U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from MedGen

    • Showing Current items.

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

    Gene ID: 6559, updated on 19-Jun-2024

    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See SLC12A3 in Genome Data Viewer
    Location:
    16q13
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (56865207..56915850)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (62661526..62712168)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (56899119..56949762)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 1622 Neighboring gene nucleoporin 93 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:56885802-56886009 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10853 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10854 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:56901109-56901693 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:56901694-56902278 Neighboring gene microRNA 138-2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10855 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10856 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:56908501-56909437 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:56910353-56910852 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:56926577-56927308 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10857 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:56937172-56937352 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:56937981-56938489 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr16:56946332-56947531 Neighboring gene ribosomal protein S24 pseudogene 17 Neighboring gene microRNA 6863 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:56965546-56966100 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:56966101-56966655 Neighboring gene Sharpr-MPRA regulatory region 13851 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10862 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7516 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7517 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10863 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10864 Neighboring gene uncharacterized LOC124903811 Neighboring gene homocysteine inducible ER protein with ubiquitin like domain 1

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    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
    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

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ96318

    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 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

    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)

    NEW Try the new Transcript table

    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

    1. NG_009386.2 RefSeqGene

      Range
      5001..55644
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000339.3NP_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:591029
      2a30; K-Cl cotransporter
    2. NM_001126107.2NP_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:591028
      2a30; K-Cl cotransporter
    3. NM_001126108.2NP_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:591020
      2a30; K-Cl cotransporter
    4. NM_001410896.1NP_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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      56865207..56915850
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      62661526..62712168
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)