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Slc12a3 solute carrier family 12, member 3 [ Mus musculus (house mouse) ]

Gene ID: 20497, updated on 27-Nov-2024

Summary

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Official Symbol
Slc12a3provided by MGI
Official Full Name
solute carrier family 12, member 3provided by MGI
Primary source
MGI:MGI:108114
See related
Ensembl:ENSMUSG00000031766 AllianceGenome:MGI:108114
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
NCC; TSC; NCCT
Summary
Enables sodium:chloride symporter activity. Involved in several processes, including response to aldosterone; response to dietary excess; and sodium ion transmembrane transport. Located in apical plasma membrane and cytosol. Is active in plasma membrane. Is expressed in metanephros. Used to study Gitelman syndrome. Human ortholog(s) of this gene implicated in Gitelman syndrome and essential hypertension. Orthologous to human SLC12A3 (solute carrier family 12 member 3). [provided by Alliance of Genome Resources, Nov 2024]
Expression
Restricted expression toward kidney adult (RPKM 195.7) See more
Orthologs
human all
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Genomic context

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See Slc12a3 in Genome Data Viewer
Location:
8 C5; 8 46.46 cM
Exon count:
25
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 8 NC_000074.7 (95055737..95092850)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 8 NC_000074.6 (94329109..94366222)

Chromosome 8 - NC_000074.7Genomic Context describing neighboring genes Neighboring gene ribosomal protein L10, pseudogene 5 Neighboring gene nucleoporin 93 Neighboring gene microRNA 138-2 Neighboring gene STARR-positive B cell enhancer ABC_E8256 Neighboring gene STARR-positive B cell enhancer ABC_E3794 Neighboring gene STARR-positive B cell enhancer ABC_E2270 Neighboring gene predicted gene 15889 Neighboring gene homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. CD8(+) T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension. Liu Y, et al. Nat Commun, 2017 Jan 9. PMID 28067240, Free PMC Article
  2. Rapid Aldosterone-Mediated Signaling in the DCT Increases Activity of the Thiazide-Sensitive NaCl Cotransporter. Cheng L, et al. J Am Soc Nephrol, 2019 Aug. PMID 31253651, Free PMC Article
  3. A new model of the distal convoluted tubule. Ko B, et al. Am J Physiol Renal Physiol, 2012 Sep. PMID 22718890, Free PMC Article
  4. Low-dose L-NAME induces salt sensitivity associated with sustained increased blood volume and sodium-chloride cotransporter activity in rodents. Wang C, et al. Kidney Int, 2020 Nov. PMID 32592815
  5. The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension. Hoorn EJ, et al. Nat Med, 2011 Oct 2. PMID 21963515, Free PMC Article

See all (167) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Differential IL18 signaling via IL18 receptor and Na-Cl co-transporter discriminating thermogenesis and glucose metabolism regulation.
    Title: Differential IL18 signaling via IL18 receptor and Na-Cl co-transporter discriminating thermogenesis and glucose metabolism regulation.
  2. 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.
  3. High dietary potassium causes ubiquitin-dependent degradation of the kidney sodium-chloride cotransporter.
    Title: High dietary potassium causes ubiquitin-dependent degradation of the kidney sodium-chloride cotransporter.
  4. Renal Natriuretic Peptide Receptor-C Deficiency Attenuates NaCl Cotransporter Activity in Angiotensin II-Induced Hypertension.
    Title: Renal Natriuretic Peptide Receptor-C Deficiency Attenuates NaCl Cotransporter Activity in Angiotensin II-Induced Hypertension.
  5. Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted Tubule.
    Title: Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted Tubule.
  6. Aldosterone acutely activates NCC to modulate renal NaCl excretion.
    Title: Rapid Aldosterone-Mediated Signaling in the DCT Increases Activity of the Thiazide-Sensitive NaCl Cotransporter.
  7. This study reveal that lack of renal NCC causes an aldosterone-mediated upregulation of circulating FGF23.
    Title: Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC).
  8. Modulation of WNK4 activity by intracellular chloride [Cl(-)]i is not the sole mechanism for regulating NCC. Increased luminal NaCl delivery upregulates NCC via yet unknown mechanism(s) that may override inhibition of WNK4 by high [Cl(-)]i.
    Title: Differential roles of WNK4 in regulation of NCC in vivo.
  9. Aldosterone promotes increased interaction of NCC and ENaC.
    Title: Aldosterone Modulates the Association between NCC and ENaC.
  10. Kir4.1 plays an essential role in mediating the effect of dietary potassium intake on NCC activity and potassium homeostasis.
    Title: Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel.
Submit: New GeneRIF Correction See all GeneRIFs (55)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables enzyme binding ISO
Inferred from Sequence Orthology
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sodium ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables sodium ion transmembrane transporter activity ISO
Inferred from Sequence Orthology
more info
  
enables sodium:chloride symporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables sodium:chloride symporter activity ISO
Inferred from Sequence Orthology
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 chloride transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in chloride transport ISO
Inferred from Sequence Orthology
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 protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in renal sodium ion absorption IEA
Inferred from Electronic Annotation
more info
  
involved_in renal sodium ion absorption ISO
Inferred from Sequence Orthology
more info
  
involved_in response to aldosterone IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to dietary excess IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
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 IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in sodium ion transmembrane transport ISO
Inferred from Sequence Orthology
more info
  
involved_in sodium ion transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in sodium ion transport ISO
Inferred from Sequence Orthology
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 ISO
Inferred from Sequence Orthology
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular exosome IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome ISO
Inferred from Sequence Orthology
more info
  
is_active_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in plasma membrane ISO
Inferred from Sequence Orthology
more info
  
located_in plasma membrane ISO
Inferred from Sequence Orthology
more info
  
located_in vesicle ISO
Inferred from Sequence Orthology
more info
  

General protein information

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Preferred Names
solute carrier family 12 member 3
Names
Na-Cl symporter
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.

mRNA and Protein(s)

  1. NM_001205311.1 → NP_001192240.1  solute carrier family 12 member 3 isoform 1

    See identical proteins and their annotated locations for NP_001192240.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC128663, AK052691
    Consensus CDS
    CCDS57632.1
    UniProtKB/Swiss-Prot
    P59158
    UniProtKB/TrEMBL
    Q543E4, Q62439
    Related
    ENSMUSP00000034218.4, ENSMUST00000034218.5
    Conserved Domains (3) summary
    TIGR00930
    Location:57 → 1001
    2a30; K-Cl cotransporter
    pfam03522
    Location:653 → 1001
    SLC12; Solute carrier family 12
    pfam08403
    Location:43 → 113
    AA_permease_N; Amino acid permease N-terminal

  2. NM_019415.2 → NP_062288.2  solute carrier family 12 member 3 isoform 2

    See identical proteins and their annotated locations for NP_062288.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    AI647800, AI882166, AK052691
    UniProtKB/TrEMBL
    Q62439
    Conserved Domains (3) summary
    TIGR00930
    Location:57 → 1000
    2a30; K-Cl cotransporter
    pfam03522
    Location:652 → 1000
    SLC12; Solute carrier family 12
    pfam08403
    Location:43 → 112
    AA_permease_N; Amino acid permease N-terminal

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000074.7 Reference GRCm39 C57BL/6J

    Range
    95055737..95092850
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017312625.1 → XP_017168114.1  solute carrier family 12 member 3 isoform X1

    UniProtKB/TrEMBL
    Q62439
    Conserved Domains (1) summary
    TIGR00930
    Location:57 → 1008
    2a30; K-Cl cotransporter

  2. XM_017312626.1 → XP_017168115.1  solute carrier family 12 member 3 isoform X2

    UniProtKB/TrEMBL
    Q62439
    Conserved Domains (1) summary
    TIGR00930
    Location:57 → 1007
    2a30; K-Cl cotransporter

  3. XM_017312627.2 → XP_017168116.1  solute carrier family 12 member 3 isoform X3

    Conserved Domains (1) summary
    TIGR00930
    Location:57 → 561
    2a30; K-Cl cotransporter

RNA

  1. XR_001778414.1 RNA Sequence

  2. XR_004934784.1 RNA Sequence

Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P59158.1 GenPept UniProtKB/Swiss-Prot:P59158

Gene LinkOut

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