SMARCA4
Chr 19SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4
Also known as: BAF190, BAF190A, BRG1, CSS4, MRD16, OTSC12, RTPS2, SNF2
The protein functions as an ATPase and helicase component of the SWI/SNF chromatin remodeling complex, altering chromatin structure to enable transcriptional activation of normally repressed genes. Heterozygous loss-of-function mutations cause autosomal dominant Coffin-Siris syndrome 4 and rhabdoid tumor predisposition syndrome 2. The protein is intolerant to loss-of-function variants, with pathogenicity resulting from haploinsufficiency of the chromatin remodeling function.
Definitive — sufficient evidence for diagnostic panels
3 total gene-disease associations curated
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 15 | 1 | 0 | 0 | 16 |
Likely Pathogenic | 14 | 2 | 0 | 0 | 16 |
VUS | 1 | 178 | 11 | 2 | 192 |
Likely Benign | 1 | 2 | 60 | 58 | 121 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 31 | 183 | 71 | 60 | 346 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SMARCA4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Genetically Risk-Stratified Venetoclax, Ibrutinib, Rituximab (± Navitoclax) in Relapsed/Refractory Mantle Cell Lymphoma
ACTIVE NOT RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGNatural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors
RECRUITINGA Phase II Study of QL1706 and Platinum-Based Chemotherapy in Patients With SMARCA4-Deficient, Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
NOT YET RECRUITINGEfficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.
RECRUITINGStudy of Nivolumab and Ipilimumab in Children and Young Adults With INI1-Negative Cancers
ACTIVE NOT RECRUITINGEfficacy and Safety Analysis of First-Line ABCP Therapy in Advanced SMARCA4-Mutated NSCLC
NOT YET RECRUITINGFirst-in-Human Study of PLX-61639 in Locally Advanced or Metastatic Solid Tumors
RECRUITINGSMARCA4/2 Inhibitor for POU2F3-Positive SCLC
NOT YET RECRUITINGOnline Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGTazemetostat+Nivo/Ipi in INI1-Neg/SMARCA4-Def Tumors
ACTIVE NOT RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools