SMARCA4
Chr 19ADSWI/SNF related BAF chromatin remodeling complex subunit ATPase 4
Also known as: BAF190, BAF190A, BRG1, CSS4, MRD16, OTSC12, RTPS2, SNF2
The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
3 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
ClinVar Variant Classifications
542 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 | 13 | 1 | 15 | 0 | 29 |
Likely Pathogenic | 15 | 3 | 2 | 0 | 20 |
VUS | 2 | 268 | 29 | 2 | 301 |
Likely Benign | 1 | 3 | 59 | 124 | 187 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 5 | |||
| Total | 31 | 275 | 105 | 126 | 542 |
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.
Gene2Phenotype Curations
SMARCA4-related Coffin Siris
definitiveSMARCA4-related rhabdoid tumor predisposition syndrome
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGA Phase II Study of Anlotinib and Platinum-Based Chemotherapy in Patients With SMARCA4-Deficient, Locally Advanced or Metastatic Lung Cancer.
NOT YET RECRUITINGA Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors
RECRUITINGPhase II Study of Tazemetostat in Solid Tumors Harboring an ARID1A Mutation
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 RECRUITINGGenetically Risk-Stratified Venetoclax, Ibrutinib, Rituximab (± Navitoclax) in Relapsed/Refractory Mantle Cell Lymphoma
ACTIVE NOT RECRUITINGNatural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors
RECRUITINGEfficacy and Safety Analysis of First-Line ABCP Therapy in Advanced SMARCA4-Mutated NSCLC
NOT YET RECRUITINGFeasibility of Using Bortezomib With or Without Chemotherapy in Patients With Atypical Teratoid/Rhabdoid Tumors
ACTIVE NOT RECRUITINGTazemetostat+Nivo/Ipi in INI1-Neg/SMARCA4-Def Tumors
RECRUITINGEfficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.
NOT YET RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGExternal Resources
Links to major genomics databases and tools