · intellectual disability, autosomal dominant type 16 · mental retardation, autosomal dominant 16 · mental retardation, autosomal dominant type 16 · MRD16 · SMARCA4 Coffin-Siris syndrome · SMARCA4-related BAFopathy

Data availability: 698 ClinVar variants · 3 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 16

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 14, intellectual disability, autosomal dominant 15, 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

600 retrieved; paginated sample, class counts are floors:

267 conflicting classifications of pathogenicity, 184 uncertain significance, 81 benign/likely benign, 24 likely benign, 19 likely pathogenic, 11 benign, 9 pathogenic, 5 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3892517	NC_000023.11:g.11088932_11088935del	HCCS-DT	Pathogenic	criteria provided, single submitter
1342164	NM_003072.5(SMARCA4):c.2475G>T (p.Trp825Cys)	SMARCA4	Pathogenic	criteria provided, single submitter
1698824	NM_003072.5(SMARCA4):c.2683C>T (p.Gln895Ter)	SMARCA4	Pathogenic	criteria provided, single submitter
1762032	NM_003072.5(SMARCA4):c.810dup (p.Gly271fs)	SMARCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
212246	NM_003072.5(SMARCA4):c.2936G>A (p.Arg979Gln)	SMARCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30342	NM_003072.5(SMARCA4):c.1633AAG[1] (p.Lys546del)	SMARCA4	Pathogenic	criteria provided, single submitter
30344	NM_003072.5(SMARCA4):c.2653C>T (p.Arg885Cys)	SMARCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30345	NM_003072.5(SMARCA4):c.2761C>T (p.Leu921Phe)	SMARCA4	Pathogenic	no assertion criteria provided
30346	NM_003072.5(SMARCA4):c.3032T>C (p.Met1011Thr)	SMARCA4	Pathogenic	no assertion criteria provided
30347	NM_003072.5(SMARCA4):c.3469C>G (p.Arg1157Gly)	SMARCA4	Pathogenic	no assertion criteria provided
403671	NM_003072.5(SMARCA4):c.2851G>A (p.Gly951Arg)	SMARCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
436813	NM_003072.5(SMARCA4):c.3127C>T (p.Arg1043Trp)	SMARCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449452	NM_003072.5(SMARCA4):c.3608G>A (p.Arg1203His)	SMARCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4819789	NM_003072.5(SMARCA4):c.3470G>A (p.Arg1157Gln)	SMARCA4	Pathogenic	criteria provided, single submitter
1177356	NM_003072.5(SMARCA4):c.1646G>T (p.Arg549Leu)	SMARCA4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1177367	NM_003072.5(SMARCA4):c.2738C>T (p.Pro913Leu)	SMARCA4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
126361	NM_003072.5(SMARCA4):c.3922C>T (p.Arg1308Trp)	SMARCA4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1294427	NM_003072.5(SMARCA4):c.3476G>C (p.Gly1159Ala)	SMARCA4	Likely pathogenic	criteria provided, single submitter
1325852	NM_003072.5(SMARCA4):c.1462G>A (p.Glu488Lys)	SMARCA4	Likely pathogenic	criteria provided, single submitter
1338815	NM_003072.5(SMARCA4):c.2453G>A (p.Trp818Ter)	SMARCA4	Likely pathogenic	criteria provided, single submitter
1691273	NM_003072.5(SMARCA4):c.3139A>C (p.Asn1047His)	SMARCA4	Likely pathogenic	no assertion criteria provided
1691499	NM_003072.5(SMARCA4):c.2525G>A (p.Arg842Gln)	SMARCA4	Likely pathogenic	criteria provided, single submitter
1698715	NM_003072.5(SMARCA4):c.2747A>G (p.Asn916Ser)	SMARCA4	Likely pathogenic	criteria provided, single submitter
1698826	NM_003072.5(SMARCA4):c.1427T>G (p.Leu476Arg)	SMARCA4	Likely pathogenic	criteria provided, single submitter
1802555	NM_003072.5(SMARCA4):c.3068A>G (p.Glu1023Gly)	SMARCA4	Likely pathogenic	criteria provided, single submitter
2433576	NM_003072.5(SMARCA4):c.2506-2A>G	SMARCA4	Likely pathogenic	criteria provided, single submitter
2444058	NM_003072.5(SMARCA4):c.1352G>T (p.Arg451Leu)	SMARCA4	Likely pathogenic	criteria provided, single submitter
2663773	NM_003072.5(SMARCA4):c.3712T>G (p.Ser1238Ala)	SMARCA4	Likely pathogenic	criteria provided, single submitter
3062125	NM_003072.5(SMARCA4):c.2678T>G (p.Leu893Arg)	SMARCA4	Likely pathogenic	criteria provided, single submitter
3778711	NM_003072.5(SMARCA4):c.2831A>C (p.Asn944Thr)	SMARCA4	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 4 · 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
SMARCA4	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 16	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	gencc,clinvar
HCCS-DT	HGNC:55698	ENSG00000234129		HCCS divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
HCCS-DT	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cervix squamous epithelium	1
cortical plate	1
ganglionic eminence	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
HCCS-DT	128		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCA4	8,138
HCCS-DT	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCA4	P51532	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the non-canonical BAF (ncBAF) complex	1	671.8×	0.012	SMARCA4
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.012	SMARCA4
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.012	SMARCA4
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.012	SMARCA4
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.012	SMARCA4
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.012	SMARCA4
Regulation of endogenous retroelements	1	368.4×	0.012	SMARCA4
Interleukin-7 signaling	1	317.2×	0.012	SMARCA4
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.012	SMARCA4
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.012	SMARCA4
MITF-M-dependent gene expression	1	181.3×	0.014	SMARCA4
RMTs methylate histone arginines	1	146.4×	0.014	SMARCA4
Transcriptional regulation by RUNX1	1	146.4×	0.014	SMARCA4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.014	SMARCA4
Formation of the beta-catenin:TCF transactivating complex	1	120.2×	0.014	SMARCA4
Negative Regulation of CDH1 Gene Transcription	1	120.2×	0.014	SMARCA4
TCF dependent signaling in response to WNT	1	117.7×	0.014	SMARCA4
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.014	SMARCA4
MITF-M-regulated melanocyte development	1	114.2×	0.014	SMARCA4
Signaling by WNT	1	112.0×	0.014	SMARCA4
Chromatin organization	1	81.6×	0.019	SMARCA4
Chromatin modifying enzymes	1	72.3×	0.019	SMARCA4
Epigenetic regulation of gene expression	1	71.4×	0.019	SMARCA4
Signaling by Interleukins	1	64.2×	0.021	SMARCA4
Nervous system development	1	42.9×	0.030	SMARCA4
Cytokine Signaling in Immune system	1	40.8×	0.030	SMARCA4
RNA Polymerase II Transcription	1	22.5×	0.053	SMARCA4
Gene expression (Transcription)	1	17.8×	0.064	SMARCA4
Generic Transcription Pathway	1	15.1×	0.073	SMARCA4
Developmental Biology	1	14.5×	0.074	SMARCA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 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 glucose mediated signaling pathway	1	5617.3×	0.005	SMARCA4
RNA polymerase I preinitiation complex assembly	1	3370.4×	0.005	SMARCA4
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	1532.0×	0.005	SMARCA4
positive regulation of signal transduction by p53 class mediator	1	1203.7×	0.005	SMARCA4
neural retina development	1	936.2×	0.005	SMARCA4
negative regulation of androgen receptor signaling pathway	1	936.2×	0.005	SMARCA4
host-mediated activation of viral transcription	1	887.0×	0.005	SMARCA4
nucleosome disassembly	1	802.5×	0.005	SMARCA4
regulation of G0 to G1 transition	1	674.1×	0.005	SMARCA4
regulation of nucleotide-excision repair	1	601.9×	0.005	SMARCA4
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.005	SMARCA4
positive regulation of T cell differentiation	1	455.5×	0.005	SMARCA4
positive regulation of Wnt signaling pathway	1	383.0×	0.005	SMARCA4
transcription initiation-coupled chromatin remodeling	1	383.0×	0.005	SMARCA4
positive regulation of myoblast differentiation	1	366.4×	0.005	SMARCA4
positive regulation of stem cell population maintenance	1	343.9×	0.005	SMARCA4
positive regulation of double-strand break repair	1	343.9×	0.005	SMARCA4
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.006	SMARCA4
positive regulation of miRNA transcription	1	290.6×	0.006	SMARCA4
negative regulation of cell differentiation	1	285.6×	0.006	SMARCA4
positive regulation of cell differentiation	1	267.5×	0.006	SMARCA4
heterochromatin formation	1	255.3×	0.006	SMARCA4
positive regulation of cold-induced thermogenesis	1	163.6×	0.009	SMARCA4
negative regulation of cell growth	1	144.0×	0.009	SMARCA4
chromatin remodeling	1	73.0×	0.018	SMARCA4
nervous system development	1	45.9×	0.027	SMARCA4
positive regulation of cell population proliferation	1	33.6×	0.035	SMARCA4
negative regulation of DNA-templated transcription	1	31.6×	0.036	SMARCA4
positive regulation of DNA-templated transcription	1	27.9×	0.039	SMARCA4
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	SMARCA4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMARCA4	2	2
HCCS-DT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SMARCA4
CAMIBIRSTAT	2	SMARCA4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCA4	230	Binding:207, ADMET:12, Functional:11

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SMARCA4	230

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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	SMARCA4
CAMIBIRSTAT	2	SMARCA4

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	SMARCA4
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HCCS-DT

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HCCS-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.