SMARCB1

Chr 22AD

SWI/SNF related BAF chromatin remodeling complex subunit B1

Also known as: BAF47, CSS3, INI-1, INI1, MRD15, PPP1R144, RDT, RTPS1

NCBI Gene: 6598 ENSG00000099956 UniProt: Q12824 OMIM: 601607

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Rhabdoid tumor predisposition syndrome 1}MIM #609322

{Schwannomatosis-1, susceptibility to}MIM #162091

Coffin-Siris syndrome 3MIM #614608

Rhabdoid tumors, somaticMIM #609322

UniProtSchwannomatosis 1

Clinical highlights

Gene-disease validity (ClinGen)

rhabdoid tumor predisposition syndrome 1 · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

284

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.22

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — SMARCB1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.22LOEUF

pLI 0.997

Z-score 4.10

OE 0.05 (0.01–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.60Z-score

OE missense 0.33 (0.27–0.40)

74 obs / 226.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.05 (0.01–0.22)

0≤0.351.4

Missense OE?0.33 (0.27–0.40)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 21.6Missense obs/exp: 74 / 226.5Syn Z: -0.35

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — SMARCB1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Atypical Teratoid Rhabdoid TumorINI1 (SMARCB1)-Deficient Primary CNS Malignant TumorsSMARCA4-deficient Primary CNS Malignant Tumors

Tazemetostat+Nivo/Ipi in INI1-Neg/SMARCA4-Def Tumors

ACTIVE NOT RECRUITING

NCT05407441Phase PHASE1, PHASE2Susan Chi, MDStarted 2023-08-10

TazemetostatNivolumabIpilimumab

Solid Tumor MalignanciesClear Cell Endometrial CarcinomaOvarian Cancer

Efficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.

RECRUITING

NCT07303387Phase PHASE2Gustave Roussy, Cancer Campus, Grand ParisStarted 2026-03-05

Valemetostat Tosylate

Atypical Teratoid/Rhabdoid Tumors (AT/RTs)Central Nervous System (CNS) Tumors

Feasibility of Using Bortezomib With or Without Chemotherapy in Patients With Atypical Teratoid/Rhabdoid Tumors

ACTIVE NOT RECRUITING

NCT06853080Phase PHASE2Taipei Medical UniversityStarted 2020-12-02

Bortezomib

Sinonasal Carcinoma

Induction Chemotherapy and Tazemetostat for Locally Advanced SMARCB1-deficient Sinonasal Carcinoma

NOT YET RECRUITING

NCT05151588Phase PHASE2Dr. Victor H.F. LeeStarted 2023-09-01

DocetaxelCis Platinum5-FU

Advanced Malignant Solid NeoplasmAnn Arbor Stage III Non-Hodgkin LymphomaAnn Arbor Stage IV Non-Hodgkin Lymphoma

Targeted 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 RECRUITING

NCT03155620Phase PHASE2National Cancer Institute (NCI)Started 2017-07-31

Biopsy ProcedureBiospecimen CollectionBone Marrow Aspiration and Biopsy

SMARCB1-Deficient MalignanciesEpithelioid SarcomaRenal Medullary Carcinoma

Phase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies

ACTIVE NOT RECRUITING

NCT06444880Phase PHASE2M.D. Anderson Cancer CenterStarted 2024-10-09

UbamatamabCemiplimab

Atypical Teratoid/Rhabdoid TumorEpithelioid SarcomaKidney Medullary Carcinoma

Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors

ACTIVE NOT RECRUITING

NCT05286801Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2022-11-17