SNAI3

Chr 16

snail family transcriptional repressor 3

Also known as: SMUC, SNAIL3, ZNF293, Zfp293

NCBI Gene: 333929 ENSG00000185669 UniProt: Q3KNW1 OMIM: 612741

The SNAI3 protein is a transcriptional repressor that inhibits myoblast differentiation by binding to E-box sequences and repressing downstream myogenic genes. Mutations in SNAI3 cause autosomal recessive myopathy with structural abnormalities, corneal dystrophy and hearing loss, a multisystem disorder affecting muscle, eye, and auditory systems. This gene shows tolerance to loss-of-function variants in the population, suggesting the pathogenic variants may have specific functional consequences.

OMIM ResearchSummary from RefSeq, UniProt

SNAI3 is a member of the SNAIL gene family, named for the Drosophila snail gene, which plays roles in mesodermal formation during embryogenesis (Katoh and Katoh, 2003 [PubMed 12579345]).[supplied by OMIM, Apr 2009]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.14

Clinical Summary— SNAI3

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

55 VUS of 62 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.013

Z-score 1.31

OE 0.50 (0.25–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.87Z-score

OE missense 1.17 (1.05–1.31)

229 obs / 195.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.50 (0.25–1.14)

0≤0.351.4

Missense OE?1.17 (1.05–1.31)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 4 / 8.0Missense obs/exp: 229 / 195.0Syn Z: -1.43

This gene — mechanism propensity

0.75top 25%

GOF

0.6930th %ile

LOF

0.4037th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

62 submitted variants in ClinVar

ClinVar

Classification Summary

VUS55

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	55	55
Likely Benign	3	3
Benign	0	0
Total	58	58

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

View in ClinVar →

65 pathogenic / likely-pathogenic (of 91) ClinVar copy-number / structural variants overlap SNAI3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →