SLC12A4

solute carrier family 12 member 4, the group of Solute carrier family 12

Basic information

Region (hg38): 16:67943474-67969601

Links

ENSG00000124067 ∙ NCBI:6560 ∙ OMIM:604119 ∙ HGNC:10913 ∙ Uniprot:Q9UP95 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC12A4 gene.

• not provided (2 variants)
• Fish-eye disease (1 variants)
• Norum disease;Fish-eye disease (1 variants)
• Cardiovascular phenotype (1 variants)
• LCAT deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC12A4 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	1		4
missense			87	5		92
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding	3	2	15	18	2	40
Total	3	2	105	24	2

Highest pathogenic variant AF is 0.0000197

Variants in SLC12A4

This is a list of pathogenic ClinVar variants found in the SLC12A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-67943479-T-C			Benign (Aug 30, 2018)
16-67943793-A-C			Benign (May 04, 2019)
16-67943929-G-C			Likely benign (Feb 19, 2024)
16-67943933-C-T			Likely benign (Nov 07, 2023)
16-67943943-C-T		Norum disease	Uncertain significance (-)
16-67943946-A-ACCGAGGATGACGGG		Norum disease;Fish-eye disease	Likely pathogenic (Feb 19, 2024)
16-67943949-G-A		Cardiovascular phenotype	Likely benign (Nov 02, 2024)
16-67943957-C-T		Cardiovascular phenotype • Fish-eye disease;Norum disease	Uncertain significance (May 28, 2024)
16-67943958-G-A			Likely benign (Jan 29, 2024)
16-67943962-C-T			Uncertain significance (Dec 22, 2024)
16-67943966-T-A		Cardiovascular phenotype	Uncertain significance (Feb 12, 2022)
16-67943982-A-G		Cardiovascular phenotype	Likely benign (Oct 24, 2024)
16-67943984-C-A		Norum disease;Fish-eye disease	Uncertain significance (Apr 04, 2024)
16-67943984-C-G		Cardiovascular phenotype	Uncertain significance (Jun 28, 2023)
16-67943986-T-A		Norum disease;Fish-eye disease	Uncertain significance (Jan 18, 2024)
16-67943986-T-C		Cardiovascular phenotype	Uncertain significance (Nov 02, 2021)
16-67943987-T-A		Norum disease;Fish-eye disease	Likely pathogenic (May 08, 2024)
16-67943988-G-C		Cardiovascular phenotype	Likely benign (Dec 23, 2021)
16-67943991-C-T		Cardiovascular phenotype	Likely benign (May 17, 2024)
16-67943992-G-A		Cardiovascular phenotype • Norum disease;Fish-eye disease	Conflicting classifications of pathogenicity (Nov 19, 2024)
16-67943995-G-A		Norum disease;Fish-eye disease	Uncertain significance (Mar 07, 2024)
16-67944000-C-T		Cardiovascular phenotype	Likely benign (Jan 01, 2025)
16-67944000-C-CG		LCAT deficiency • Cardiovascular phenotype	Pathogenic (Apr 06, 2023)
16-67944001-G-A		Fish-eye disease • Norum disease;Fish-eye disease	Pathogenic (May 29, 2024)
16-67944009-G-A		Cardiovascular phenotype	Likely benign (Feb 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC12A4	protein_coding	protein_coding	ENST00000422611	23	26128

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.05e-11	1.00	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	594	694	0.855	0.0000447	7000
Missense in Polyphen		272	331.63	0.82019		3369
Synonymous	-0.989	318	296	1.07	0.0000202	2280
Loss of Function	3.48	27	54.8	0.493	0.00000282	566

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000824	0.000812
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000943	0.0000924
European (Non-Finnish)	0.000294	0.000290
Middle Eastern	0.000218	0.000217
South Asian	0.000261	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity. {ECO:0000250}.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle 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: 0.272

Intolerance Scores

• loftool: 0.0282
• rvis_EVS: -1.92
• rvis_percentile_EVS: 1.93

Haploinsufficiency Scores

• pHI: 0.429
• hipred: Y
• hipred_score: 0.597
• ghis: 0.669

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.572

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc12a4
• Phenotype: immune system phenotype; renal/urinary system phenotype; respiratory system phenotype; liver/biliary system phenotype; hematopoietic system 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); 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)

Gene ontology

• Biological process: ion transport;cell volume homeostasis;chemical synaptic transmission;chloride ion homeostasis;potassium ion homeostasis;chloride transmembrane transport;potassium ion import across plasma membrane
• Cellular component: lysosomal membrane;plasma membrane;integral component of plasma membrane;membrane
• Molecular function: potassium:chloride symporter activity;protein kinase binding