SNAI2

snail family transcriptional repressor 2, the group of Zinc fingers C2H2-type|SNAG transcriptional repressors

Basic information

Region (hg38): 8:48917598-48921740

Previous symbols: [ "SLUG" ]

Links

ENSG00000019549 ∙ NCBI:6591 ∙ OMIM:602150 ∙ HGNC:11094 ∙ Uniprot:O43623 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Waardenburg syndrome type 2D (Moderate), mode of inheritance: AR
• Waardenburg syndrome type 2 (Supportive), mode of inheritance: AD
• piebaldism (Supportive), mode of inheritance: AD
• piebaldism (Strong), mode of inheritance: AD
• Waardenburg syndrome type 2D (Strong), mode of inheritance: AR
• piebaldism (Definitive), mode of inheritance: AD
• Waardenburg syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Waardenburg syndrome, type 2D	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Dermatologic; Ophthalmologic	1717985; 9450866; 12444107; 12955764

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SNAI2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SNAI2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	23		26
missense			31	2	1	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			20	5	3	28
Total	0	0	54	30	4

Variants in SNAI2

This is a list of pathogenic ClinVar variants found in the SNAI2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-48917696-C-A		Piebaldism	Uncertain significance (Jan 12, 2018)
8-48917781-C-T		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48917843-C-T		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48917888-A-G		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48918034-G-T		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48918295-A-G		Piebaldism	Uncertain significance (Jan 12, 2018)
8-48918378-C-T		Piebaldism	Uncertain significance (Mar 30, 2018)
8-48918379-G-A		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48918387-G-T		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48918467-A-C		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48918473-A-C		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48918658-G-T		Piebaldism	Likely benign (Jan 13, 2018)
8-48918678-C-A		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48918761-G-A		Piebaldism	Uncertain significance (Jan 13, 2018)
8-48918781-G-A		Piebaldism	Uncertain significance (Jan 12, 2018)
8-48918851-G-C		not specified	Uncertain significance (Dec 08, 2023)
8-48918885-G-A		Piebaldism	Uncertain significance (Jan 12, 2018)
8-48918889-T-C			Uncertain significance (Jul 18, 2022)
8-48918954-T-C			Likely benign (Apr 25, 2022)
8-48918991-G-C			Uncertain significance (May 12, 2022)
8-48918993-G-T			Likely benign (Aug 29, 2024)
8-48919006-G-GA			Benign (Oct 25, 2024)
8-48919690-A-G			Benign (Dec 17, 2018)
8-48919891-C-A			Uncertain significance (Jul 24, 2024)
8-48919915-T-A			Likely benign (Sep 06, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SNAI2	protein_coding	protein_coding	ENST00000396822	3	4051

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.795	0.204	125538	0	1	125539	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	101	139	0.725	0.00000686	1759
Missense in Polyphen		17	54.055	0.3145		665
Synonymous	-0.399	61	57.2	1.07	0.00000312	521
Loss of Function	2.57	1	9.60	0.104	4.57e-7	129

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). 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. {ECO:0000250, ECO:0000269|PubMed:10866665, ECO:0000269|PubMed:11912130, ECO:0000269|PubMed:15734731, ECO:0000269|PubMed:16707493, ECO:0000269|PubMed:19756381, ECO:0000269|PubMed:21182836}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:12444107}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Piebald trait (PBT) [MIM:172800]: Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. {ECO:0000269|PubMed:12955764}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Adherens junction - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Neural Crest Differentiation;Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;Kit receptor signaling pathway;TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition;miR-509-3p alteration of YAP1-ECM axis;EMT transition in Colorectal Cancer;Signal Transduction;downregulated of mta-3 in er-negative breast tumors;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Direct p53 effectors;Intracellular signaling by second messengers;Regulation of nuclear beta catenin signaling and target gene transcription;Signaling events mediated by Stem cell factor receptor (c-Kit) (Consensus)

Recessive Scores

• pRec: 0.326

Intolerance Scores

• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.351
• hipred: Y
• hipred_score: 0.699
• ghis: 0.633

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Snai2
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; pigmentation phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;osteoblast differentiation;epithelial to mesenchymal transition;aortic valve morphogenesis;epithelial to mesenchymal transition involved in endocardial cushion formation;cell migration involved in endocardial cushion formation;regulation of transcription, DNA-templated;negative regulation of cell adhesion involved in substrate-bound cell migration;Notch signaling pathway;sensory perception of sound;negative regulation of keratinocyte proliferation;negative regulation of vitamin D biosynthetic process;neural crest cell development;positive regulation of cell migration;negative regulation of chondrocyte differentiation;regulation of chemokine production;negative regulation of cell adhesion mediated by integrin;positive regulation of histone acetylation;desmosome disassembly;pigmentation;negative regulation of DNA damage response, signal transduction by p53 class mediator;positive regulation of fat cell differentiation;regulation of osteoblast differentiation;white fat cell differentiation;roof of mouth development;epithelium development;cartilage morphogenesis;regulation of branching involved in salivary gland morphogenesis;negative regulation of vitamin D receptor signaling pathway;cellular response to epidermal growth factor stimulus;cellular response to ionizing radiation;negative regulation of canonical Wnt signaling pathway;negative regulation of cell-cell adhesion by negative regulation of transcription from RNA polymerase II promoter;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage;negative regulation of stem cell proliferation;regulation of bicellular tight junction assembly;negative regulation of anoikis;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytoplasm
• 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;DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding;sequence-specific DNA binding;metal ion binding;E-box binding