SLC12A2

solute carrier family 12 member 2, the group of Solute carrier family 12|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 5:128083766-128189677

Links

ENSG00000064651 ∙ NCBI:6558 ∙ OMIM:600840 ∙ HGNC:10911 ∙ Uniprot:P55011 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• hearing loss, autosomal dominant 78 (Strong), mode of inheritance: AD
• Delpire-McNeill syndrome (Strong), mode of inheritance: AD
• Kilquist syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 78; Delpire-McNeill syndrome; Kilquist syndrome	AD/AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary	The conditions can include early-onset hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Kilquist syndrome, antiinfectious prophylaxis and early and aggressive treatment of infections, as well as aggressive pulmonary care, may be beneficial	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary	30740830; 32658972; 32754646

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC12A2 gene.

• not provided (4 variants)
• SLC12A2-related disorder (1 variants)
• Sensorineural hearing loss disorder (1 variants)
• Inborn genetic diseases (1 variants)
• Kilquist syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC12A2 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				61	7	68
missense	1		191	12	3	207
nonsense	3	3	2			8
start loss						0
frameshift	1		3			4
inframe indel			21	4	2	27
splice donor/acceptor (+/-2bp)	1	2	2			5
splice region			5	5	1	11
non coding			3	42	25	70
Total	6	5	222	119	37

Highest pathogenic variant AF is 0.00000659

Variants in SLC12A2

This is a list of pathogenic ClinVar variants found in the SLC12A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-128083958-G-C			Uncertain significance (Aug 30, 2023)
5-128083972-G-C		SLC12A2-related disorder	Likely benign (Dec 26, 2023)
5-128083995-G-T		Kilquist syndrome;Hearing loss, autosomal dominant 78;Delpire-McNeill syndrome • Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
5-128083999-G-C			Likely benign (Aug 01, 2024)
5-128084006-G-T		Inborn genetic diseases	Uncertain significance (Jun 12, 2023)
5-128084018-C-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
5-128084031-CGCTGGCCGCAGCCAGGGTGGAACT-C			Uncertain significance (Dec 17, 2022)
5-128084053-A-G			Benign (Jul 16, 2022)
5-128084056-G-A		Delpire-McNeill syndrome;Kilquist syndrome;Hearing loss, autosomal dominant 78	Benign/Likely benign (Mar 01, 2024)
5-128084067-C-G			Uncertain significance (Jun 01, 2024)
5-128084073-C-T		Delpire-McNeill syndrome	Uncertain significance (May 20, 2023)
5-128084074-C-T			Likely benign (Aug 18, 2023)
5-128084081-C-G			Uncertain significance (Jul 01, 2022)
5-128084091-C-T			Uncertain significance (Nov 06, 2023)
5-128084099-G-C			Uncertain significance (Aug 23, 2022)
5-128084101-G-C			Likely benign (Sep 18, 2023)
5-128084101-G-T			Benign (Jun 01, 2024)
5-128084108-G-A		Delpire-McNeill syndrome	Uncertain significance (-)
5-128084110-C-G			Benign (Aug 01, 2024)
5-128084113-C-T			Likely benign (Mar 10, 2022)
5-128084131-G-T			Uncertain significance (Jun 10, 2023)
5-128084133-G-T		Inborn genetic diseases	Uncertain significance (May 25, 2022)
5-128084138-G-A			Uncertain significance (May 15, 2023)
5-128084144-G-A			Uncertain significance (Sep 01, 2022)
5-128084150-G-A		Inborn genetic diseases	Uncertain significance (Jun 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC12A2	protein_coding	protein_coding	ENST00000262461	27	105923

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.962	0.0385	125714	0	20	125734	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.40	430	594	0.723	0.0000293	7818
Missense in Polyphen		135	259.89	0.51945		3207
Synonymous	-0.473	222	213	1.04	0.0000107	2407
Loss of Function	5.77	11	58.7	0.188	0.00000309	736

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000127	0.000126
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000350	0.0000327
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
• Pathway: Vibrio cholerae infection - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Cation-coupled Chloride cotransporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.315

Intolerance Scores

• loftool: 0.0758
• rvis_EVS: -1.31
• rvis_percentile_EVS: 4.88

Haploinsufficiency Scores

• pHI: 0.229
• hipred: Y
• hipred_score: 0.639
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.757

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc12a2
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); reproductive 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); 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); growth/size/body region 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: slc12a2
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: area

Gene ontology

• Biological process: ion transport;cell volume homeostasis;hyperosmotic response;gamma-aminobutyric acid signaling pathway;aging;T cell chemotaxis;ammonium transport;transepithelial chloride transport;sodium ion transmembrane transport;positive regulation of cell volume;chloride ion homeostasis;potassium ion homeostasis;sodium ion homeostasis;transepithelial ammonium transport;ammonium transmembrane transport;chloride transmembrane transport;potassium ion import across plasma membrane;cellular response to chemokine
• Cellular component: plasma membrane;integral component of plasma membrane;membrane;apical plasma membrane;extracellular exosome;extracellular vesicle
• Molecular function: protein binding;sodium:potassium:chloride symporter activity;ammonium transmembrane transporter activity;sodium ion transmembrane transporter activity;sodium:chloride symporter activity;potassium:chloride symporter activity;protein kinase binding