SMARCC1-associated developmental dysgenesis syndrome

Summary

SMARCC1-associated developmental dysgenesis syndrome (MONDO:0700123) is a disease caused by SMARCC1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SMARCC1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	SMARCC1-associated developmental dysgenesis syndrome
Mondo ID	MONDO:0700123
Is cancer (heuristic)	no

Also known as: SMARCC1-related BAFopathy

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › BAFopathy › SMARCC1-associated developmental dysgenesis syndrome

Related subtypes (14): Coffin-Siris syndrome 1, Baraitser-Winter syndrome 1, intellectual disability-sparse hair-brachydactyly syndrome, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, Coffin-Siris syndrome 5, Dias-Logan syndrome, Coffin-Siris syndrome 8, intellectual developmental disorder with severe speech and ambulation defects, Coffin-Siris syndrome 6, intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities, ACTL6A-related BAFopathy, PBRM1-related BAFopathy

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

4 retrieved; paginated sample, class counts are floors:

4 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177321	NM_003074.4(SMARCC1):c.3013C>T (p.Gln1005Ter)	SMARCC1	Uncertain significance	criteria provided, single submitter
1177322	NM_003074.4(SMARCC1):c.2464del (p.Ser822fs)	SMARCC1	Uncertain significance	criteria provided, single submitter
1177323	NM_003074.4:c.402-?_646+?del	SMARCC1	Uncertain significance	criteria provided, single submitter
1177324	NM_003074.4:c.402-?_483+?del	SMARCC1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
SMARCC1	Definitive	Autosomal dominant	SMARCC1-associated developmental dysgenesis syndrome	4

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCC1	HGNC:11104	ENSG00000173473	Q92922	SWI/SNF complex subunit SMARCC1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCC1	SWI/SNF complex subunit SMARCC1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCC1	Transcription factor	no		Chromo/chromo_shadow_dom, SANT/Myb, SWIRM

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
embryo	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCC1	290	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCC1	3,999

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCC1	Q92922	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 1 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×	0.008	SMARCC1
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.008	SMARCC1
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.008	SMARCC1
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.008	SMARCC1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.009	SMARCC1
Regulation of endogenous retroelements	1	368.4×	0.009	SMARCC1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.009	SMARCC1
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.009	SMARCC1
MITF-M-dependent gene expression	1	181.3×	0.012	SMARCC1
RMTs methylate histone arginines	1	146.4×	0.012	SMARCC1
Transcriptional regulation by RUNX1	1	146.4×	0.012	SMARCC1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.013	SMARCC1
MITF-M-regulated melanocyte development	1	114.2×	0.013	SMARCC1
Chromatin organization	1	81.6×	0.018	SMARCC1
Chromatin modifying enzymes	1	72.3×	0.018	SMARCC1
Epigenetic regulation of gene expression	1	71.4×	0.018	SMARCC1
RNA Polymerase II Transcription	1	22.5×	0.052	SMARCC1
Gene expression (Transcription)	1	17.8×	0.062	SMARCC1
Generic Transcription Pathway	1	15.1×	0.069	SMARCC1
Developmental Biology	1	14.5×	0.069	SMARCC1

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
prostate gland development	1	1404.3×	0.006	SMARCC1
nucleosome disassembly	1	802.5×	0.006	SMARCC1
regulation of G0 to G1 transition	1	674.1×	0.006	SMARCC1
regulation of nucleotide-excision repair	1	601.9×	0.006	SMARCC1
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.006	SMARCC1
positive regulation of T cell differentiation	1	455.5×	0.006	SMARCC1
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	1	401.2×	0.006	SMARCC1
positive regulation of myoblast differentiation	1	366.4×	0.006	SMARCC1
positive regulation of stem cell population maintenance	1	343.9×	0.006	SMARCC1
positive regulation of double-strand break repair	1	343.9×	0.006	SMARCC1
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.006	SMARCC1
negative regulation of cell differentiation	1	285.6×	0.006	SMARCC1
positive regulation of cell differentiation	1	267.5×	0.006	SMARCC1
insulin receptor signaling pathway	1	221.7×	0.007	SMARCC1
animal organ morphogenesis	1	191.5×	0.007	SMARCC1
chromatin remodeling	1	73.0×	0.018	SMARCC1
nervous system development	1	45.9×	0.027	SMARCC1
positive regulation of cell population proliferation	1	33.6×	0.035	SMARCC1
positive regulation of DNA-templated transcription	1	27.9×	0.040	SMARCC1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	SMARCC1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SMARCC1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMARCC1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SMARCC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCC1	8	Binding:8

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

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	SMARCC1

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	SMARCC1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.