SMARCB1
Chr 22ADSWI/SNF related BAF chromatin remodeling complex subunit B1
Also known as: BAF47, CSS3, INI-1, INI1, MRD15, PPP1R144, RDT, RTPS1
The protein relieves repressive chromatin structures to allow transcriptional machinery access to target genes and functions as a tumor suppressor. Loss-of-function mutations cause autosomal dominant rhabdoid tumor predisposition syndrome 1, Coffin-Siris syndrome 3, and susceptibility to schwannomatosis-1. The pathogenic mechanism involves haploinsufficiency, as the gene is highly intolerant to loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
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 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
100 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 | 3 | 0 | 0 | 0 | 3 |
Likely Pathogenic | 0 | 2 | 1 | 0 | 3 |
VUS | 1 | 52 | 4 | 1 | 58 |
Likely Benign | 0 | 1 | 0 | 25 | 26 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 4 | 55 | 5 | 26 | 91 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SMARCB1 · 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
Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors
RECRUITINGEfficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.
RECRUITINGIxazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer
ACTIVE NOT 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 RECRUITINGPhase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies
RECRUITINGFeasibility of Using Bortezomib With or Without Chemotherapy in Patients With Atypical Teratoid/Rhabdoid Tumors
ACTIVE NOT RECRUITINGTiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
ACTIVE NOT RECRUITINGPhase II Trial of Sacituzumab Tirumotecan in Patients With SMARCB1-Deficient Renal Medullary Carcinoma
NOT YET RECRUITINGInduction Chemotherapy and Tazemetostat for Locally Advanced SMARCB1-deficient Sinonasal Carcinoma
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools