SNAI2

Summary

SNAI2 (snail family transcriptional repressor 2, HGNC:11094) is a protein-coding gene on chromosome 8q11.21, encoding Zinc finger protein SNAI2 (O43623). Transcriptional repressor that modulates both activator-dependent and basal transcription.

This gene encodes a member of the Snail family of C2H2-type zinc finger transcription factors. The encoded protein acts as a transcriptional repressor that binds to E-box motifs and is also likely to repress E-cadherin transcription in breast carcinoma. This protein is involved in epithelial-mesenchymal transitions and has antiapoptotic activity. Mutations in this gene may be associated with sporatic cases of neural tube defects.

Source: NCBI Gene 6591 — RefSeq curated summary.

At a glance

• Gene–disease (curated): piebaldism (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 111 total
• Phenotypes (HPO): 25
• Transcription factor: yes — 54 downstream targets (CollecTRI)
• MANE Select transcript: NM_003068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11094
Approved symbol	SNAI2
Name	snail family transcriptional repressor 2
Location	8q11.21
Locus type	gene with protein product
Status	Approved
Aliases	SLUGH1, SNAIL2, SLUGH
Ensembl gene	ENSG00000019549
Ensembl biotype	protein_coding
OMIM	602150
Entrez	6591

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000020945, ENST00000396822, ENST00000649776

RefSeq mRNA: 1 — MANE Select: NM_003068 NM_003068

CCDS: CCDS6146

Canonical transcript exons

ENST00000020945 — 3 exons

Exon	Start	End
ENSE00001526387	48917598	48918988
ENSE00001674368	48919896	48920441
ENSE00002250662	48921187	48921429

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.1854 / max 792.3435, expressed in 1295 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93002	40.5902	1269
93001	13.9236	1071
93004	0.3286	179
93003	0.2419	128
93005	0.1012	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.37	gold quality
cartilage tissue	UBERON:0002418	98.24	gold quality
stromal cell of endometrium	CL:0002255	96.58	gold quality
upper leg skin	UBERON:0004262	95.70	gold quality
upper arm skin	UBERON:0004263	95.59	gold quality
skin of hip	UBERON:0001554	95.36	gold quality
periodontal ligament	UBERON:0008266	95.31	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.28	gold quality
cauda epididymis	UBERON:0004360	94.37	gold quality
seminal vesicle	UBERON:0000998	93.92	gold quality
calcaneal tendon	UBERON:0003701	93.83	gold quality
hair follicle	UBERON:0002073	93.61	gold quality
penis	UBERON:0000989	93.51	gold quality
left uterine tube	UBERON:0001303	93.27	gold quality
gingiva	UBERON:0001828	93.02	gold quality
parietal pleura	UBERON:0002400	92.95	gold quality
mammary duct	UBERON:0001765	92.80	gold quality
mammalian vulva	UBERON:0000997	92.78	gold quality
gingival epithelium	UBERON:0001949	92.60	gold quality
endocervix	UBERON:0000458	92.53	gold quality
vagina	UBERON:0000996	92.45	gold quality
ectocervix	UBERON:0012249	92.15	gold quality
nipple	UBERON:0002030	92.05	gold quality
epithelium of mammary gland	UBERON:0003244	92.02	gold quality
endometrium	UBERON:0001295	91.94	gold quality
decidua	UBERON:0002450	91.88	gold quality
zone of skin	UBERON:0000014	91.82	gold quality
uterine cervix	UBERON:0000002	91.66	gold quality
superficial temporal artery	UBERON:0001614	91.54	gold quality
myometrium	UBERON:0001296	91.38	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	1290.77
E-MTAB-8221	yes	955.48
E-MTAB-10662	yes	863.41
E-MTAB-10485	yes	480.16
E-MTAB-9388	yes	435.98
E-HCAD-10	yes	58.06
E-ANND-3	yes	17.03
E-CURD-112	yes	13.85
E-HCAD-13	yes	12.92
E-MTAB-5061	yes	11.22
E-MTAB-7052	no	3170.94
E-ENAD-20	no	720.49

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

54 targets.

Target	Regulation
ACAN	Unknown
ADAM2
BRCA1	Repression
BRCA2	Unknown
CCND1	Activation
CD44	Activation
CDH1	Repression
CDH17
CDH2	Unknown
CDH3	Repression
CDH5	Unknown
CLDN1	Activation
COL2A1	Unknown
CTNNB1
CXADR	Repression
CXCL12	Activation
CXCR4	Activation
CYP24A1	Repression
ESR1	Repression
FOXA1	Activation
HPGD	Repression
ITGA3	Repression
ITGB1	Repression
ITGB4	Repression
JAG1	Activation
JUP	Unknown
KLF4	Repression
KRT19	Repression
KRT8	Repression
L1CAM	Unknown

JASPAR motifs

Motif	Name	Family
MA0745.1	SNAI2	More than 3 adjacent zinc fingers
MA0745.2	SNAI2	More than 3 adjacent zinc fingers
MA0745.3	SNAI2	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:25100569, PMID:23332764

Upstream regulators (CollecTRI, top): AHR, AR, ATF3, BCL11B, BHLHE41, CREB1, CTNNB1, CUX1, E2F1, EGR1, ELF1, ERG, ESR1, ESRRA, EZH2, FOSL1, FOXA1, FOXA2, FOXC1, FOXM1, HDAC1, HDAC2, JAG1, KLF4, LEF1, MITF, MTA1, MYB, NCOR1, NOTCH1, OVOL2, PER2, POU2F1, RELA, RUNX2, SATB2, SIM2, SMAD1, SMAD2, SNAI1

miRNA regulators (miRDB)

133 targeting SNAI2, 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-6867-5P	100.00	82.21	3464
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-7110-3P	100.00	73.18	2486
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394

Literature-anchored findings (GeneRIF, showing 40)

• The SLUG zinc-finger protein represses E-cadherin in breast cancer. (PMID:11912130)
• Absence of SLUG causes the auditory-pigmentary symptoms in at least some individuals with Wardenburg syndrome type 2. (PMID:12444107)
• Results suggest that aberrant expression of Snail or Slug may promote tumorigenesis through increased resistance to programmed cell death. (PMID:15314165)
• induction of Slug by autocrine production of SCF and c-Kit activation plays a key role in chemoresistance of malignant mesothelioma (PMID:15337769)
• Tumors with positive Slug expression invaded deeper, had more lymph node metastasis, and had more lymphatic invasion than the tumors with negative Slug expression. (PMID:15709186)
• SLUG is a negative regulator for BRCA2 gene expression (PMID:15734731)
• SLUG levels in the cell regulated the function of cytokeratins 8 and 19 gene promoters. (PMID:15737616)
• High levels of Snail predict decreased relapse-free survival in women with breast cancer. (PMID:16169465)
• SLUG is upregulated by dihydrotestosterone and epidermal growth factor, providing a molecular mechanism by which epithelial cell-specific genes are silenced during prostate cancer development and progression. (PMID:16541421)
• Slug regulates integrin alpha3, beta1, and beta4 expression and cell proliferation in human epidermal keratinocytes (PMID:16707493)
• Slug overexpression may contribute to specific cardiac phenotypes and cancer development. (PMID:16717446)
• These findings support a role of Slug in mediating Raf 1-induced transcriptional repression of occludin and subsequent epithelial to mesenchymal transition. (PMID:16924233)
• Results suggest that the aryl hydrocarbon receptor participates in Slug induction, which, in turn, regulates cellular physiology including cell adhesion and migration. (PMID:16952353)
• we provide evidence through yeast two-hybrid and in vitro co-immunoprecipitation analyses that hSLUG does not directly interact with hCtBP1. (PMID:17194444)
• 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)
• Ligand-induced Notch activation, through the induction of Slug, promotes tumor growth and metastasis characterized by epithelial-to-mesenchymal transition. (PMID:17984306)
• Myocardin-related transcription factors are critical mediators of transforming growth factor beta (TGF-beta) 1-induced epithelial-mesenchymal transition.[ (PMID:18056415)
• Knockdown of SIM2s in MCF-7 breast cancer cells contributed to an epithelial-mesenchymal transition associated with increased slug levels. (PMID:18160708)
• SLUG binds to the E2-box sequences of the VDR gene promoter and recruits CtBP1 and HDAC1, which results in the inhibition of VDR gene expression by chromatin remodeling. (PMID:18485278)
• The effect of Etrogen receptor alpha on slug repression is dependent on the overall level of ERalpha, confirming that slug is an estrogen receptor alpha responsive gene. (PMID:18588516)
• Slug down-regulation facilitates apoptosis induced by proapoptotic drugs in neuroblastoma cells and decreases their invasion capability in vitro and in vivo (PMID:18628477)
• Collectively, our data suggest that combined expression of Slug and Snail is required for EMT in cardiac cushion morphogenesis. (PMID:18663143)
• Slug is an essential component of the pathway leading to EGFR-mediated epithelial outgrowth (PMID:18685621)
• These results implicate a novel EGFR/Erk5/Slug pathway in the control of cytoskeleton organization and cell motility in keratinocytes treated with epidermal growth factor. (PMID:18716062)
• Snail and Slug promote formation of beta-catenin-T-cell factor (TCF)-4 transcription complexes that bind to the promoter of the TGF-beta3 gene to increase its transcription. (PMID:18799618)
• SLUG-induced epithelial-mesenchymal transition may alter the expression profile of receptor tyrosine kinases, including discoid domain receptors (PMID:18853422)
• Factors released by breast cancer cells are able to upregulate Slug expression in vascular endothelial cells. (PMID:19046938)
• We found upregulation of mRNA for transcription factors Snail, Slug, Twist, and SIP1 in spindle cell carcinoma when compared to squamous cell carcinoma. (PMID:19381684)
• changes in the Akt/beta-catenin pathway play key roles in the regulation of E-cadherin through the transactivation of the Slug gene in uterine carcinosarcomas. (PMID:19389926)
• Results indicate that wtp53 and p53 mutants may differentially control cancer invasion and metastasis through the p53-MDM2-Slug pathway. (PMID:19448627)
• Overexpression of Snail2 cooperates with Snail1 in the repression of vitamin D receptor in colon cancer. (PMID:19502595)
• TGF-beta1 increases Slug via ERK1/2 signaling, and thereby contributes to oral squamous cell carcinoma progression. (PMID:19681038)
• aids in Wnt/beta-catenin signal transduction in invasive ductal carcinoma of breast (PMID:19751508)
• Slug functions as a novel regulator of osteoblast activity and may be considered a new factor required for osteoblast maturation. (PMID:19756381)
• Data show that elevated Snail expression by Pdcd4 knockdown leads to downregulation of E-cadherin resulting in activating beta-catenin/Tcf-dependent transcription. (PMID:19784072)
• Coexpression of Snail and Twist correlated with the worst prognosis of hepatocellular carcinoma. (PMID:19821482)
• Studies suggest a model of hypoxia induced metastasis through expression of HIF-1alpha, and SLUG regulation of MT4-MMP transcription. (PMID:20019845)
• Data show there was a strong inverse correlation between slug and ERalpha and E-cadherin immunoreactivity in breast cancer cases. (PMID:20101232)
• Results suggest that SLUG expression is correlated with osteogenic commitment, and is positively regulated by Lef-1 signal in normal human osteoblasts. (PMID:20128911)
• transcription factors Snail1 and Snail2 repress vitamin D receptor during colon cancer progression (PMID:20138990)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Snai2	ENSMUSG00000022676
drosophila_melanogaster	wor	FBGN0001983

Paralogs (36): ZBTB32 (ENSG00000011590), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), 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 SNAI2 — O43623 (reviewed: O43623)

Alternative names: Neural crest transcription factor Slug, Protein snail homolog 2

All UniProt accessions (2): A0A1X7SC17, O43623

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor that modulates both activator-dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transcriptional repression of the TJ protein, occludin (OCLN) and subsequent oncogenic transformation of epithelial cells. Represses BRCA2 expression by binding to its E2-box-containing silencer and recruiting CTBP1 and HDAC1 in breast cells. In epidermal keratinocytes, binds to the E-box in ITGA3 promoter and represses its transcription. Involved in the regulation of ITGB1 and ITGB4 expression and cell adhesion and proliferation in epidermal keratinocytes. Binds to E-box2 domain of BSG and activates its expression during TGFB1-induced epithelial-mesenchymal transition (EMT) in hepatocytes. Represses E-Cadherin/CDH1 transcription via E-box elements. Involved in osteoblast maturation. Binds to RUNX2 and SOC9 promoters and may act as a positive and negative transcription regulator, respectively, in osteoblasts. Binds to CXCL12 promoter via E-box regions in mesenchymal stem cells and osteoblasts. Plays an essential role in TWIST1-induced EMT and its ability to promote invasion and metastasis.

Subunit / interactions. Interacts (via SNAG domain) with LIMD1 (via LIM domains), WTIP (via LIM domains) and AJUBA (via LIM domains). Interacts (via zinc fingers) with KPNA2, KPNB1, and TNPO1. May interact (via zinc fingers) with IPO7.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in most adult human tissues, including spleen, thymus, prostate, testis, ovary, small intestine, colon, heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Not detected in peripheral blood leukocyte. Expressed in the dermis and in all layers of the epidermis, with high levels of expression in the basal layers (at protein level). Expressed in osteoblasts (at protein level). Expressed in mesenchymal stem cells (at protein level). Expressed in breast tumor cells (at protein level).

Post-translational modifications. Phosphorylated by GSK3B. Once phosphorylated, it becomes a target for ubiquitination. Ubiquitinated by the SCF(FBXO11) complex; ubiquitination requires previous GSK3B-mediated SNAI2 phosphorylation.

Disease relevance. Waardenburg syndrome 2D (WS2D) [MIM:608890] WS2 is a genetically heterogeneous, autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, and absence of dystopia canthorum. The frequency of deafness is higher in WS2 than in WS1. The disease is caused by variants affecting the gene represented in this entry. Piebald trait (PBT) [MIM:172800] Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Repression activity depends on the C-terminal DNA-binding zinc fingers and on the N-terminal repression domain.

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

RefSeq proteins (1): NP_003059* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050527

Pfam: PF00096

UniProt features (23 total): mutagenesis site 11, zinc finger region 5, sequence variant 3, region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43623-F1	64.87	0.09

Functional residue map

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

Mutagenesis-validated functional residues (11):

Position	Phenotype
87	increases protein stability. does not affect repressor activity on e-cadherin/cdh1 promoter.
92	increases protein stability, nuclear accumulation and repressor activity on e-cadherin/cdh1 promoter; when associated wi
96	increases protein stability, nuclear accumulation and repressor activity on e-cadherin/cdh1 promoter; when associated wi
100	increases protein stability and half-life, nuclear accumulation and repressor activity on e-cadherin/cdh1 promoter; when
104	increases protein stability and half-life, nuclear accumulation and repressor activity on e-cadherin/cdh1 promoter; when
166	abolishes binding to kpna2, kpnb1 and ipo7 and impairs binding to tmpo1; when associated with e-175.
175	abolishes binding to kpna2, kpnb1 and ipo7 and impairs binding to tmpo1; when associated with e-166.
192	abolishes binding to kpna2 and impairs binding to kpnb1, ipo7 and tmpo1; when associated with e-196.
196	abolishes binding to kpna2 and impairs binding to kpnb1, ipo7 and tmpo1; when associated with e-192.
225	abolishes binding to kpna2, kpnb1 and ipo7 and impairs binding to tmpo1; when associated with e-229.
229	abolishes binding to kpna2, kpnb1 and ipo7 and impairs binding to tmpo1; when associated with e-225.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-6807070	PTEN Regulation
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9730414	MITF-M-regulated melanocyte development

MSigDB gene sets: 479 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CELL_MIGRATION_INVOLVED_IN_HEART_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (45): negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), epithelial to mesenchymal transition (GO:0001837), aortic valve morphogenesis (GO:0003180), epithelial to mesenchymal transition involved in endocardial cushion formation (GO:0003198), cell migration involved in endocardial cushion formation (GO:0003273), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355), negative regulation of cell adhesion involved in substrate-bound cell migration (GO:0006933), Notch signaling pathway (GO:0007219), sensory perception of sound (GO:0007605), epithelial cell migration (GO:0010631), negative regulation of keratinocyte proliferation (GO:0010839), negative regulation of vitamin D biosynthetic process (GO:0010957), neural crest cell development (GO:0014032), positive regulation of cell migration (GO:0030335), negative regulation of chondrocyte differentiation (GO:0032331), regulation of chemokine production (GO:0032642), myeloid cell apoptotic process (GO:0033028), negative regulation of myeloid cell apoptotic process (GO:0033033), negative regulation of cell adhesion mediated by integrin (GO:0033629), desmosome disassembly (GO:0035921), pigmentation (GO:0043473), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), endothelial cell migration (GO:0043542), positive regulation of fat cell differentiation (GO:0045600), regulation of osteoblast differentiation (GO:0045667), white fat cell differentiation (GO:0050872), roof of mouth development (GO:0060021), epithelium development (GO:0060429), cartilage morphogenesis (GO:0060536), regulation of branching involved in salivary gland morphogenesis (GO:0060693), negative regulation of vitamin D receptor signaling pathway (GO:0070563), cellular response to epidermal growth factor stimulus (GO:0071364), hematopoietic stem cell proliferation (GO:0071425), cellular response to ionizing radiation (GO:0071479), negative regulation of canonical Wnt signaling pathway (GO:0090090), negative regulation of hematopoietic stem cell proliferation (GO:1902034), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), regulation of bicellular tight junction assembly (GO:2000810)

GO Molecular Function (12): 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 factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), chromatin binding (GO:0003682), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
PTEN Regulation	1
Regulation of CDH1 Gene Transcription	1
MITF-M-regulated melanocyte development	1
Intracellular signaling by second messengers	1
PIP3 activates AKT signaling	1
Signal Transduction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
endocardial cushion formation	2
binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
ossification	1
cell differentiation	1
mesenchymal cell differentiation	1
aortic valve development	1
heart valve morphogenesis	1
cardiac epithelial to mesenchymal transition	1
cell migration involved in heart development	1
cellular component organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
substrate-dependent cell migration	1
negative regulation of cell adhesion	1
cell surface receptor signaling pathway	1
sensory perception of mechanical stimulus	1
ameboidal-type cell migration	1
epithelium migration	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
negative regulation of epithelial cell proliferation	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
neural crest cell differentiation	1
stem cell development	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
chondrocyte differentiation	1
regulation of chondrocyte differentiation	1
negative regulation of cell differentiation	1
negative regulation of cartilage development	1

Protein interactions and networks

STRING

3550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNAI2	TWIST1	Q15672	936
SNAI2	KDM1A	O60341	933
SNAI2	CDH1	P12830	930
SNAI2	SOX9	P48436	903
SNAI2	CDH2	P19022	887
SNAI2	VIM	P08670	881
SNAI2	SOX10	P56693	842
SNAI2	SIN3A	Q96ST3	840
SNAI2	SMAD4	Q13485	839
SNAI2	CTNNB1	P35222	801
SNAI2	SMAD2	Q15796	800
SNAI2	FOXD3	Q9UJU5	794
SNAI2	TWIST2	Q8WVJ9	790
SNAI2	PAX3	P23760	781
SNAI2	TP53	P04637	780

IntAct

17 interactions, top by confidence:

A	B	Type	Score
TRIM23	SNAI2	psi-mi:“MI:0915”(physical association)	0.560
SNAI2	SAT1	psi-mi:“MI:0915”(physical association)	0.560
SNAI2	TRIM23	psi-mi:“MI:0915”(physical association)	0.560
SAT1	SNAI2	psi-mi:“MI:0915”(physical association)	0.560
SNAI2	CSNK2A1	psi-mi:“MI:0915”(physical association)	0.560
SNAI2	CABP2	psi-mi:“MI:0915”(physical association)	0.560
SNAI2	ZNF76	psi-mi:“MI:0915”(physical association)	0.560
SNAI2		psi-mi:“MI:0914”(association)	0.350
CABP2	SNAI2	psi-mi:“MI:0915”(physical association)	0.000
ZNF76	SNAI2	psi-mi:“MI:0915”(physical association)	0.000
CSNK2A1	SNAI2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (90): SNAI2 (Two-hybrid), SNAI2 (Two-hybrid), SNAI2 (Affinity Capture-RNA), MDM2 (Affinity Capture-Western), SNAI2 (Affinity Capture-Western), SNAI2 (Affinity Capture-Western), USP17L2 (Affinity Capture-Western), SNAI2 (Affinity Capture-Western), FBXO31 (Affinity Capture-Western), DAXX (Affinity Capture-Western), SNAI2 (Affinity Capture-Western), USP10 (Affinity Capture-Western), SNAI2 (Affinity Capture-Western), UBE2I (Two-hybrid), SNAI2 (Affinity Capture-Western)

ESM2 similar proteins: A0JPB4, A1L1J6, A4IFJ6, D3ZUU2, E9Q8T2, G5E8B9, O08954, O15060, O42409, O43623, O57415, O70237, O75626, O95625, P19382, P25932, P36197, P37275, P97469, Q20082, Q2EI20, Q3MHQ4, Q3UH06, Q4VBD9, Q5DU09, Q5R9W9, Q5SVQ8, Q5T0B9, Q5ZLR2, Q60542, Q60636, Q62947, Q64318, Q6DCW1, Q6GNP2, Q6INV8, Q6NRM0, Q7TS63, Q7ZVR6, Q80X44

Diamond homologs: O08954, O43623, P08044, P19382, P25932, P97469, Q3KNW1, Q3MHQ4, Q91924, O95863, A2ANX9, A7Y7X5, O62836, P08048, P10925, P17010, P17012, P20662, P28166, P31508, P31509, P80944, Q01611, Q01797, Q01798, Q01799, Q01800, Q02025, Q02026, Q02027, Q02085, Q29419, Q52V16, Q5RAU9, Q642B2, Q6B4Z5, Q6ZNH5, Q8BI66, Q8BTH6, Q8TF50

SIGNOR signaling

39 interactions.

A	Effect	B	Mechanism
ESRRA	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
CREB1	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
EZH2	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
PER2	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
POU2F1	“up-regulates quantity by expression”	SNAI2	“transcriptional regulation”
SUZ12	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
HDAC2	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
HDAC1	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
NCOR1	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
ESR1	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
MTA1	“up-regulates quantity by expression”	SNAI2	“transcriptional regulation”
RUNX2	“up-regulates quantity by expression”	SNAI2	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	JAG1	“transcriptional regulation”
TNF	“up-regulates quantity by expression”	SNAI2	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	CD44	“transcriptional regulation”
SNAI2	“down-regulates quantity by repression”	ESR1	“transcriptional regulation”
SNAI2	“down-regulates quantity by repression”	CDH1	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	CXCL12	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	MMP9	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	CXCR4	“transcriptional regulation”
SNAI2	“down-regulates quantity by repression”	HPGD	“transcriptional regulation”
SNAI2	“down-regulates quantity by repression”	UBE2D3	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	CCND1	“transcriptional regulation”
SNAI2	“down-regulates quantity by repression”	VDR	“transcriptional regulation”
TWIST1	“up-regulates quantity by expression”	SNAI2	“transcriptional regulation”
ZMYND8	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
FBXO45	“down-regulates quantity by destabilization”	SNAI2	binding
“Skp1-Pam E3”	“down-regulates quantity by destabilization”	SNAI2	polyubiquitination
CyclinE/CDK2	“down-regulates quantity by destabilization”	SNAI2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	32
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

177 predictions. Top by Δscore:

Variant	Effect	Δscore
8:48920437:AATCA:A	acceptor_gain	1.0000
8:48920438:ATCA:A	acceptor_gain	1.0000
8:48920439:TCA:T	acceptor_gain	1.0000
8:48920440:CA:C	acceptor_gain	1.0000
8:48920440:CAC:C	acceptor_gain	1.0000
8:48920442:C:CC	acceptor_gain	1.0000
8:48920442:C:CG	acceptor_loss	1.0000
8:48920443:T:A	acceptor_loss	1.0000
8:48921181:TTTTA:T	donor_loss	1.0000
8:48921182:TTTAC:T	donor_loss	1.0000
8:48921183:TTA:T	donor_loss	1.0000
8:48921184:TA:T	donor_loss	1.0000
8:48921185:A:C	donor_loss	1.0000
8:48921186:C:CT	donor_loss	1.0000
8:48919894:AC:A	donor_gain	0.9900
8:48919895:CC:C	donor_gain	0.9900
8:48919889:CTCTT:C	donor_loss	0.9800
8:48919890:TCTTA:T	donor_loss	0.9800
8:48919891:CTTA:C	donor_loss	0.9800
8:48919892:TTA:T	donor_loss	0.9800
8:48919893:T:TC	donor_loss	0.9800
8:48921185:A:AC	donor_gain	0.9800
8:48921186:C:CC	donor_gain	0.9800
8:48918987:CC:C	acceptor_gain	0.9700
8:48918988:CC:C	acceptor_gain	0.9700
8:48918995:G:GC	acceptor_gain	0.9700
8:48919000:G:GC	acceptor_gain	0.9700
8:48918987:CCCT:C	acceptor_loss	0.9600
8:48918989:C:CG	acceptor_loss	0.9600
8:48918990:T:C	acceptor_loss	0.9600

AlphaMissense

1760 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:48918847:A:G	L256P	1.000
8:48918864:G:C	F250L	1.000
8:48918864:G:T	F250L	1.000
8:48918866:A:G	F250L	1.000
8:48918909:A:C	H235Q	1.000
8:48918909:A:T	H235Q	1.000
8:48918919:A:G	L232P	1.000
8:48918921:A:C	H231Q	1.000
8:48918921:A:T	H231Q	1.000
8:48918923:G:C	H231D	1.000
8:48918923:G:T	H231N	1.000
8:48918931:A:G	L228P	1.000
8:48918948:A:C	F222L	1.000
8:48918948:A:T	F222L	1.000
8:48918949:A:G	F222S	1.000
8:48918950:A:G	F222L	1.000
8:48918950:A:T	F222I	1.000
8:48918962:A:G	C218R	1.000
8:48918971:A:G	C215R	1.000
8:48918975:A:C	F213L	1.000
8:48918975:A:T	F213L	1.000
8:48918976:A:G	F213S	1.000
8:48918977:A:G	F213L	1.000
8:48919900:G:C	H207Q	1.000
8:48919900:G:T	H207Q	1.000
8:48919902:G:C	H207D	1.000
8:48919906:T:A	R205S	1.000
8:48919906:T:G	R205S	1.000
8:48919907:C:G	R205T	1.000
8:48919912:G:C	H203Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000348337 (8:48917448 TTAA>T), RS1001112717 (8:48921628 T>G), RS1001427871 (8:48922887 T>C), RS1001479347 (8:48923000 A>T), RS1002433657 (8:48921552 T>C), RS1002435978 (8:48918001 C>T), RS1002737250 (8:48919151 AT>A), RS1004359269 (8:48919567 G>A), RS1004841313 (8:48919132 C>G), RS1005725682 (8:48917718 G>C,T), RS1006254547 (8:48917488 A>G), RS1007136469 (8:48923289 C>A), RS1007233586 (8:48921770 A>G), RS1007596832 (8:48923292 C>G), RS1008141290 (8:48921820 T>C,G)

Disease associations

OMIM: gene MIM:602150 | disease phenotypes: MIM:172800, MIM:608890

GenCC curated gene-disease

Disease	Classification	Inheritance
piebaldism	Definitive	Autosomal dominant
Waardenburg syndrome type 2D	Strong	Autosomal recessive
Waardenburg syndrome	Strong	Autosomal recessive
Waardenburg syndrome type 2	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Waardenburg syndrome	Limited	AR

Mondo (4): piebaldism (MONDO:0008244), Waardenburg syndrome type 2D (MONDO:0012144), Waardenburg syndrome type 2 (MONDO:0019517), Waardenburg syndrome (MONDO:0018094)

Orphanet (2): Piebaldism (Orphanet:2884), Waardenburg syndrome (Orphanet:3440)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000077	Abnormality of the kidney
HP:0000252	Microcephaly
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000664	Synophrys
HP:0001053	Hypopigmented skin patches
HP:0001100	Heterochromia iridis
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0002211	White forelock
HP:0002216	Premature graying of hair
HP:0002226	White eyebrow
HP:0002227	White eyelashes
HP:0002251	Aganglionic megacolon
HP:0002683	Abnormal calvaria morphology
HP:0004414	Abnormality of the pulmonary artery
HP:0005599	Hypopigmentation of hair
HP:0007544	Piebald skin depigmentation
HP:0008069	Neoplasm of the skin
HP:0012733	Macule

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012229_63	Hip index	9.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D016116	Piebaldism	C16.320.290.040.600; C16.320.565.100.102.600; C16.320.850.080.600; C17.800.621.440.102.600; C17.800.827.080.600; C18.452.648.100.102.600
D014849	Waardenburg Syndrome	C16.131.077.938
C563839	Waardenburg Syndrome, Type 2D (supp.)
C536463	Waardenburg syndrome type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases expression, affects cotreatment, decreases expression, increases reaction (+1 more)	9
sodium arsenite	increases expression, increases reaction, affects cotreatment, decreases expression, decreases reaction (+1 more)	8
bisphenol A	increases expression, decreases expression, decreases reaction	6
Resveratrol	affects cotreatment, decreases expression, decreases reaction, increases expression	6
Arsenic Trioxide	affects cotreatment, increases expression, decreases expression, increases reaction, affects reaction	6
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	5
Tetrachlorodibenzodioxin	affects reaction, increases expression, affects binding, increases reaction	4
Tretinoin	affects expression, increases expression, decreases expression, increases reaction	4
trichostatin A	affects cotreatment, increases expression	3
Fulvestrant	decreases reaction, increases expression	3
Arsenic	increases reaction, affects cotreatment, decreases expression, decreases reaction, increases abundance (+1 more)	3
Cadmium	decreases expression, increases abundance, affects cotreatment, decreases response to substance, increases expression	3
Cisplatin	increases expression, affects cotreatment, decreases response to substance, decreases reaction	3
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	affects reaction, decreases expression, increases abundance, increases expression, decreases reaction	3
methylmercuric chloride	increases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
cordycepin	decreases expression, decreases localization, increases reaction	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases abundance, increases expression, increases reaction	2
chloropicrin	affects expression, decreases expression	2
U 0126	decreases reaction, increases expression, increases abundance, increases reaction	2
AG 1879	decreases expression, decreases reaction, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases reaction	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Chlorpyrifos	affects localization, increases expression	2

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6J9	SEES3-1V human SNAI2, clone1	Embryonic stem cell	Male
CVCL_A6K0	SEES3-1V human SNAI2, clone2	Embryonic stem cell	Male
CVCL_A6K1	SEES3-1V human SNAI2, clone3	Embryonic stem cell	Male
CVCL_B8PU	Abcam HCT 116 SNAI2 KO	Cancer cell line	Male
CVCL_B9SA	Abcam A-549 SNAI2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01377077	PHASE4	UNKNOWN	Punchgrafting Techniques for Vitiligo
NCT01640678	PHASE4	UNKNOWN	Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients
NCT02458417	PHASE4	COMPLETED	Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients
NCT02156427	PHASE3	COMPLETED	Evaluation of Non-cultured Epidermal Cellular Grafting vs Hyaluronic Acid for Repigmenting Vitiligo and Piebaldism
NCT04919993	Not specified	COMPLETED	CBT for Insomnia in Primary Brain Tumor Patients
NCT02418936	Not specified	UNKNOWN	Development and Clinical Application of Two New Genetic Deafness Gene Diagnostic Kit