SMARCE1

Chr 17AD

SWI/SNF related BAF chromatin remodeling complex subunit E1

Also known as: BAF57, CSS5

The encoded protein is a component of the SWI/SNF chromatin remodeling complex that binds to 4-way junction DNA and enables transcriptional activation of genes normally repressed by chromatin. Loss-of-function mutations cause Coffin-Siris syndrome 5, a neurodevelopmental disorder characterized by intellectual disability, distinctive facial features, and hypoplastic fifth fingernails and toenails, following an autosomal dominant inheritance pattern. Mutations also predispose to familial meningioma.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.192 OMIM phenotypes
Clinical SummarySMARCE1
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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.
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ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 168 VUS of 300 total submissions
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GeneReview available — SMARCE1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 0.999
Z-score 4.44
OE 0.04 (0.010.19)
Highly constrained

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

Missense Constraint
2.74Z-score
OE missense 0.51 (0.440.59)
123 obs / 243.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.010.19)
00.351.4
Missense OE0.51 (0.440.59)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 1 / 24.9Missense obs/exp: 123 / 243.3Syn Z: 0.28
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSMARCE1-related Coffin SirisOTHERAD
definitiveSMARCE1-related meningioma, familialLOFAD
DN
0.3793th %ile
GOF
0.3690th %ile
LOF
0.75top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-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.

LOFprediction above median · 1 literature citation · 68% of P/LP variants are LoF · LOEUF 0.19
DN1 literature citation

Literature Evidence

DNMutations in SMARCB1, SMARCA4, and SMARCE1 are expected to exert dominant-negative or gain-of-function effects, whereas those in ARID1A are expected to exert loss-of-function effects.PMID:25168959
LOFLoss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas.PMID:23377182

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

300 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic6
VUS168
Likely Benign92
Benign3
Conflicting2
16
Pathogenic
6
Likely Pathogenic
168
VUS
92
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
4
2
0
16
Likely Pathogenic
5
1
0
0
6
VUS
4
150
11
3
168
Likely Benign
0
4
40
48
92
Benign
0
0
3
0
3
Conflicting
2
Total191595651287

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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