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

    Gene ID: 6557, updated on 27-Nov-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
    mouse all
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    Genomic context

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    See SLC12A1 in Genome Data Viewer
    Location:
    15q21.1
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (48206302..48304078)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (46014393..46112359)
    RS_2024_09 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. Eleven novel SLC12A1 variants and an exonic mutation cause exon skipping in Bartter syndrome type I. Han Y, et al. Endocrine, 2019 Jun. PMID 30790175
    2. Na+-K+-2Cl- cotransporter type 2 trafficking and activity: the role of interacting proteins. Carmosino M, et al. Biol Cell, 2012 Apr. PMID 22211456
    3. Immunolocalization of a Na-K-2Cl cotransporter in human tracheobronchial smooth muscle. Iwamoto LM, et al. J Appl Physiol (1985), 2003 Apr. PMID 12471046
    4. Atypical phenotype of type I Bartter syndrome accompanied by focal segmental glomerulosclerosis. Yamazaki H, et al. Pediatr Nephrol, 2009 Feb. PMID 18830715
    5. Bartter and related syndromes: the puzzle is almost solved. Rodríguez-Soriano J. Pediatr Nephrol, 1998 May. PMID 9655365

    See all (75) 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
    		Compare labs

    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)

    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 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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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