SMARCB1

Chr 22AD

SWI/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]

Primary Disease Associations & Inheritance

{Rhabdoid tumor predisposition syndrome 1}MIM #609322
AD
{Schwannomatosis-1, susceptibility to}MIM #162091
AD
Coffin-Siris syndrome 3MIM #614608
AD
Rhabdoid tumors, somaticMIM #609322
UniProtSchwannomatosis 1
1501
ClinVar variants
52
Pathogenic / LP
1.00
pLI score· haploinsufficient
10
Active trials
Clinical SummarySMARCB1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 248 VUS of 1501 total submissions
💊
Clinical Trials
10 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.22LOEUF
pLI 0.997
Z-score 4.10
OE 0.05 (0.010.22)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.60Z-score
OE missense 0.33 (0.270.40)
74 obs / 226.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.010.22)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.33 (0.270.40)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
01.21.6
LoF obs/exp: 1 / 21.6Missense obs/exp: 74 / 226.5Syn Z: -0.35

ClinVar Variant Classifications

1501 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic21
VUS248
Likely Benign181
Benign2
Conflicting2
31
Pathogenic
21
Likely Pathogenic
248
VUS
181
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
2
13
0
31
Likely Pathogenic
12
5
4
0
21
VUS
3
201
41
3
248
Likely Benign
1
5
64
111
181
Benign
0
0
2
0
2
Conflicting
2
Total32213124114485

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.

Gene2Phenotype Curations

SMARCB1-related Coffin-Siris syndrome

definitive
ADUndeterminedAltered Gene Product Structure
Dev. DisordersSkin
G2P ↗
missense variantinframe deletioninframe insertion

SMARCB1-related schwannomatosis

definitive
ADLoss Of FunctionAbsent Gene Product
Cancer
G2P ↗

SMARCB1-related rhabdoid tumor predisposition syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

{Rhabdoid tumor predisposition syndrome 1}

MIM #609322

Molecular basis of disorder known

Autosomal dominant

{Schwannomatosis-1, susceptibility to}

MIM #162091

Molecular basis of disorder known

Autosomal dominant

Coffin-Siris syndrome 3

MIM #614608

Molecular basis of disorder known

Autosomal dominant

Rhabdoid tumors, somatic

MIM #609322

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
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
Phase IISacituzumabTirumotecan

Phase II Trial of Sacituzumab Tirumotecan in Patients With SMARCB1-Deficient Renal Medullary Carcinoma

NOT YET RECRUITING
NCT07438626Phase PHASE2M.D. Anderson Cancer CenterStarted 2026-06-01
Sacituzumab tirumotecan
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
Atypical Teratoid Rhabdoid TumorINI1 (SMARCB1)-Deficient Primary CNS Malignant TumorsSMARCA4-deficient Primary CNS Malignant Tumors

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

RECRUITING
NCT05407441Phase PHASE1, PHASE2Susan Chi, MDStarted 2023-08-10
TazemetostatNivolumabIpilimumab
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
AtezolizumabBiospecimen CollectionComputed Tomography
Metastatic Kidney Medullary CarcinomaMetastatic Renal Cell CarcinomaSMARCB1 Negative

Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

ACTIVE NOT RECRUITING
NCT03587662Phase PHASE2M.D. Anderson Cancer CenterStarted 2018-08-17
DoxorubicinDoxorubicin HydrochlorideGemcitabine
Malignant Solid TumorsOther Neoplasms Solid TumorsPediatric Solid Tumor

Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors

RECRUITING
NCT03739827National Cancer Institute (NCI)Started 2019-01-28
Solid Tumor MalignanciesClear Cell Endometrial CarcinomaOvarian Cancer

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

NOT YET RECRUITING
NCT07303387Phase PHASE2Gustave Roussy, Cancer Campus, Grand ParisStarted 2026-02-28
Valemetostat Tosylate
SMARCB1-Deficient Malignancies

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

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