SLC12A3 solute carrier family 12 member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC12A3provided by HGNC
Official Full Name: solute carrier family 12 member 3provided by HGNC
Primary source: HGNC:HGNC:10912
See related: Ensembl:ENSG00000070915 MIM:600968; AllianceGenome:HGNC:10912
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NCC; TSC; NCCT
Summary: This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Restricted expression toward kidney (RPKM 65.2) See more
Orthologs: mouse all
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Genomic context

Location:: 16q13

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (56865207..56915850)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (62661526..62712168)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (56899119..56949762)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

From Fish Physiology to Human Disease: The Discovery of the NCC, NKCC2, and the Cation-Coupled Chloride Cotransporters.
Title: From Fish Physiology to Human Disease: The Discovery of the NCC, NKCC2, and the Cation-Coupled Chloride Cotransporters.
Spectrum of variants in a large Chinese Gitelman syndrome cohort.
Title: Spectrum of variants in a large Chinese Gitelman syndrome cohort.
Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome.
Title: Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome.
Novel heterozygous mutations of SLC12A3 gene in a Chinese pedigree with Gitelman syndrome: A care-compliant case report.
Title: Novel heterozygous mutations of SLC12A3 gene in a Chinese pedigree with Gitelman syndrome: A care-compliant case report.
Minigene splicing assays reveal new insights into exonic variants of the SLC12A3 gene in Gitelman syndrome.
Title: Minigene splicing assays reveal new insights into exonic variants of the SLC12A3 gene in Gitelman syndrome.
Upregulation of SLC12A3 and SLC12A9 Mediated by the HCP5/miR-140-5p Axis Confers Aggressiveness and Unfavorable Prognosis in Uveal Melanoma.
Title: Upregulation of SLC12A3 and SLC12A9 Mediated by the HCP5/miR-140-5p Axis Confers Aggressiveness and Unfavorable Prognosis in Uveal Melanoma.
Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter.
Title: Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter.
R158Q and G212S, novel pathogenic compound heterozygous variants in SLC12A3 of Gitelman syndrome.
Title: R158Q and G212S, novel pathogenic compound heterozygous variants in SLC12A3 of Gitelman syndrome.
Multiple molecular mechanisms are involved in the activation of the kidney sodium-chloride cotransporter by hypokalemia.
Title: Multiple molecular mechanisms are involved in the activation of the kidney sodium-chloride cotransporter by hypokalemia.
Detecting pathogenic deep intronic variants in Gitelman syndrome.
Title: Detecting pathogenic deep intronic variants in Gitelman syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (131)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Familial hypokalemia-hypomagnesemia MedGen: C0268450 OMIM: 263800 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: Genomewide analysis among 18 245 initially healthy women from the Women's Genome Health Study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70938 (e-PCR)
- UniSTS:19345

STS-X91220 (e-PCR)
- UniSTS:10160

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium:chloride symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium:chloride symporter activity	TAS Traceable Author Statement more info
enables sodium:potassium:chloride symporter activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in cell volume homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
involved_in potassium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in renal sodium ion absorption	IDA Inferred from Direct Assay more info	PubMed
involved_in response to aldosterone	IEA Inferred from Electronic Annotation more info
involved_in response to dietary excess	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
involved_in sodium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in sodium ion transport	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: solute carrier family 12 member 3

Names: Na-Cl cotransporter; Na-Cl symporter; NaCl electroneutral thiazide-sensitive cotransporter; sodium-chloride co-transporter; solute carrier family 12 (sodium/chloride transporter), member 3; thiazide-sensitive Na-Cl cotransporter; thiazide-sensitive sodium-chloride cotransporter

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009386.2 RefSeqGene

Range

5001..55644

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000339.3 → NP_000330.3 solute carrier family 12 member 3 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC012181

Consensus CDS

CCDS10770.1

Related

ENSP00000402152.2, ENST00000438926.6

Conserved Domains (1) summary

TIGR00930
Location:59 → 1029

2a30; K-Cl cotransporter
NM_001126107.2 → NP_001119579.2 solute carrier family 12 member 3 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in a protein (isoform 2) that is 1 aa shorter than isoform 1.

Source sequence(s)

AC012181

Consensus CDS

CCDS45491.1

Related

ENSP00000457552.1, ENST00000566786.5

Conserved Domains (1) summary

TIGR00930
Location:59 → 1028

2a30; K-Cl cotransporter
NM_001126108.2 → NP_001119580.2 solute carrier family 12 member 3 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a protein (isoform 3) that is 9 aa shorter than isoform 1.

Source sequence(s)

AC012181

Consensus CDS

CCDS58464.1

UniProtKB/Swiss-Prot

A8MSJ2, C9JNN9, P55017

Related

ENSP00000456149.2, ENST00000563236.6

Conserved Domains (1) summary

TIGR00930
Location:59 → 1020

2a30; K-Cl cotransporter
NM_001410896.1 → NP_001397825.1 solute carrier family 12 member 3 isoform 4

Status: REVIEWED

Source sequence(s)

AC012181

Consensus CDS

CCDS92165.1

UniProtKB/TrEMBL

J3QSS1

Related

ENSP00000262502.5, ENST00000262502.5