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SLC12A1 solute carrier family 12 member 1 [ Homo sapiens (human) ]

Gene ID: 6557, updated on 17-Mar-2024

Summary

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Official Symbol
SLC12A1provided by HGNC
Official Full Name
solute carrier family 12 member 1provided by HGNC
Primary source
HGNC:HGNC:10910
See related
Ensembl:ENSG00000074803 MIM:600839; AllianceGenome:HGNC:10910
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
BSC; BSC1; CCC2; BSC-1; NKCC2
Summary
This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]
Expression
Restricted expression toward kidney (RPKM 306.7) See more
Orthologs
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Genomic context

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Location:
15q21.1
Exon count:
29
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (48206302..48304078)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (46014393..46112359)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (48498499..48596275)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene solute carrier family 24 member 5 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:48442018-48442582 Neighboring gene myelin expression factor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6412 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6413 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr15:48470436-48471087 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:48483866-48484369 Neighboring gene CTXN2 antisense RNA 1 Neighboring gene cortexin 2 Neighboring gene uncharacterized LOC128966560 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:48543423-48544622 Neighboring gene MPRA-validated peak2328 silencer Neighboring gene uncharacterized LOC124903486 Neighboring gene DUT antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:48621665-48621855 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:48623134-48623660 Neighboring gene Sharpr-MPRA regulatory region 3998 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6416 Neighboring gene deoxyuridine triphosphatase

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Diacidic Motifs in the Carboxyl Terminus Are Required for ER Exit and Translocation to the Plasma Membrane of NKCC2. Bakhos-Douaihy D, et al. Int J Mol Sci, 2022 Oct 23. PMID 36361553, Free PMC Article
  2. Novel SLC12A1 mutations cause Bartter syndrome in two patients with different prognoses. Yi S, et al. Clin Chim Acta, 2022 Jun 1. PMID 35358470
  3. [Functional characterization of SLC12A1 gene variants in 3 patients with Bartter syndrome type Ⅰ]. Sha YG, et al. Zhonghua Er Ke Za Zhi, 2022 Feb 2. PMID 35090230
  4. Golgi Alpha1,2-Mannosidase IA Promotes Efficient Endoplasmic Reticulum-Associated Degradation of NKCC2. Demaretz S, et al. Cells, 2021 Dec 29. PMID 35011665, Free PMC Article
  5. New insights into the role of endoplasmic reticulum-associated degradation in Bartter Syndrome Type 1. Shaukat I, et al. Hum Mutat, 2021 Aug. PMID 33973684

See all (70) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. AUP1 Regulates the Endoplasmic Reticulum-Associated Degradation and Polyubiquitination of NKCC2.
    Title: AUP1 Regulates the Endoplasmic Reticulum-Associated Degradation and Polyubiquitination of NKCC2.
  2. 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.
  3. Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer.
    Title: Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer.
  4. Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma.
    Title: Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma.
  5. Diacidic Motifs in the Carboxyl Terminus Are Required for ER Exit and Translocation to the Plasma Membrane of NKCC2.
    Title: Diacidic Motifs in the Carboxyl Terminus Are Required for ER Exit and Translocation to the Plasma Membrane of NKCC2.
  6. Novel SLC12A1 mutations cause Bartter syndrome in two patients with different prognoses.
    Title: Novel SLC12A1 mutations cause Bartter syndrome in two patients with different prognoses.
  7. New insights into the role of endoplasmic reticulum-associated degradation in Bartter Syndrome Type 1.
    Title: New insights into the role of endoplasmic reticulum-associated degradation in Bartter Syndrome Type 1.
  8. Golgi Alpha1,2-Mannosidase IA Promotes Efficient Endoplasmic Reticulum-Associated Degradation of NKCC2.
    Title: Golgi Alpha1,2-Mannosidase IA Promotes Efficient Endoplasmic Reticulum-Associated Degradation of NKCC2.
  9. [Functional characterization of SLC12A1 gene variants in 3 patients with Bartter syndrome type ].
    Title: [Functional characterization of SLC12A1 gene variants in 3 patients with Bartter syndrome type Ⅰ].
  10. Differential Effects of STCH and Stress-Inducible Hsp70 on the Stability and Maturation of NKCC2.
    Title: Differential Effects of STCH and Stress-Inducible Hsp70 on the Stability and Maturation of NKCC2.
Submit: New GeneRIF Correction See all GeneRIFs (48)

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
Bartter disease type 1
MedGen: C1866495 OMIM: 601678 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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

Clone Names

  • MGC48843

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables sodium:potassium:chloride symporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables sodium:potassium:chloride symporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables sodium:potassium:chloride symporter activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in cell volume homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cell volume homeostasis IDA
Inferred from Direct Assay
more info
 PubMed 
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 transmembrane transport ISS
Inferred from Sequence or Structural Similarity
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 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
  
Component Evidence Code Pubs
is_active_in apical plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_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 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 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
solute carrier family 12 member 1
Names
Na-K-2Cl cotransporter
Na-K-2Cl cotransporter 2
bumetanide-sensitive cotransporter type 1
bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2
kidney-specific Na-K-Cl symporter
solute carrier family 12 (sodium/potassium/chloride transporter), member 1
solute carrier family 12 (sodium/potassium/chloride transporters), member 1

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

  1. NG_021301.1 RefSeqGene

    Range
    5002..102778
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000338.3 → NP_000329.2  solute carrier family 12 member 1 isoform A

    See identical proteins and their annotated locations for NP_000329.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform A. Isoforms A and F are the same length but differ in the region of amino acids 214-238.
    Source sequence(s)
    AA917702, AC023355, BC040138, DA632985, U58130
    Consensus CDS
    CCDS10129.2
    UniProtKB/Swiss-Prot
    A8JYA2, E9PDW4, Q13621
    UniProtKB/TrEMBL
    A0A2R8Y6V7
    Related
    ENSP00000370381.3, ENST00000380993.8
    Conserved Domains (3) summary
    TIGR00930
    Location:104 → 1099
    2a30; K-Cl cotransporter
    pfam03522
    Location:694 → 1099
    SLC12; Solute carrier family 12
    pfam08403
    Location:90 → 156
    AA_permease_N; Amino acid permease N-terminal

  2. NM_001184832.2 → NP_001171761.1  solute carrier family 12 member 1 isoform F

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame exon in the 5' coding region, compared to variant 1, and encodes isoform F. Isoforms A and F are the same length but differ in the region of amino acids 214-238.
    Source sequence(s)
    AA917702, AC023355, AK298312, DA632985, U58130
    Consensus CDS
    CCDS53940.1
    UniProtKB/TrEMBL
    A0A2R8Y6V7
    Related
    ENSP00000379822.3, ENST00000396577.7
    Conserved Domains (3) summary
    TIGR00930
    Location:104 → 1099
    2a30; K-Cl cotransporter
    pfam03522
    Location:694 → 1099
    SLC12; Solute carrier family 12
    pfam08403
    Location:90 → 156
    AA_permease_N; Amino acid permease N-terminal

  3. NM_001384136.1 → NP_001371065.1  solute carrier family 12 member 1 isoform B

    Status: REVIEWED

    Source sequence(s)
    AC023355, AC066612
    Consensus CDS
    CCDS91995.1
    UniProtKB/TrEMBL
    A0A2R8Y6V7, A0A8I5KSK6
    Related
    ENSP00000508901.1, ENST00000686073.1
    Conserved Domains (1) summary
    TIGR00930
    Location:104 → 1099
    2a30; K-Cl cotransporter

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_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    48206302..48304078
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    46014393..46112359
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13621.2 GenPept UniProtKB/Swiss-Prot:Q13621

Gene LinkOut

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