SNAI1
protein-codingsnail family transcriptional repressor 1, the group of SNAG transcriptional repressors|Zinc fingers C2H2-type
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005453
Submitter: ClinGen
*SNAI1* was first reported in relation to autosomal dominant congenital heart disease in 2018 (Shi et al., PMID: 30448225). 2 variants (missense) that have been reported in 2 probands in 2 publications (PMIDs: 30448225, 32368696) are included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (expression-level data; PMID: 28880281). Expression-level data in chick and mouse embryos shows expression in the posterior heart poles and left and right sinus horns. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 10/01/24 (SOP Version 11).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SNAI1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005985.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 22 | 1 | 23 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 22 | 0 | 1 | 23 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005976.2 | 3 | MANE Select | |
| Ensembl | ENSP00000244050.2 | 3 | MANE Select | |
| Ensembl | ENSP00000755335.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| snai1a | Danio rerio | Structure: postcranial axial skeleton Quality: ossified abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adherens junction - Homo sapiens (human)
- Neural Crest Differentiation
- Mesodermal Commitment Pathway
- Kit receptor signaling pathway
- TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition
Biological Process
- negative regulation of transcription by RNA polymerase II
- osteoblast differentiation
- mesoderm formation
- epithelial to mesenchymal transition
- aortic valve morphogenesis
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- protein binding
- kinase binding
Cellular Component
- nucleus
- nucleoplasm
- pericentric heterochromatin
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000244050
- Coding exons
- 3
- Length
- 5888
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125743
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.31 | 112 | 159 | 0.706 | 0.00000915 | 1687 |
| Missense (PolyPhen) | 24 | 60.103 | 0.39932 | 591 | ||
| Synonymous | -0.657 | 78 | 71.0 | 1.10 | 0.00000423 | 559 |
| Loss of Function | 2.30 | 3 | 11.4 | 0.264 | 6.39e-7 | 106 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. 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. During EMT, involved with LOXL2 in negatively regulating pericentromeric heterochromatin transcription (By similarity). 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. In addition, may also activate the CDKN2B promoter by itself. {ECO:0000250|UniProtKB:Q02085, ECO:0000269|PubMed:10655587, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21952048}.;
Recessive Scores
- pRec
- 0.331
Intolerance Scores
- LoFtool
- 0.232
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 60.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.959
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |