SNAI1

Chr 20

snail family transcriptional repressor 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

Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration (PubMed:10655587, PubMed:15647282, PubMed:20389281, PubMed:20562920, PubMed:21952048, PubMed:25827072). Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription (PubMed:10655587, PubMed:20389281, PubMed:20562920). The N-terminal SNAG domain competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (in vitro) (PubMed:20389281, PubMed:21300290, PubMed:23721412). During EMT, involved with LOXL2 in negatively regulating pericentromeric heterochromatin transcription (PubMed:16096638). SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (By similarity). Associates with EGR1 and SP1 to mediate tetradecanoyl phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3 (PubMed:20121949). In addition, may also activate the CDKN2B promoter by itself (PubMed:20121949)

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease · ADLimitednot 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

160

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.68

LOEUF

Mechanism· predicted