SNAI1

Chr 20

snail family transcriptional repressor 1

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

NCBI Gene: 6615 ENSG00000124216 UniProt: O95863 OMIM: 604238

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.

OMIM ResearchSummary from RefSeq, UniProt

The Drosophila embryonic protein snail is a zinc finger transcriptional repressor which downregulates the expression of ectodermal genes within the mesoderm. The nuclear protein encoded by this gene is structurally similar to the Drosophila snail protein, and is also thought to be critical for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Limited · congenital heart disease · AD · ClinGen 2024

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

169

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.218

Z-score 2.30

OE 0.26 (0.12–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.31Z-score

OE missense 0.71 (0.60–0.83)

112 obs / 158.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.12–0.68)

0≤0.351.4

Missense OE?0.71 (0.60–0.83)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 3 / 11.4Missense obs/exp: 112 / 158.6Syn Z: -0.66

Background carrier burden — how many people carry a rare variant somewhere in SNAI1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 380

302 rare PASS variants

Rare truncating (LoF)

1 in 15,000

26 rare PASS variants

Rare synonymous (reference)

1 in 490

173 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SNAI1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 330	1 in 10,000
South Asian	~43k	1 in 470	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 630	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,300	none seen
Admixed American	~22k	1 in 340	≈ 1 in 22,000
African / African American	~21k	1 in 300	none seen
East Asian	~20k	1 in 280	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 500	none seen
Middle Eastern	~2,884	1 in 320	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓