SNAI1

Summary

SNAI1 (snail family transcriptional repressor 1, HGNC:11128) is a protein-coding gene on chromosome 20q13.13, encoding Zinc finger protein SNAI1 (O95863). Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration.

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.

Source: NCBI Gene 6615 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 27 total
• Transcription factor: yes — 103 downstream targets (CollecTRI)
• MANE Select transcript: NM_005985

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11128
Approved symbol	SNAI1
Name	snail family transcriptional repressor 1
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	SNA, SLUGH2, SNAH, SNAIL1, SNAIL
Ensembl gene	ENSG00000124216
Ensembl biotype	protein_coding
OMIM	604238
Entrez	6615

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000244050

RefSeq mRNA: 1 — MANE Select: NM_005985 NM_005985

CCDS: CCDS13423

Canonical transcript exons

ENST00000244050 — 3 exons

Exon	Start	End
ENSE00000845600	49983824	49984351
ENSE00000845601	49987872	49988886
ENSE00001172559	49982980	49983141

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 86.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8892 / max 623.1279, expressed in 1494 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185196	11.8892	1494

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
omental fat pad	UBERON:0010414	86.39	gold quality
peritoneum	UBERON:0002358	86.31	gold quality
gall bladder	UBERON:0002110	85.33	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.03	gold quality
left uterine tube	UBERON:0001303	83.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.12	gold quality
right lobe of thyroid gland	UBERON:0001119	83.01	gold quality
left lobe of thyroid gland	UBERON:0001120	82.29	gold quality
ascending aorta	UBERON:0001496	81.85	gold quality
thoracic aorta	UBERON:0001515	81.49	gold quality
upper lobe of left lung	UBERON:0008952	81.45	gold quality
right lung	UBERON:0002167	81.38	gold quality
left coronary artery	UBERON:0001626	81.01	gold quality
right atrium auricular region	UBERON:0006631	80.74	gold quality
right coronary artery	UBERON:0001625	80.73	gold quality
upper lobe of lung	UBERON:0008948	80.54	gold quality
thyroid gland	UBERON:0002046	80.23	gold quality
coronary artery	UBERON:0001621	79.75	gold quality
descending thoracic aorta	UBERON:0002345	79.74	gold quality
cardiac atrium	UBERON:0002081	79.73	gold quality
left adrenal gland cortex	UBERON:0035825	79.36	gold quality
left adrenal gland	UBERON:0001234	79.18	gold quality
right adrenal gland	UBERON:0001233	78.65	gold quality
adrenal cortex	UBERON:0001235	77.58	gold quality
aorta	UBERON:0000947	77.51	gold quality
diaphragm	UBERON:0001103	77.37	gold quality
cervix squamous epithelium	UBERON:0006922	77.30	gold quality
right adrenal gland cortex	UBERON:0035827	77.05	gold quality
mucosa of stomach	UBERON:0001199	76.30	gold quality
adrenal gland	UBERON:0002369	76.14	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.68

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

103 targets.

Target	Regulation
ACAN	Unknown
ACTA2
ADIPOQ
ADRA1D
AKT1
AKT2
BRCA1	Repression
CCL2
CCL5
CCN6
CD44
CDH1	Repression
CDH17
CDH2	Unknown
CDH3
CDH5	Unknown
CDKN1A	Unknown
CDKN2B
CEL
CLDN1
CLDN3	Repression
CLDN7	Repression
COL2A1	Unknown
CTSG
CXADR	Repression
CXCL8
CYP19A1
DLG1	Unknown
DLST
DSG2

JASPAR motifs

Motif	Name	Family
MA1558.1	SNAI1	More than 3 adjacent zinc fingers
MA1558.2	SNAI1	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:26170144

Upstream regulators (CollecTRI, top): ACVR1, AR, BCL11B, CREB1, CUX1, EGR1, ENG, ERG, ESR1, ESRRA, ETV4, FOSL1, FOXC1, FOXM1, GLI1, HIF1A, HMGA2, HOXA10, ID2, IKZF1, JAG1, LBX1, MTA1, MTA3, MYC, NCOA3, NFKB1, NOTCH1, PARP1, PBX1, RBPJ, RELA, SATB2, SMAD2, SMAD3, SMAD4, SNAI1, TCF3, TFAP4, TGFB1

miRNA regulators (miRDB)

75 targeting SNAI1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-22-3P	99.93	68.13	917

Literature-anchored findings (GeneRIF, showing 40)

• Snail expression inversely correlates with the grade of differentiation of the tumours and that it is expressed in all the infiltrating ductal carcinomas (IDC) presenting lymph node metastases that were analysed. (PMID:12082640)
• SNA1 plays a role in repressing E-cadherin and MUC1 in epithelial cells (PMID:12161443)
• Snail is a new inducer of MMP-2 expression which contributes to the increased invasion of squamous cell carcinoma cells (PMID:12632084)
• E-cadherin and claudins/occludin have roles in the regulation of tight junctions during the epithelium-mesenchyme transition, but are repressed by snail (PMID:12668723)
• Hypoxia induces down-regulation of E-cadherin in ovarian carcinoma cells, via up-regulation of the transcriptional repressor SNAIL. (PMID:14507651)
• Snail expression may be induced during hepatocellular cell carcinoma progression; Snail directly represses gene transcription and activates invasion via upregulation of MMP gene family (PMID:15026811)
• Results indicate that Snail is involved in both the direct transcriptional repression of genes and post-transcriptional.These data support the idea that Snail is a transcription factor possessing pleiotropic activities. (PMID:15075229)
• Snail transcription is driven by signaling pathways known to induce epithelial to mesenchymal transition, reinforcing the role of Snail in this proces (PMID:15286702)
• Results suggest that aberrant expression of Snail or Slug may promote tumorigenesis through increased resistance to programmed cell death. (PMID:15314165)
• SNAl1 is regulated by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. (PMID:15448698)
• E-cadherin mRNA expression in synovial sarcoma was associated with reduced Snail expression level (PMID:15467754)
• Data show that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture, and that GSK-3 inhibition stimulates the transcription of Snail. (PMID:15631989)
• Wnt signaling stabilizes Snail and beta-catenin proteins in tandem fashion so as to cooperatively engage transcriptional programs that control an epithelial-mesenchymal transition. (PMID:15647282)
• demonstrated, for the first time, that SNAIL is upregulated in colon cancer, which potentially may have significance in control of metastasis and possibly serve as a target for chemopreventive agents (PMID:15712635)
• Over expression of Smad-interacting protein 1 is associated with ovarian carcinoma aggressiveness (PMID:15742334)
• zinc finger domain functions as a nuclear localization signal, can be transported into the nucleus by importin beta-mediated (PMID:15836774)
• Snail may play a role in recurrence by downregulating E-cadherin and inducing an epithelial-to-mesenchymal transition in breast cancer. (PMID:16169460)
• SNAIL expression in colorectal tumors is associated with downregulation of E-cadherin (CDH1) and vitamin D receptor gene products (PMID:16203744)
• Human cancers that overexpress snail may have a survival advantage to genotoxic and potentially other forms of stress (PMID:16207734)
• The pattern of Snail expression suggests only a minor role of Snail in tumours of the upper gastrointestinal tract. (PMID:16328348)
• Snail is present in activated mesenchymal cells indicating its relevance in the communication between tumor and stroma and suggest that it can promote the conversion of carcinoma cells to stromal cells. (PMID:16568079)
• These findings indicate that Snail upregulation by HGF is mediated via the MAPK/Egr-1 signaling pathway and that both Snail and Egr-1 play a critical role in HGF-induced cell scattering, migration, and invasion. (PMID:16858414)
• These results indicate that NBS1 overexpression induces EMT through the upregulation of Snail expression, and co-expression of NBS1/Snail predicts metastasis in HNSCCs (PMID:16936774)
• VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail (PMID:17060462)
• The identification of a beta-catenin-T-cell factor-regulated Axin2-GSK3beta-Snail1 axis provides new mechanistic insights into cancer-associated epithelial-mesenchymal transition programmes. (PMID:17072303)
• Overexpression of a constitutively activated IGF-IR (CD8-IGF-IR) was sufficient to cause transformation of immortalized human mammary epithelial cells and growth in immunocompromised mice. (PMID:17296734)
• Snail regulates the activity of PRL-3 gene by binding to the promoter of PRL-3 gene in SW480 cells. (PMID:17545014)
• the Snail promoter is constitutively packaged in a poised chromatin structure that can be activated in melanoma cells by a tissue-specific enhancer, which physically contacts the promoter (PMID:17616667)
• Snail1 is involved in renal tubular EMT and TGF-beta1 regulates Snail1 at the transcription and protein degradation levels (PMID:17692821)
• Data show that SNAI1 and SNAI2 are ectopically expressed in thyroid carcinomas, and aberrant expression in mice is associated with papillary carcinoma development. (PMID:17724139)
• Snail and SHH are overexpressed in a large subset of NETs of the ileum. (PMID:17914115)
• RKIP is a novel component of the Snail transcriptional regulatory network important for the progression and metastasis of cancer. (PMID:17952120)
• Snail is associated with lower overall survival of ovarian cancer patients. (PMID:18026186)
• These data are in line with a proposed role for Snail in endometrial tumor progression. (PMID:18043286)
• Analysis of cell lines derived from lymph node metastasis indicates that SNAI1 expression is required for metastatic dissemination. (PMID:18089802)
• These data show that Snail functions as a molecular mediator of TGF-beta1-regulated MMP-9 expression by increasing Ets-1 and thereby contributing to oral cancer progression. (PMID:18234959)
• These results lead to a new hypothesis that Snail and ZEB1 are downstream of CCN6 and play a critical role in CCN6-mediated regulation of E-cadherin in breast cancer. (PMID:18321996)
• A positive feedback stimulation of the Wnt pathway by activation of snail. (PMID:18469861)
• A novel autocrine function for VEGF in breast tumor cells in driving the expression of Snail, a breast tumor progression factor. (PMID:18554584)
• Overexpression of Snail is associated with up-regulation of proinflammatory mediators and inhibits differentiation in oral keratinocytes and thus head and neck squamous cell carcinomas (PMID:18559496)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snai1b	ENSDARG00000046019
danio_rerio	snai1a	ENSDARG00000056995
mus_musculus	Snai1	ENSMUSG00000042821
rattus_norvegicus	Rnf114	ENSRNOG00000060821
caenorhabditis_elegans		WBGENE00019299

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

Zinc finger protein SNAI1 — O95863 (reviewed: O95863)

Alternative names: Protein snail homolog 1

All UniProt accessions (1): O95863

UniProt curated annotations — full annotation on UniProt →

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. 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). During EMT, involved with LOXL2 in negatively regulating pericentromeric heterochromatin transcription. 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. 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.

Subunit / interactions. Interacts (via SNAG domain) with WTIP (via LIM domains). Interacts (via SNAG domain) with LIMD1 (via LIM domains), and AJUBA (via LIM domains). Interacts with LOXL2 and LOXL3. Interacts with EGR1 upon TPA induction. Interacts (via zinc fingers) with KPNB1 and TNPO1; the interactions mediate nuclear import. Interacts (via zinc fingers) with KPNA1; the interaction disrupts the transport complex with KPNB1 and prevents nuclear import increasing SNAI1 degradation in the cytoplasm. Interacts (via zinc fingers) with KPNA2; the interaction, in combination with KPNB1, mediates nuclear import. Interacts with KPNA4; this interaction mediates nuclear import. May interact (via zinc fingers) with IPO7. Interacts (via zinc fingers) with PARP1; the interaction requires SNAI1 to be poly-ADP-ribosylated and non-phosphorylated (active) by GSK3B. Interacts (via SNAG domain) with KDM1A. Interaction with KDM1A is necessary for the down-regulation of dimethylated H3K4 mark and promoter activity of E-cadherin/CDH1, CDN7 and KRT8. Interacts with TP53/p53 and (via zinc fingers) with NOTCH1 (via intracellular domain); the interactions induce SNAI1 degradation via MDM2-mediated ubiquitination and inhibit SNAI1-induced cell invasion. Interacts with MDM2; the interaction promotes SNAI1 ubiquitination.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in a variety of tissues with the highest expression in kidney. Expressed in mesenchymal and epithelial cell lines.

Post-translational modifications. Phosphorylated by GSK3B. Once phosphorylated, it becomes a target for ubiquitination by BTRC, the ECS(SPSB3) or the SCF(FBXO11) complexes. Phosphorylation by CSNK1E, probably at Ser-104, provides the priming site for the subsequent phosphorylation by GSK3B, probably at Ser-100 and Ser-96. Phosphorylation by PAK1 may modulate its transcriptional activity by promoting increased accumulation in the nucleus. Phosphorylation at Ser-11 and Ser-92 positively regulates its functions in induction of EMT and cell survival, respectively. Phosphorylation by LATS2, upon mitotic stress, oncogenic stress or Hippo pathway activation, occurs in the nucleus and promotes nuclear retention and stabilization of total cellular protein level. Ubiquitinated on Lys-98, Lys-137 and Lys-146 by FBXL14 and BTRC leading to degradation. BTRC-triggered ubiquitination requires previous GSK3B-mediated SNAI1 phosphorylation. Ubiquitinated by the SCF(FBXO11) complex; ubiquitination requires previous GSK3B-mediated SNAI1 phosphorylation. Ubiquitinated by the ECS(SPSB3) complex; ubiquitination requires previous GSK3B-mediated SNAI1 phosphorylation. Ubiquitination induced upon interaction with NOTCH1 or TP53/p53 is mediated by MDM2. Ubiquitinated in a FBXL5-dependent manner; preventing interaction with DNA and promoting its degradation. Deubiquitinated by USP37; leading to stabilization. O-GlcNAcylation at Ser-112 is enhanced in hyperglycaemic conditions, it opposes phosphorylation by GSK3B, and stabilizes the protein. ADP-ribosylation by PARP1 increases protein half-life and may be involved in TGFB-induced SNAI1 up-regulation.

Induction. Induced by TPA maximally by 2.5-fold at 4 hours, in HepG2 cells (at protein level).

Similarity. Belongs to the snail C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_005976* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050527

Pfam: PF00096, PF13912

UniProt features (94 total): mutagenesis site 47, modified residue 12, region of interest 7, helix 6, strand 5, zinc finger region 4, cross-link 3, turn 3, sequence variant 2, sequence conflict 2, chain 1, short sequence motif 1, glycosylation site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4QLI	X-RAY DIFFRACTION	1.45
3W5K	X-RAY DIFFRACTION	2.6
8F59	X-RAY DIFFRACTION	2.8
8FJ7	X-RAY DIFFRACTION	2.8
8BOX	X-RAY DIFFRACTION	2.82
8FDV	X-RAY DIFFRACTION	2.95
2Y48	X-RAY DIFFRACTION	3
3ZMT	X-RAY DIFFRACTION	3.1
8ULZ	X-RAY DIFFRACTION	3.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95863-F1	57.97	0.03

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (15): 11, 82, 92, 96, 100, 104, 107, 111, 115, 119, 203, 246, 98, 137, 146

Glycosylation sites (1): 112

Mutagenesis-validated functional residues (47):

Position	Phenotype
2	abolishes repressor activity on e-cadherin/cdh1 promoter and binding to kdm1a.
3	loss of interaction with kdm1a.
4	loss of interaction with kdm1a.
5	loss of interaction with kdm1a.
8	loss of interaction with kdm1a.
9	loss of interaction with kdm1a.
9	does not affect e-cadherin/cdh1 repression; when associated with r-16.
11	abolishes pka phosphorylation. strongly decreases repressor activity on e-cadherin/cdh1 and cldn1 promoters. increases p
16	does not affect e-cadherin repression; when associated with r-9.
92	abolishes ck2 phosphorylation. strongly decreases repressor activity on e-cadherin/cdh1 and cldn1 promoters. increases p
92	does not affect repressor activity on e-cadherin/cdh1 promoter.
96	abolishes recognition and ubiquitination by btrc which increases steady state level and half-life. preferentially locali
98	no change. complete loss of sensitivity to fbxl14- and btrc-triggered degradation and loss of ability to repress e-cadhe
100	lower sensitivity to btrc-triggered degradation and impaired phosphorylation by gsk3b; when associated with a-96. lower
104	increases protein stability, does not affect repressor activity on e-cadherin/cdh1 promoter, preferentially localizes to
107	lower sensitivity to btrc-triggered degradation, impaired phosphorylation by gsk3b and loss of cytoplasmic localization;
107	predominantly localized to the cytoplasm; when associated with e-111; e-115 and e-119.
111	lower sensitivity to btrc-triggered degradation, impaired phosphorylation by gsk3b and loss of cytoplasmic localization;
111	predominantly localized to the cytoplasm; when associated with e-107; e-115 and e-119.
115	lower sensitivity to btrc-triggered degradation, impaired phosphorylation by gsk3b and loss of cytoplasmic localization;
115	predominantly localized to the cytoplasm; when associated with e-107; e-111 and e-119.
119	lower sensitivity to btrc-triggered degradation, impaired phosphorylation by gsk3b and loss of cytoplasmic localization;
119	predominantly localized to the cytoplasm; when associated with e-107; e-111 and e-115.
137	lower sensitivity to fbxl14-triggered degradation. lower sensitivity to fbxl14-triggered degradation; when associated wi
146	lower sensitivity to fbxl14-triggered degradation. lower sensitivity to fbxl14-triggered degradation; when associated wi

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9758919	Epithelial-Mesenchymal Transition (EMT) during gastrulation
R-HSA-9762293	Regulation of CDH11 gene transcription
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-1500931	Cell-Cell communication
R-HSA-162582	Signal Transduction
R-HSA-418990	Adherens junctions interactions
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization
R-HSA-6807070	PTEN Regulation
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9758941	Gastrulation
R-HSA-9759475	Regulation of CDH11 Expression and Function
R-HSA-9759476	Regulation of Homotypic Cell-Cell Adhesion
R-HSA-9764260	Regulation of Expression and Function of Type II Classical Cadherins

MSigDB gene sets: 313 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMIS_MORPHOGENESIS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_APICAL_JUNCTION_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_STEROID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (28): negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), mesoderm formation (GO:0001707), epithelial to mesenchymal transition (GO:0001837), aortic valve morphogenesis (GO:0003180), epithelial to mesenchymal transition involved in endocardial cushion formation (GO:0003198), regulation of DNA-templated transcription (GO:0006355), Notch signaling pathway (GO:0007219), epithelial cell migration (GO:0010631), positive regulation of epithelial to mesenchymal transition (GO:0010718), negative regulation of vitamin D biosynthetic process (GO:0010957), positive regulation of cell migration (GO:0030335), hair follicle morphogenesis (GO:0031069), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), positive regulation of DNA-templated transcription (GO:0045893), roof of mouth development (GO:0060021), canonical Wnt signaling pathway (GO:0060070), cartilage morphogenesis (GO:0060536), trophoblast giant cell differentiation (GO:0060707), negative regulation of cell differentiation involved in embryonic placenta development (GO:0060806), left/right pattern formation (GO:0060972), heterochromatin organization (GO:0070828), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), regulation of bicellular tight junction assembly (GO:2000810), regulation of transcription by RNA polymerase II (GO:0006357), mesoderm development (GO:0007498), negative regulation of DNA-templated transcription (GO:0045892), mesenchymal cell differentiation (GO:0048762)

GO Molecular Function (11): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), kinase binding (GO:0019900), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), pericentric heterochromatin (GO:0005721), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
PTEN Regulation	1
Gastrulation	1
Regulation of CDH11 Expression and Function	1
Regulation of CDH1 Gene Transcription	1
Intracellular signaling by second messengers	1
Cell-cell junction organization	1
Cell junction organization	1
Cell-Cell communication	1
PIP3 activates AKT signaling	1
Signal Transduction	1
Developmental Biology	1
Regulation of Expression and Function of Type II Classical Cadherins	1
Adherens junctions interactions	1
Regulation of Homotypic Cell-Cell Adhesion	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA-templated transcription	2
cell differentiation involved in embryonic placenta development	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
ossification	1
cell differentiation	1
formation of primary germ layer	1
mesoderm morphogenesis	1
mesenchymal cell differentiation	1
aortic valve development	1
heart valve morphogenesis	1
endocardial cushion formation	1
cardiac epithelial to mesenchymal transition	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell surface receptor signaling pathway	1
ameboidal-type cell migration	1
epithelium migration	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
negative regulation of steroid biosynthetic process	1
vitamin D biosynthetic process	1
negative regulation of vitamin metabolic process	1
regulation of vitamin D biosynthetic process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
hair follicle development	1
anatomical structure morphogenesis	1
hair cycle process	1
epidermis morphogenesis	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
negative regulation of signal transduction by p53 class mediator	1
regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

4522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNAI1	SMAD3	P84022	994
SNAI1	HDAC1	Q13547	992
SNAI1	EZH2	Q15910	992
SNAI1	DNMT1	P26358	991
SNAI1	EHMT2	Q96KQ7	991
SNAI1	HDAC2	Q92769	987
SNAI1	KDM1A	O60341	986
SNAI1	TP53	P04637	973
SNAI1	CDH1	P12830	962
SNAI1	LOXL2	Q9Y4K0	962
SNAI1	SMAD4	Q13485	957
SNAI1	CTNNB1	P35222	934
SNAI1	CDH2	P19022	933
SNAI1	SUZ12	Q15022	895
SNAI1	TWIST1	Q15672	894

IntAct

221 interactions, top by confidence:

A	B	Type	Score
SNAI1	KDM1A	psi-mi:“MI:0914”(association)	0.830
KDM1A	SNAI1	psi-mi:“MI:0407”(direct interaction)	0.830
SNAI1	KDM1A	psi-mi:“MI:0915”(physical association)	0.830
KDM1A	SNAI1	psi-mi:“MI:0915”(physical association)	0.830
KDM1A	SNAI1	psi-mi:“MI:0403”(colocalization)	0.830
KDM1A	SNAI1	psi-mi:“MI:0914”(association)	0.830

BioGRID (775): SNAI1 (Two-hybrid), SNAI1 (Two-hybrid), SNAI1 (Two-hybrid), MID2 (Two-hybrid), MTUS2 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), SNAI1 (Reconstituted Complex), SNAI1 (Affinity Capture-Western), SNAI1 (Affinity Capture-Western), AKT1 (Reconstituted Complex), AKT2 (Reconstituted Complex), AKT1 (Affinity Capture-Western), AKT2 (Affinity Capture-Western)

ESM2 similar proteins: A0JPB4, A0PJY2, B0K011, O08876, O15090, O57415, O62651, O70237, O75626, O95863, P19544, P22561, P41183, P49952, P55878, P86413, Q02085, Q08DS3, Q0IHB8, Q0P4W9, Q0VDQ9, Q25C93, Q28G88, Q2TAR3, Q2VWH6, Q32NK7, Q3MHQ4, Q3T135, Q3UH06, Q567J8, Q5T0B9, Q5VTD9, Q5XJQ7, Q60636, Q62255, Q66JF8, Q6AY34, Q6DBW0, Q6NRM0, Q804Q5

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, E9PW05, E9PZZ1, G5EBU4, O15391, O60315, O62836, O75362, O77459, O95863, P08048, P0CS62, P0CS63, P10925, P15822, P17010, P17012, P20662, P22227, P25490, P28166, P31509, P31629, P36197, P52739, P52746, P56270, P56670, P56671, P60319, P80944, Q00899, Q00900

SIGNOR signaling

73 interactions.

A	Effect	B	Mechanism
GSK3B	down-regulates	SNAI1	phosphorylation
PAK1	up-regulates	SNAI1	phosphorylation
PKN1	up-regulates	SNAI1	phosphorylation
CSNK2A1	“up-regulates quantity by stabilization”	SNAI1	phosphorylation
CSNK2A1	up-regulates	SNAI1	phosphorylation
PRKAA1	“up-regulates quantity by stabilization”	SNAI1	phosphorylation
PRKAA1	up-regulates	SNAI1	phosphorylation
PRKD1	“down-regulates activity”	SNAI1	phosphorylation
SFN	down-regulates	SNAI1	relocalization
LATS2	up-regulates	SNAI1	phosphorylation
SNAI1	up-regulates	Epithelial-mesenchymal_transition
SNAI1	“down-regulates quantity”	CDH1	“transcriptional regulation”
SNAI1	“up-regulates quantity by expression”	SERPINE1	“transcriptional regulation”
SNAI1	“up-regulates quantity by expression”	PLAU	“transcriptional regulation”
CREB1	“down-regulates quantity by repression”	SNAI1	“transcriptional regulation”
ESRRA	“down-regulates quantity by repression”	SNAI1	“transcriptional regulation”
SNAI1	“up-regulates activity”	CTBP1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Activity through Methylation	5	56.6×	5e-06
NOTCH1 Intracellular Domain Regulates Transcription	6	29.7×	6e-06
Regulation of PTEN gene transcription	7	26.0×	3e-06
Constitutive Signaling by NOTCH1 PEST Domain Mutants	6	24.6×	1e-05
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	6	24.6×	1e-05
Transcriptional and post-translational regulation of MITF-M expression and activity	5	18.6×	3e-04
Transcriptional regulation of white adipocyte differentiation	6	16.2×	1e-04
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	15.2×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of stem cell population maintenance	5	69.6×	4e-06
cellular response to gamma radiation	5	54.7×	1e-05
canonical NF-kappaB signal transduction	5	33.3×	8e-05
positive regulation of stem cell population maintenance	5	31.3×	8e-05
cellular response to UV	5	26.9×	1e-04
heterochromatin formation	5	23.2×	2e-04
circadian regulation of gene expression	5	21.3×	3e-04
negative regulation of transforming growth factor beta receptor signaling pathway	5	15.8×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

27 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

452 predictions. Top by Δscore:

Variant	Effect	Δscore
20:49983137:TCCAG:T	donor_gain	1.0000
20:49983140:AG:A	donor_gain	1.0000
20:49983141:GG:G	donor_gain	1.0000
20:49983142:G:GG	donor_gain	1.0000
20:49983142:GTGC:G	donor_loss	1.0000
20:49983820:TCAG:T	acceptor_gain	1.0000
20:49983821:CAG:C	acceptor_gain	1.0000
20:49983822:A:AG	acceptor_gain	1.0000
20:49983822:AG:A	acceptor_loss	1.0000
20:49983822:AGA:A	acceptor_gain	1.0000
20:49983823:G:GT	acceptor_gain	1.0000
20:49983823:GA:G	acceptor_gain	1.0000
20:49983823:GAG:G	acceptor_gain	1.0000
20:49983823:GAGT:G	acceptor_gain	1.0000
20:49983823:GAGTT:G	acceptor_gain	1.0000
20:49983983:A:T	donor_gain	1.0000
20:49983104:G:GT	donor_gain	0.9900
20:49983129:GACTC:G	donor_gain	0.9900
20:49983138:CCAG:C	donor_gain	0.9900
20:49983139:CAG:C	donor_gain	0.9900
20:49983819:CTCAG:C	acceptor_gain	0.9900
20:49983820:TCAGA:T	acceptor_gain	0.9900
20:49983821:CAGA:C	acceptor_gain	0.9900
20:49983822:AGAGT:A	acceptor_gain	0.9900
20:49984019:A:G	donor_gain	0.9900
20:49984299:G:GT	donor_gain	0.9900
20:49984299:G:T	donor_gain	0.9900
20:49984349:CTGG:C	donor_loss	0.9900
20:49984350:TGGTA:T	donor_loss	0.9900
20:49984352:G:GA	donor_loss	0.9900

AlphaMissense

1699 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:49984306:T:C	F189L	1.000
20:49984308:C:A	F189L	1.000
20:49984308:C:G	F189L	1.000
20:49987910:T:C	F217L	1.000
20:49987912:C:A	F217L	1.000
20:49987912:C:G	F217L	1.000
20:49987994:T:C	F245L	1.000
20:49987996:C:A	F245L	1.000
20:49987996:C:G	F245L	1.000
20:49984207:T:C	C156R	0.999
20:49984247:T:C	L169P	0.999
20:49984257:C:A	H172Q	0.999
20:49984257:C:G	H172Q	0.999
20:49984269:C:A	H176Q	0.999
20:49984269:C:G	H176Q	0.999
20:49984307:T:C	F189S	0.999
20:49984347:C:A	H202Q	0.999
20:49984347:C:G	H202Q	0.999
20:49987883:T:C	F208L	0.999
20:49987885:C:A	F208L	0.999
20:49987885:C:G	F208L	0.999
20:49987889:T:C	C210R	0.999
20:49987910:T:A	F217I	0.999
20:49987911:T:C	F217S	0.999
20:49987929:T:C	L223P	0.999
20:49987937:C:A	H226N	0.999
20:49987937:C:G	H226D	0.999
20:49987939:C:A	H226Q	0.999
20:49987939:C:G	H226Q	0.999
20:49987951:C:A	H230Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000245738 (20:49981313 G>A,C), RS1000704106 (20:49982464 T>C), RS1000770376 (20:49988381 G>A), RS1001031031 (20:49981869 C>A,T), RS1001091670 (20:49982376 G>C), RS1001382413 (20:49985794 A>T), RS1001633935 (20:49985615 C>T), RS1001914521 (20:49985398 G>A), RS1002166344 (20:49985542 G>C), RS1002943130 (20:49988715 C>T), RS1003079381 (20:49988446 AC>A), RS1003726295 (20:49984386 T>C), RS1003884231 (20:49984715 C>A,G,T), RS1003983831 (20:49981476 T>C), RS1004855550 (20:49982447 C>A)

Disease associations

OMIM: gene MIM:604238 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000834_7	Psoriasis	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

249 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects reaction, increases activity, decreases reaction, increases abundance, increases expression (+4 more)	12
Estradiol	affects cotreatment, decreases expression, decreases reaction, increases expression, increases reaction	9
Cadmium Chloride	decreases reaction, increases expression, increases abundance, decreases expression, affects reaction	8
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases abundance, increases reaction, decreases expression	7
Cadmium	decreases reaction, increases abundance, increases expression, decreases expression, affects cotreatment (+2 more)	7
bisphenol A	affects binding, decreases expression, decreases reaction, increases expression, affects cotreatment	6
Arsenic Trioxide	decreases expression, affects cotreatment, increases reaction, affects reaction, decreases reaction	6
Fulvestrant	decreases reaction, increases expression	6
Acetylcysteine	decreases reaction, increases expression, increases abundance, decreases expression	6
Benzo(a)pyrene	decreases expression, increases expression, increases mutagenesis, affects methylation	6
Resveratrol	decreases reaction, increases expression, decreases expression	4
Cisplatin	affects cotreatment, decreases expression, increases reaction, increases expression, decreases response to substance	4
Niclosamide	decreases response to substance, increases expression, increases phosphorylation, decreases expression, decreases reaction	4
arsenite	affects binding, increases reaction, increases expression, affects reaction	3
SB 203580	decreases reaction, increases expression, increases abundance, decreases expression	3
SB 216763	decreases reaction, increases expression, affects localization	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases reaction, increases abundance, increases expression	3
Lapatinib	affects cotreatment, decreases reaction, increases abundance, increases expression, increases reaction (+1 more)	3
Arsenic	decreases reaction, increases abundance, increases expression, increases reaction, affects cotreatment (+2 more)	3
Dexamethasone	decreases reaction, increases expression, decreases expression	3
Glucose	affects cotreatment, decreases reaction, increases expression, increases reaction	3
Tobacco Smoke Pollution	increases expression	3
Tretinoin	decreases expression, increases expression, affects expression	3
Particulate Matter	decreases reaction, increases abundance, increases expression, affects reaction	3
aristolochic acid I	decreases expression, increases expression	2
thymoquinone	decreases expression, decreases reaction, increases reaction	2
salinomycin	decreases reaction, increases activity, increases expression	2
cobaltous chloride	affects localization, increases expression, decreases reaction	2
potassium chromate(VI)	affects cotreatment, increases expression, decreases expression	2
diallyl disulfide	affects reaction, decreases reaction, increases expression, decreases expression	2

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6J6	SEES3-1V human SNAI1, clone1	Embryonic stem cell	Male
CVCL_A6J7	SEES3-1V human SNAI1, clone2	Embryonic stem cell	Male
CVCL_A6J8	SEES3-1V human SNAI1, clone3	Embryonic stem cell	Male
CVCL_B2GR	Abcam HeLa SNAI1 KO	Cancer cell line	Female
CVCL_B8PT	Abcam HCT 116 SNAI1 KO	Cancer cell line	Male
CVCL_B9S9	Abcam A-549 SNAI1 KO	Cancer cell line	Male
CVCL_D8B2	Ubigene A-549 SNAI1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.