Intellectual disability, autosomal dominant 15

Summary

Intellectual disability, autosomal dominant 15 (MONDO:0013820) is a disease caused by SMARCB1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: SMARCB1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 15
Mondo ID	MONDO:0013820
OMIM	614608
DOID	DOID:0070045
UMLS	C3553248
MedGen	766162
GARD	0015821
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 15 · COFFIN-SIRIS syndrome 3 · Coffin-Siris syndrome caused by mutation in SMARCB1 · CSS3 · intellectual disability, autosomal dominant 15 · intellectual disability, autosomal dominant type 15 · mental retardation, autosomal dominant 15 · mental retardation, autosomal dominant type 15 · MRD15 · SMARCB1 Coffin-Siris syndrome · SMARCB1-related BAFopathy

Data availability: 41 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 15

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 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

41 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 12 conflicting classifications of pathogenicity, 6 likely pathogenic, 5 pathogenic/likely pathogenic, 2 pathogenic, 1 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
212263	NM_003073.5(SMARCB1):c.1087A>G (p.Lys363Glu)	SMARCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265393	NM_003073.5(SMARCB1):c.1096C>T (p.Arg366Cys)	SMARCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30201	NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del)	SMARCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
30203	NM_003073.5(SMARCB1):c.1130G>A (p.Arg377His)	SMARCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
3336915	NM_003073.5(SMARCB1):c.363-2_363-1del	SMARCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372511	NM_003073.5(SMARCB1):c.1121G>A (p.Arg374Gln)	SMARCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
88893	NM_003073.5(SMARCB1):c.110G>A (p.Arg37His)	SMARCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1012324	NM_003073.5(SMARCB1):c.1084_1086del (p.Glu362del)	SMARCB1	Likely pathogenic	criteria provided, single submitter
1029505	NM_003073.5(SMARCB1):c.812G>A (p.Gly271Glu)	SMARCB1	Likely pathogenic	criteria provided, single submitter
1343154	NM_003073.5(SMARCB1):c.1096C>G (p.Arg366Gly)	SMARCB1	Likely pathogenic	criteria provided, single submitter
3893254	NM_003073.5(SMARCB1):c.1118G>A (p.Arg373Lys)	SMARCB1	Likely pathogenic	criteria provided, single submitter
3897791	NM_003073.5(SMARCB1):c.1096C>A (p.Arg366Ser)	SMARCB1	Likely pathogenic	criteria provided, single submitter
438304	NM_003073.5(SMARCB1):c.602G>A (p.Arg201Gln)	SMARCB1	Likely pathogenic	no assertion criteria provided
135257	NM_003073.5(SMARCB1):c.1A>G (p.Met1Val)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1478236	NM_003073.5(SMARCB1):c.620A>G (p.Asn207Ser)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340912	NM_003073.5(SMARCB1):c.607G>A (p.Ala203Thr)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340913	NM_003073.5(SMARCB1):c.628+13C>T	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
532963	NM_003073.5(SMARCB1):c.1066_1067del (p.Leu356fs)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
532971	NM_003073.5(SMARCB1):c.1118+6C>G	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
559897	NM_003073.5(SMARCB1):c.1070C>G (p.Thr357Arg)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
561114	NM_003073.5(SMARCB1):c.1089G>T (p.Lys363Asn)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
580688	NM_003073.5(SMARCB1):c.790A>G (p.Ile264Val)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
633561	NM_003073.5(SMARCB1):c.1120C>T (p.Arg374Trp)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
839989	NM_003073.5(SMARCB1):c.736G>A (p.Glu246Lys)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
950963	NM_003073.5(SMARCB1):c.1118+4C>G	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1213705	NC_000022.11:g.23774226_23859697dup	DERL3	Uncertain significance	criteria provided, single submitter
1029504	NM_003073.5(SMARCB1):c.487A>G (p.Thr163Ala)	SMARCB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1045351	NM_003073.5(SMARCB1):c.11T>C (p.Met4Thr)	SMARCB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342400	NM_003073.5(SMARCB1):c.628+1487A>G	SMARCB1	Uncertain significance	criteria provided, single submitter
1407743	NM_003073.5(SMARCB1):c.710T>G (p.Ile237Ser)	SMARCB1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 6 · 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
SMARCB1	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 15	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCB1	Orphanet:1465	Coffin-Siris syndrome
SMARCB1	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCB1	Orphanet:2495	Meningioma
SMARCB1	Orphanet:263662	Familial multiple meningioma
SMARCB1	Orphanet:93921	Full schwannomatosis
SMARCB1	Orphanet:99966	Atypical teratoid rhabdoid tumor

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	gencc,clinvar
DERL3	HGNC:14236	ENSG00000099958	Q96Q80	Derlin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.
DERL3	Derlin-3	Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal glycoproteins, but not that of misfolded nonglycoproteins.

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)
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd
DERL3	Other/Unknown	no		DER1, Rhomboid-like_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
embryo	1
ganglionic eminence	1
bone marrow cell	1
duodenum	1
tonsil	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate
DERL3	135	ubiquitous	marker	bone marrow cell, duodenum, tonsil

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCB1	5,083
DERL3	1,156

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCB1	Q12824	17

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DERL3	Q96Q80	84.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 2 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
Formation of the canonical BAF (cBAF) complex	1	317.2×	0.024	SMARCB1
Formation of the polybromo-BAF (pBAF) complex	1	317.2×	0.024	SMARCB1
Formation of the embryonic stem cell BAF (esBAF) complex	1	300.5×	0.024	SMARCB1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	228.4×	0.024	SMARCB1
Regulation of endogenous retroelements	1	184.2×	0.024	SMARCB1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	150.3×	0.024	SMARCB1
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.024	SMARCB1
Defective CFTR causes cystic fibrosis	1	109.8×	0.024	DERL3
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	1	96.8×	0.024	DERL3
MITF-M-dependent gene expression	1	90.6×	0.024	SMARCB1
RMTs methylate histone arginines	1	73.2×	0.025	SMARCB1
Transcriptional regulation by RUNX1	1	73.2×	0.025	SMARCB1
ABC-family protein mediated transport	1	60.7×	0.026	DERL3
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	58.9×	0.026	SMARCB1
MITF-M-regulated melanocyte development	1	57.1×	0.026	SMARCB1
Chromatin organization	1	40.8×	0.034	SMARCB1
Chromatin modifying enzymes	1	36.1×	0.034	SMARCB1
Epigenetic regulation of gene expression	1	35.7×	0.034	SMARCB1
RNA Polymerase II Transcription	1	11.3×	0.101	SMARCB1
Gene expression (Transcription)	1	8.9×	0.120	SMARCB1
Generic Transcription Pathway	1	7.5×	0.134	SMARCB1
Developmental Biology	1	7.2×	0.134	SMARCB1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
single stranded viral RNA replication via double stranded DNA intermediate	1	8426.0×	0.003	SMARCB1
positive regulation of glucose mediated signaling pathway	1	2808.7×	0.005	SMARCB1
RNA polymerase I preinitiation complex assembly	1	1685.2×	0.006	SMARCB1
DNA integration	1	1053.2×	0.006	SMARCB1
negative regulation of retrograde protein transport, ER to cytosol	1	936.2×	0.006	DERL3
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	766.0×	0.006	SMARCB1
hepatocyte differentiation	1	601.9×	0.007	SMARCB1
host-mediated activation of viral transcription	1	443.5×	0.008	SMARCB1
nucleosome disassembly	1	401.2×	0.008	SMARCB1
obsolete protein N-linked glycosylation via asparagine	1	337.0×	0.008	DERL3
regulation of G0 to G1 transition	1	337.0×	0.008	SMARCB1
regulation of nucleotide-excision repair	1	300.9×	0.008	SMARCB1
blastocyst hatching	1	271.8×	0.008	SMARCB1
regulation of mitotic metaphase/anaphase transition	1	247.8×	0.008	SMARCB1
positive regulation of T cell differentiation	1	227.7×	0.008	SMARCB1
transcription initiation-coupled chromatin remodeling	1	191.5×	0.009	SMARCB1
positive regulation of myoblast differentiation	1	183.2×	0.009	SMARCB1
positive regulation of stem cell population maintenance	1	172.0×	0.009	SMARCB1
positive regulation of double-strand break repair	1	172.0×	0.009	SMARCB1
regulation of G1/S transition of mitotic cell cycle	1	153.2×	0.009	SMARCB1
endoplasmic reticulum unfolded protein response	1	147.8×	0.009	DERL3
positive regulation of cell differentiation	1	133.8×	0.009	SMARCB1
ERAD pathway	1	90.6×	0.013	DERL3
chromatin remodeling	1	36.5×	0.032	SMARCB1
nervous system development	1	23.0×	0.048	SMARCB1
negative regulation of cell population proliferation	1	21.1×	0.051	SMARCB1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.135	SMARCB1
regulation of transcription by RNA polymerase II	1	5.8×	0.164	SMARCB1

Therapeutics

Drug target analysis

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

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
SMARCB1	0	0
DERL3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCB1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SMARCB1, DERL3

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)
SMARCB1	7	—
DERL3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.