SMARCE1

Chr 17AD

SWI/SNF related BAF chromatin remodeling complex subunit E1

Also known as: BAF57, CSS5

NCBI Gene: 6605ENSG00000073584UniProt: Q969G3

The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Meningioma, familial, susceptibility to}MIM #607174
AD
Coffin-Siris syndrome 5MIM #616938
AD
200
ClinVar variants
10
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SMARCE1
🧬
Gene-Disease Validity (ClinGen)
familial meningioma · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
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
10 Pathogenic / Likely Pathogenic· 117 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.19LOEUF
pLI 0.999
Z-score 4.44
OE 0.04 (0.01–0.19)
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.
2.74Z-score
OE missense 0.51 (0.44–0.59)
123 obs / 243.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.04 (0.01–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.44–0.59)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 1 / 24.9Missense obs/exp: 123 / 243.3Syn Z: 0.28

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic7
VUS117
Likely Benign71
Benign1
Conflicting1
3
Pathogenic
7
Likely Pathogenic
117
VUS
71
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
0
0
3
Likely Pathogenic
5
2
0
0
7
VUS
4
101
9
3
117
Likely Benign
0
4
31
36
71
Benign
0
0
1
0
1
Conflicting
—1
Total111084139200

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SMARCE1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SMARCE1-related Coffin Siris

strong
ADUndeterminedAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

SMARCE1-related meningioma, familial

definitive
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Cancer
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Meningioma, familial, susceptibility to}

MIM #607174

Molecular basis of disorder known

Autosomal dominant

Coffin-Siris syndrome 5

MIM #616938

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — SMARCE1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.
Vasko A et al.·Genes (Basel)
2021
Targeted next-generation sequencing for differential diagnosis of neurofibromatosis type 2, schwannomatosis, and meningiomatosis.
Louvrier C et al.·Neuro Oncol
2018
European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection.
Sahm F et al.·Neuro Oncol
2025Review
Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals.
Schmetz A et al.·Hum Genet
2024
A heritable form of SMARCE1-related meningiomas with important implications for follow-up and family screening.
Gerkes EH et al.·Neurogenetics
2016Review
SMARCE1, a rare cause of Coffin-Siris Syndrome: Clinical description of three additional cases.
Zarate YA et al.·Am J Med Genet A
2016Review
An update on the CNS manifestations of neurofibromatosis type 2.
Coy S et al.·Acta Neuropathol
2020Review
SWI/SNF deficient central nervous system neoplasms.
Cai C·Semin Diagn Pathol
2021Review
SMARCE1 mutation screening in classification of clear cell meningiomas.
Smith MJ et al.·Histopathology
2017
Germline SMARCE1 mutations predispose to both spinal and cranial clear cell meningiomas.
Smith MJ et al.·J Pathol
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools