SNAI1

Chr 20

snail family transcriptional repressor 1

Also known as: SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1

The protein encoded by this gene is a zinc finger transcriptional repressor that induces epithelial-to-mesenchymal transition and is critical for mesoderm formation during embryonic development by repressing genes like E-cadherin through recruitment of histone demethylases. Mutations cause Waardenburg syndrome type 3, an autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary abnormalities including heterochromia and white forelock, and upper limb defects. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.68), and the condition typically presents in early childhood with the characteristic pigmentary and hearing features.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
109
Pubs (1 yr)
9
P/LP submissions
0%
P/LP missense
0.68
LOEUF
DN
Mechanism· predicted
Clinical SummarySNAI1
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 23 VUS of 38 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.218
Z-score 2.30
OE 0.26 (0.120.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.31Z-score
OE missense 0.71 (0.600.83)
112 obs / 158.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.120.68)
00.351.4
Missense OE0.71 (0.600.83)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 3 / 11.4Missense obs/exp: 112 / 158.6Syn Z: -0.66
DN
0.7131th %ile
GOF
0.5660th %ile
LOF
0.50top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

38 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS23
Benign1
7
Pathogenic
2
Likely Pathogenic
23
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
21
2
0
23
Likely Benign
0
0
0
0
0
Benign
0
1
0
0
1
Total02211033

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

View in ClinVar →

Protein Context — Lollipop Plot

SNAI1 · 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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