SMARCB1
Chr 22SWI/SNF related BAF chromatin remodeling complex subunit B1
Also known as: BAF47, CSS3, INI-1, INI1, MRD15, PPP1R144, RDT, RTPS1
The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
Definitive — sufficient evidence for diagnostic panels
2 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
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene — mechanism propensity
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.
References
ClinVar Variant Classifications
487 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 | 23 | 2 | 3 | 0 | 28 |
Likely Pathogenic | 11 | 4 | 3 | 0 | 18 |
VUS | 5 | 209 | 28 | 4 | 246 |
Likely Benign | 1 | 5 | 64 | 105 | 175 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 3 | |||
| Total | 40 | 220 | 100 | 109 | 472 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →4 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap SMARCB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
SMARCB1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Tazemetostat+Nivo/Ipi in INI1-Neg/SMARCA4-Def Tumors
ACTIVE NOT RECRUITINGNatural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors
RECRUITINGPhase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies
RECRUITINGPhase II Trial of Sacituzumab Tirumotecan in Patients With SMARCB1-Deficient Renal Medullary Carcinoma
NOT YET RECRUITINGTiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient 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 RECRUITINGEfficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.
RECRUITINGInduction Chemotherapy and Tazemetostat for Locally Advanced SMARCB1-deficient Sinonasal Carcinoma
NOT YET RECRUITINGFeasibility of Using Bortezomib With or Without Chemotherapy in Patients With Atypical Teratoid/Rhabdoid Tumors
ACTIVE NOT RECRUITINGIxazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools