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SLC12A1 Gene

protein-coding   GIFtS: 64
GCID: GC15P048498

Solute Carrier Family 12 (Sodium/Potassium/Chloride Transporter),...

  See SLC12A1-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Solute Carrier Family 12 (Sodium/Potassium/Chloride Transporter),
Member 11 2
     Na-K-2Cl Cotransporter2
NKCC22 3 5     NKCC2A Variant A2
Bumetanide-Sensitive Sodium-(Potassium)-Chloride Cotransporter 22 3     Solute Carrier Family 12 (Sodium/Potassium/Chloride Transporters), Member
12
Kidney-Specific Na-K-Cl Symporter2 3     Solute Carrier Family 12 Member 12
BSC12     

External Ids:    HGNC: 109101   Entrez Gene: 65572   Ensembl: ENSG000000748037   OMIM: 6008395   UniProtKB: Q136213   

Export aliases for SLC12A1 gene to outside databases

Previous GC identifers: GC15P044057 GC15P041545 GC15P046078 GC15P046214 GC15P046215 GC15P046287 GC15P025334


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for SLC12A1 Gene:
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)

GeneCards Summary for SLC12A1 Gene:
SLC12A1 (solute carrier family 12 (sodium/potassium/chloride transporter), member 1) is a protein-coding gene. Diseases associated with SLC12A1 include bartter syndrome antenatal type 1, and bartter syndrome, type 1. GO annotations related to this gene include sodium:potassium:chloride symporter activity. An important paralog of this gene is SLC12A7.

UniProtKB/Swiss-Prot: S12A1_HUMAN, Q13621
Function: Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in
the regulation of ionic balance and cell volume

summary for SLC12A1 Gene:
NKCC cotransporters are membrane-bound channels that play a prominent role in a variety of epithelial
absorptive and secretory processes and a direct role in cell volume regulation. There are two NKCC isoforms;
NKCC1 and NKCC2. NKCC1 is found on almost all cells types and, importantly, is located on the basolateral
membrane of secretory epithelia. In contrast NKCC2 is found exclusively in the kidney, specifically on the
apical membrane of absorptive epithelia. The NKCC is distinguished from all other transporters by the fact
that it transports Na+, K+ and Cl- stoichiometrically by means of a tightly coupled mechanism that can be
blocked by loop diuretics. The NKCC is electrically silent (i.e. not driven by a membrane voltage, nor does
it establish one) and requires all three ions to be simultaneously present on the same side of the plasma
membrane. This is achieved by an allosteric effect where binding of one ion increases the apparent affinity
of the binding site for the other ions. NH4+ may substitute for K+ (especially at NKCC2), which has an
important role in NH4+ recycling and excretion of excess acid in the kidney. The NKCC involves a secondary
active transport process, despite its requirement for cellular ATPase. It is activated by phosphorylation,
which is mediated by PKC and PKA. CK2 binding sites are also present on the NKCC, but the significance is
unknown. Protein phosphatases act to reduce NKCC activity by dephosphorylating the transporter. Furthermore,
the intracellular concentration of ions, including Cl-, Na+, K+, Mg2+, Ca2+ and H+, has an effect on NKCC
activity. There is also evidence that depolymerization of the actin cytoskeleton is associated with NKCC
activation.




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000015.9  NT_010194.18  NC_018926.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the SLC12A1 gene promoter:
         TBP   POU2F1   POU2F1b   POU2F1a   ATF-2   FOXD3   POU2F1c   RSRFC4   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidSLC12A1 promoter sequence
   Search Chromatin IP Primers for SLC12A1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SLC12A1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 15q15-q21.1   Ensembl cytogenetic band:  15q21.1   HGNC cytogenetic band: 15q15-q21

SLC12A1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SLC12A1 gene location

GeneLoc information about chromosome 15         GeneLoc Exon Structure

GeneLoc location for GC15P048498:  view genomic region     (about GC identifiers)

Start:
48,483,861 bp from pter      End:
48,596,275 bp from pter
Size:
112,415 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: S12A1_HUMAN, Q13621 (See protein sequence)
Recommended Name: Solute carrier family 12 member 1  
Size: 1099 amino acids; 121450 Da
Secondary accessions: A8JYA2
Alternative splicing: 3 isoforms:  Q13621-1   Q13621-2   Q13621-3   

Explore the universe of human proteins at neXtProt for SLC12A1: NX_Q13621

Explore proteomics data for SLC12A1 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn446, Asn456
  • Modification sites at PhosphoSitePlus

  • See SLC12A1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_000329.2  NP_001171761.1  

    ENSEMBL proteins: 
     ENSP00000453602   ENSP00000453230   ENSP00000379822   ENSP00000331550   ENSP00000453409  
     ENSP00000454178   ENSP00000454054   ENSP00000370381  
    Reactome Protein details: Q13621

    SLC12A1 Human Recombinant Protein Products:

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    Browse Sino Biological Cell Lysates
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    Browse Proteins at Cloud-Clone Corp.

     
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    Search eBioscience for ELISAs for SLC12A1 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    SLC: Solute carriers

    IUPHAR Guide to PHARMACOLOGY protein family classification: Kidney-specific Na-K-Cl symporter
    SLC12 family of cation-coupled chloride transporters

    5 InterPro protein domains:
     IPR002443 Na/K/Cl_cotranspt
     IPR002445 Na/K/Cl_cotranspt2
     IPR004842 Na/K/Cl_cotransptS
     IPR013612 AA_permease_N
     IPR004841 AA-permease/SLC12A_dom

    Graphical View of Domain Structure for InterPro Entry Q13621

    ProtoNet protein and cluster: Q13621

    3 Blocks protein domains:
    IPB002443 Na-K-Cl co-transporter family signature
    IPB002445 Na-K-Cl co-transporter 2 signature
    IPB013612 Amino acid permease N-terminal


    UniProtKB/Swiss-Prot: S12A1_HUMAN, Q13621
    Similarity: Belongs to the SLC12A transporter family


    Find genes that share domains with SLC12A1           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: S12A1_HUMAN, Q13621
    Function: Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in
    the regulation of ionic balance and cell volume
    Enzyme regulation: Activated by WNK3

         Genatlas biochemistry entry for SLC12A1:
    solute carrier family 12 (sodium/potassium/chloride transfer 1,primary mediator of sodium and chloride
    reabsorption in the apical membrane thick ascending limb of the loop of Henle

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005215transporter activity ----
    GO:0005515protein binding ----
    GO:0008511sodium:potassium:chloride symporter activity TAS8640224
    GO:0015377cation:chloride symporter activity ----
         
    Find genes that share ontologies with SLC12A1           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for SLC12A1:
     Decreased viability with pacli 

         11 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Slc12a1):
     behavior/neurological  cardiovascular system  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  integument  mortality/aging  renal/urinary system  reproductive system 
     skeleton 

    Find genes that share phenotypes with SLC12A1           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for SLC12A1: Slc12a1tm1Haca Slc12a1tm1Tkh Slc12a1tm2Haca

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SLC12A1
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    hsa-miR-185* hsa-miR-130a* hsa-miR-561 hsa-miR-452* hsa-miR-23c hsa-miR-944 hsa-miR-876-3p hsa-miR-383
    SwitchGear 3'UTR luciferase reporter plasmidSLC12A1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat SLC12A1

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    S12A1_HUMAN, Q13621: Membrane; Multi-pass membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane4
    cytosol2
    nucleus2
    extracellular1
    peroxisome1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane TAS--
    GO:0016020membrane TAS7929272
    GO:0016021integral component of membrane IEA--
    GO:0016324apical plasma membrane ----
    GO:0070062extracellular vesicular exosome IDA15326289

    Find genes that share ontologies with SLC12A1           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for SLC12A1 About    
    See pathways by source

    SuperPathContained pathways About
    1Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds
    SLC-mediated transmembrane transport0.47
    Transport of inorganic cations/anions and amino acids/oligopeptides0.38
    Transmembrane transport of small molecules0.47
    Cation-coupled Chloride cotransporters0.00
    2Neuropathic Pain-Signaling in Dorsal Horn Neurons
    Aldosterone Signaling in Epithelial Cells0.47
    3Diuretics Pathway, Pharmacodynamics
    Diuretics Pathway, Pharmacodynamics


    Find genes that share SuperPaths with SLC12A1           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for SLC12A1
        Aldosterone Signaling in Epithelial Cells

    1 Reactome Pathway for SLC12A1
        Cation-coupled Chloride cotransporters

    1 PharmGKB Pathway for SLC12A1
        Diuretics Pathway, Pharmacodynamics

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for SLC12A1
    Interactions:

        GeneGlobe Interaction Network for SLC12A1

    STRING Interaction Network Preview (showing 3 interactants - click image to see more details)

    3 Interacting proteins for SLC12A1 (Q136213 ENSP000003703814) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    OXSR1O957473, ENSP000003117134I2D: score=1 STRING: ENSP00000311713
    STK39Q9UEW83, ENSP000003482784I2D: score=1 STRING: ENSP00000348278
    --ENSP000001954194STRING: ENSP00000195419
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001822kidney development ----
    GO:0006810transport TAS8640224
    GO:0006811ion transport TAS--
    GO:0006813potassium ion transport IEA--
    GO:0006814sodium ion transport IEA--

    Find genes that share ontologies with SLC12A1           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Compounds for SLC12A1 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    FurosemideNa+/2Cl-/K+ (NKCC) cotransporter inhibitor. Also antagonizes GABAA[54-31-9]
    BumetanideNa+/2Cl-/K+ (NKCC) cotransporter inhibitor[28395-03-1]

    3 HMDB Compounds for SLC12A1    About this table
    CompoundSynonyms CAS #PubMed Ids
    ChlorineCl2 (see all 13)16887-00-6--
    FurosemideAcetic acid potassium salt (see all 176)54-31-9--
    SodiumSodium (see all 2)7440-23-5--

    Selected DrugBank Compounds for SLC12A1 (see all 12)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Potassium ChlorideChlorid draselny [Czech] (see all 9)7447-40-7targetbinder16093448 17139284 16713495 11752352 17016423 16807401
    transportersubstrate16093448 17139284 16713495 11752352 17016423 16807401 16093448 17139284 16713495 11752352 17016423 16807401
    BumetanideBumetanida [INN-Spanish] (see all 2)28395-03-1targetinhibitor11752352 10561751 9587066 19141616 9690036
    Chlormerodrin-- 62-37-3targetinducer5455277 17139284 17016423 8391582
    FurosemideDihydroflumethiazide (see all 12)54-31-9targetinhibitor17460608 1092541 10653443 11752352
    QuinethazoneChinetazone [dcit] (see all 5)73-49-4targetinhibitor19636250 19474192 20528637 12538756
    Trichlormethiazide-- 133-67-5targetinhibitor17414671 11752352 20187262 14610216
    ChlorthalidoneChlorothalidone (see all 5)77-36-1targetinhibitor17139284 11752352 17016423
    HydroflumethiazideDihydroflumethazide (see all 6)135-09-1targetinhibitor17139284 11752352 17016423
    MethyclothiazideMethychlothiazide (see all 6)135-07-9targetinhibitor17139284 11752352 17016423
    TorasemideTorasemida [INN-Spanish] (see all 3)56211-40-6targetinhibitor17460608 11752352 10406837

    3 IUPHAR Ligands for SLC12A1 (Kidney-specific Na-K-Cl symporter)    About this table
    LigandTypeActionAffinityPubmed IDs
    bumetanide
    InhibitorInhibition11882915
    piretanide
    InhibitorInhibition11882915
    furosemide
    InhibitorInhibition11882915

    Selected Novoseek inferred chemical compound relationships for SLC12A1 gene (see all 16)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    bumetanide 81.5 9 8384781 (2), 1506774 (1), 8498486 (1), 8743460 (1) (see all 8)
    chloride 70 15 1506774 (1), 17202415 (1), 17186942 (1), 8743460 (1) (see all 11)
    nacl 62.4 8 10486660 (1), 9587066 (1), 11133509 (1), 11496061 (1) (see all 7)
    86rb 60.3 1 8384781 (1)
    potassium 57.7 31 8384781 (2), 10617800 (1), 17202415 (1), 9355073 (1) (see all 21)
    furosemide 55.3 3 8743460 (1), 15564765 (1), 17460608 (1)
    sodium 54.7 19 11496061 (2), 17202415 (1), 16785747 (1), 15958043 (1) (see all 12)
    thiazide 54.4 3 15564765 (1), 14596636 (1)
    forskolin 41.3 1 7573487 (1)
    ammonium 24.2 1 12227253 (1)



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    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for SLC12A1 gene (2 alternative transcripts): 
    NM_000338.2  NM_001184832.1  

    Unigene Cluster for SLC12A1:

    Solute carrier family 12 (sodium/potassium/chloride transporters), member 1
    Hs.123116  [show with all ESTs]
    Unigene Representative Sequence: BX647067
    11 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000561127 ENST00000559641 ENST00000396577(uc010bem.3) ENST00000330289(uc010uex.2)
    ENST00000558405(uc010uew.1) ENST00000561031 ENST00000558252(uc001zwq.4)
    ENST00000560692(uc001zwr.4) ENST00000559723 ENST00000558805 ENST00000380993(uc001zwn.4)

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    Additional mRNA sequence: 

    AK129998.1 BC040138.2 BX647067.1 BX647484.1 EF559316.2 U58130.1 

    7 DOTS entries:

    DT.100016248  DT.107157  DT.95365788  DT.91695963  DT.101980929  DT.121081107  DT.91695960 

    Selected AceView cDNA sequences (see all 74):

    AB032525 AI792946 BE464188 AA746164 BG433923 AB032526 AI767758 BC040138 
    AB032527 AI631764 BX647484 BG428397 AI434839 AI498352 AW771529 AW271346 
    BG433644 U58130 BG430224 AI632015 NM_000338 BG425888 AI627643 AI913380 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for SLC12A1    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
    SP1:                                      -                                                                                                                     
    SP2:                                                                                                                                                            
    SP3:                    -           -     -                                                                                                                     

    ExUns: 24 ^ 25 ^ 26
    SP1:                  
    SP2:                  
    SP3:                  


    ECgene alternative splicing isoforms for SLC12A1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    SLC12A1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    SLC12A1 Expression
    About this image


    SLC12A1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Kidney (Urinary System)    fully expand to see all 2 entries
             Loop of Henle Cells Loop of Henle
             Metanephros
     
     Dermis (Integumentary System)    fully expand to see all 2 entries
             Zigzag Dermal Papilla Cells Dermal Papilla
     
     Epithelial Cells
             Loop of Henle Cells Loop of Henle
     
     Adipose (Muscoskeletal System)
             Mesenchymal Stem Cells Subcutaneous White Adipose
     
     Mesenchymal Stem Cells
             Mesenchymal Stem Cells Subcutaneous White Adipose
    SLC12A1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SLC12A1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.123116

    UniProtKB/Swiss-Prot: S12A1_HUMAN, Q13621
    Tissue specificity: Kidney specific

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for SLC12A1 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Slc12a11 , 5 solute carrier family 12, member 11, 5 88.77(n)1
    94.34(a)1
      2 (61.23 cM)5
    204951  NM_183354.21  NP_899197.21 
     1251525055 
    chicken
    (Gallus gallus)
    Aves SLC12A11 solute carrier family 12 (sodium/potassium/chloride more 79.52(n)
    83.64(a)
      415433  XM_004943799.1  XP_004943856.1 
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    Uncharacterized protein
    81(a)
    79(a)
    1 ↔ many
    1 ↔ many
    GL343561.1(360095-421979)
    GL343806.1(2696-17550)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia Str.121922 Transcribed sequence with moderate similarity to protein more 79.62(n)    BX706679.1 
    zebrafish
    (Danio rerio)
    Actinopterygii slc12a16
    solute carrier family 12, member 1
    67(a)
    1 ↔ 1
    18(4695727-4727527) ENSDARG00000059390
    fruit fly
    (Drosophila melanogaster)
    Insecta CG43573 sodium:chloride symporter 47(a)
    (best of 2)
      69B3   --
    worm
    (Caenorhabditis elegans)
    Secernentea F10E7.93
    nkcc-11
    bumetanide-sensitive Na-K-Cl
    cotransporter3
    nkcc-11
    25(a)3
    53.3(n)1
    48.19(a)1
      II(7106372-7107509)3
    35656481  NM_001268862.11  NP_001255791.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes --
    Putative ion transporter, similar to mammalian ele...
    21(a)
    1 → many
    II(686901-690263) YBR235W


    ENSEMBL Gene Tree for SLC12A1 (if available)
    TreeFam Gene Tree for SLC12A1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SLC12A1 gene
    SLC12A72  SLC12A32  SLC12A92  SLC12A62  SLC12A22  SLC12A82  SLC12A42  SLC12A52  
    6 SIMAP similar genes for SLC12A1 using alignment to 8 protein entries:     S12A1_HUMAN (see all proteins):
    NKCC2    SLC12A2    SLC12A3    SLC12A8    SLC12A6    SLC12A5

    Find genes that share paralogs with SLC12A1           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for SLC12A1 (see all 2099)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 15 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0102234
    Bartter syndrome 1 (BS1)4--see VAR_0102232 V F mis40--------
    VAR_0102244
    Bartter syndrome 1 (BS1)4--see VAR_0102242 D N mis40--------
    rs105623271,2
    C--25345344(+) gcctc-/AAA   
       
    /AAAA
    aaaaa
    4 -- int1 cds11NA 2
    rs1882765971,2
    --28562690(+) TTATTC/TTGGGT 2 -- us2k10--------
    rs1141094241,2
    F--28562894(+) CTCTAT/CTTCTG 2 -- us2k11Minor allele frequency- C:0.02WA 118
    rs763736561,2
    F--28562912(+) CTCACA/GACATT 2 -- us2k10--------
    rs726239701,2
    C--28563416(+) GGAAAT/CCACTT 2 -- us2k13Minor allele frequency- C:0.34CSA WA EA 239
    rs1811098701,2
    --28563427(+) AAATCA/GTTTCT 2 -- us2k10--------
    rs45472821,2
    C,F,H--28563488(+) CAGACC/TTGAGG 2 -- us2k119Minor allele frequency- T:0.02NS EA WA NA CSA 1462
    rs1421253611,2
    C--28563528(+) CTACTG/TGCAGA 2 -- us2k10--------

    HapMap Linkage Disequilibrium report for SLC12A1 (48483861 - 48596275 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 9 variations for SLC12A1:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2666859CNV Deletion23128226
    esv2474615CNV Deletion19546169
    esv2617587CNV Deletion19546169
    esv2749657CNV Deletion23290073
    nsv522923CNV Loss19592680
    nsv526690CNV Loss19592680
    esv7684CNV Loss19470904
    nsv904203CNV Gain21882294
    dgv746e1CNV Complex17122850

    Human Gene Mutation Database (HGMD): SLC12A1
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing SLC12A1
    DNA2.0 Custom Variant and Variant Library Synthesis for SLC12A1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600839   
    OMIM disorders: 601678  
    UniProtKB/Swiss-Prot: S12A1_HUMAN, Q13621
  • Bartter syndrome 1 (BS1) [MIM:601678]: An autosomal recessive disorder characterized by impaired salt
    reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis,
    and varying degrees of hypercalciuria. Bartter syndrome type 1 is a life-threatening condition beginning in
    utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a
    marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia.
    Note=The disease is caused by mutations affecting the gene represented in this entry

  • 8 diseases for SLC12A1:    
    About MalaCards
    bartter syndrome antenatal type 1    bartter syndrome, type 1    bartter syndrome, type 2    gitelman syndrome
    hypokalemia    diabetes insipidus    bartter disease    polyhydramnios

    6 diseases from the University of Copenhagen DISEASES database for SLC12A1:
    Bartter disease     Gitelman syndrome     Polyhydramnios     Nephrocalcinosis
    Hypokalemia     Nephrogenic diabetes insipidus

    Find genes that share disorders with SLC12A1           About GenesLikeMe

    Selected Novoseek inferred disease relationships for SLC12A1 gene (see all 19)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    bartters syndrome 95.9 44 9519207 (2), 9585600 (2), 15980941 (1), 19056867 (1) (see all 30)
    bartter syndrome, classic 94 2 11780689 (1), 15056980 (1)
    gitelman syndrome 91.4 5 15980941 (1), 12911530 (1), 10546515 (1), 15056980 (1)
    hyperprostaglandin e syndrome 91.3 2 9587066 (1), 17657111 (1)
    metabolic alkalosis 85.1 3 11826289 (1), 9672238 (1)
    nephrocalcinosis 79.8 2 9519207 (1), 19096086 (1)
    hypercalciuria 77.4 6 9519207 (2), 11815871 (1), 8841184 (1), 9672238 (1)
    hypokalemia 71.7 1 11815871 (1)
    diabetes insipidus nephrogenic 69.2 1 18216147 (1)
    alkalosis 65.9 4 11815871 (1), 8640224 (1), 8841184 (1)

    Genatlas disease: SLC12A1
    Bartter syndrome,hypokalemic,hypochloremic metabolic alkalosis with hyperkaliury,hyperexcretion of prostaglandin
    E,hyperreninemia hyperaldosteronism with normal blood pressure,insensitivity to AGT2,and hyperplasia of
    juxtaglomerular apparatus,autosomal recessive,presenting as an antenatal form with hydramnios prematurity and
    dehydration at built and a classic form with failure to thrive

    Genetic Association Database (GAD): SLC12A1
    Human Genome Epidemiology (HuGE) Navigator: SLC12A1 (10 documents)

    Export disorders for SLC12A1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for SLC12A1 gene, integrated from 10 sources (see all 182):
    (articles sorted by number of sources associating them with SLC12A1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Bartter's syndrome, hypokalemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. (PubMed id 8640224)1, 2, 3, 9 Simon D.B....Lifton R.P. (Nat. Genet. 1996)
    2. Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. (PubMed id 17460608)1, 4, 7, 9 Vormfelde S.V....BrockmAPller J. (Clin. Pharmacol. Ther. 2007)
    3. Interaction of alpha(1)-Na,K-ATPase and Na,K,2Cl-cotransporter genes in human essential hypertension. (PubMed id 11509477)1, 4, 9 Glorioso N....Ruiz-Opazo N. (Hypertension 2001)
    4. Non-association of the thiazide-sensitive Na,Cl-cotransporter gene with polygenic hypertension in both rats and humans. (PubMed id 11564973)1, 4, 9 Song Y....Ruiz-Opazo N. (J. Hypertens. 2001)
    5. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. (PubMed id 18391953)1, 4, 9 Ji W....Lifton R.P. (Nat. Genet. 2008)
    6. Similar Effects of all WNK3 Variants upon SLC12 Cotransporters. (PubMed id 21613606)1, 2 Cruz-Rangel S.... Mercado A. (Am. J. Physiol. 2011)
    7. L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms. (PubMed id 20424473)1, 4 Yokoyama K....Hosoya T. (Nephron Clin Pract 2010)
    8. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)
    9. Allelic-based gene-gene interaction associated with quantitative traits. (PubMed id 19058262)1, 4 Jung J....Foroud T.M. (Genet. Epidemiol. 2009)
    10. Late-onset manifestation of antenatal Bartter syndrome as a result of residual function of the mutated renal Na+-K+-2Cl- co-transporter. (PubMed id 16807401)1, 7 Pressler C.A....Waldegger S. (J. Am. Soc. Nephrol. 2006)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 6557 HGNC: 10910 AceView: SLC12A1 Ensembl:ENSG00000074803 euGenes: HUgn6557
    ECgene: SLC12A1 H-InvDB: SLC12A1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for SLC12A1 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for SLC12A1 gene:
    Search GeneIP for patents involving SLC12A1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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