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WNK1 Gene

protein-coding   GIFtS: 65
GCID: GC12P000862

WNK Lysine Deficient Protein Kinase 1

(Previous names: protein kinase, lysine deficient 1, hereditary sensory neuropathy,...)
(Previous symbols: PRKWNK1, HSN2)
  See WNK1-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
WNK Lysine Deficient Protein Kinase 11 2     PSK2
HSN21 2 3 5     Prostate-Derived Sterile 20-Like Kinase2
PRKWNK11 2 3 5     Serine/Threonine-Protein Kinase WNK12
KDP2 3 5     WNK Lysine Deficient Protein Kinase 1 Isoform2
Erythrocyte 65 KDa Protein2 3     KIAA03443
Protein Kinase With No Lysine 12 3     hWNK13
p652 3     Kinase Deficient Protein3
EC 2.7.11.13 8     Protein Kinase Lysine-Deficient 13
HSAN22 5     PHA2C5
Hereditary Sensory Neuropathy, Type II1     EC 2.7.118
Protein Kinase, Lysine Deficient 11     

External Ids:    HGNC: 145401   Entrez Gene: 651252   Ensembl: ENSG000000602377   OMIM: 6052325   UniProtKB: Q9H4A33   

Export aliases for WNK1 gene to outside databases

Previous GC identifer: GC12P000733


(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 WNK1 Gene:
This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a
key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene
have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II.
Alternatively spliced transcript variants encoding different isoforms have been described but the full-length
nature of all of them has yet to be determined.(provided by RefSeq, May 2010)

GeneCards Summary for WNK1 Gene:
WNK1 (WNK lysine deficient protein kinase 1) is a protein-coding gene. Diseases associated with WNK1 include hereditary sensory and autonomic neuropathy type iia, and hereditary sensory and autonomic neuropathy type ii. GO annotations related to this gene include protein kinase inhibitor activity and protein serine/threonine kinase activity. An important paralog of this gene is WNK4.

UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3
Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell
signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride
cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and
SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating
the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity
of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin
cytoskeletal reorganization. Phosphorylates NEDD4L

Gene Wiki entry for WNK1 Gene


(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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Regulatory elements:
   Regulatory transcription factor binding sites in the WNK1 gene promoter:
         Pax-5   AP-1   AP-2alpha isoform 3   ATF-2   AP-2alpha isoform 2   LCR-F1   AP-2alpha isoform 4   c-Jun   AP-2alpha   AP-2alphaA   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidWNK1 promoter sequence
   Search Chromatin IP Primers for WNK1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat WNK1


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

Entrez Gene cytogenetic band: 12p13.3   Ensembl cytogenetic band:  12p13.33   HGNC cytogenetic band: 12p13.3

WNK1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
WNK1 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12P000862:  view genomic region     (about GC identifiers)

Start:
861,759 bp from pter      End:
1,020,618 bp from pter
Size:
158,860 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: WNK1_HUMAN, Q9H4A3 (See protein sequence)
Recommended Name: Serine/threonine-protein kinase WNK1  
Size: 2382 amino acids; 250794 Da
Cofactor: Magnesium
Subunit: Interacts with SYT2 (By similarity). Interacts with WNK3 and WNK4 (By similarity). Interacts with KLHL3
Caution: PubMed:2507249 describes a peptide sequence containing a GlcNAc glycosylated Ser in position 164 while it
is an Arg residue according to others
Caution: Cys-250 is present instead of the conserved Lys which is expected to be an active site residue. Lys-233
appears to fulfill the required catalytic function
Caution: HSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron. It has been shown
to be a nervous system-specific exon of WNK1 included in isoform 4 and isoform 5 (PubMed:18521183)
Caution: It is uncertain whether Met-1 or Met-214 is the initiator in isoform 4 and isoform 5
Sequence caution: Sequence=AAF31483.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of
unknown origin in the C-terminal part; Sequence=AAI30468.1; Type=Miscellaneous discrepancy; Note=Probable cloning
artifact; Sequence=AAI30470.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;
Sequence=DAA04494.1; Type=Erroneous gene model prediction; Note=Includes 3' and 3' intronic sequences;
Secondary accessions: A1L4B0 C5HTZ5 C5HTZ6 C5HTZ7 H6WZW3 O15052 P54963 Q4VBX9 Q6IFS5 Q86WL5
Q8N673 Q96CZ6 Q9P1S9
Alternative promoter usage, Alternative splicing: 6 isoforms:  Q9H4A3-1   Q9H4A3-2   Q9H4A3-4   Q9H4A3-5   Q9H4A3-6   Q9H4A3-7   (Contains the nervous system-specific exon HSN2. Produced by alternative splicing)

Explore the universe of human proteins at neXtProt for WNK1: NX_Q9H4A3

Explore proteomics data for WNK1 at MOPED

Post-translational modifications: 

  • O-glycosylated1
  • Ubiquitinated in vitro by the BCR(KLHL3) complex; additional evidences are required in vivo1
  • Ubiquitination2 at Lys375
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for WNK1 (Q9H4A3) (see all 19)
     PLLPQVP  EIGRGSF  YDESVDV  EYPYSEC 


    See WNK1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_001171914.1  NP_055638.2  NP_061852.3  NP_998820.3  

    ENSEMBL proteins: 
     ENSP00000441972   ENSP00000313059   ENSP00000392542   ENSP00000438313   ENSP00000446462  
     ENSP00000439552   ENSP00000460651   ENSP00000459380   ENSP00000446253   ENSP00000437503  
     ENSP00000438985   ENSP00000444465   ENSP00000433548   ENSP00000341292  
    Reactome Protein details: Q9H4A3

    WNK1 Human Recombinant Protein Products:

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    OriGene Protein Over-expression Lysate for WNK1
    OriGene Custom MassSpec
    OriGene Custom Protein Services for WNK1
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    Novus Biologicals WNK1 Proteins
    Novus Biologicals WNK1 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for WNK1

     
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    EMD Millipore Mono- and Polyclonal Antibodies for the study of WNK1
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    WNK1 Assay Products:

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    Cloud-Clone Corp. ELISAs for WNK1
    Cloud-Clone Corp. CLIAs for WNK1
    Search eBioscience for ELISAs for WNK1 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: WNK lysine deficient protein kinase 1
    Wnk family

    4 InterPro protein domains:
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS
     IPR000719 Prot_kinase_dom
     IPR024678 Kinase_OSR1/WNK_CCT

    Graphical View of Domain Structure for InterPro Entry Q9H4A3

    ProtoNet protein and cluster: Q9H4A3

    UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3
    Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily
    Similarity: Contains 1 protein kinase domain


    Find genes that share domains with WNK1           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: WNK1_HUMAN, Q9H4A3
    Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell
    signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride
    cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and
    SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating
    the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity
    of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin
    cytoskeletal reorganization. Phosphorylates NEDD4L
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: By hypertonicity. Activation requires autophosphorylation of Ser-382. Phosphorylation of
    Ser-378 also promotes increased activity (By similarity)

         Enzyme Numbers (IUBMB): EC 2.7.11.11 2 EC 2.7.112

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004674protein serine/threonine kinase activity IDA10660600
    GO:0004713protein tyrosine kinase activity ----
    GO:0004860protein kinase inhibitor activity IEA--
    GO:0005515protein binding IPI15350218
         
    Find genes that share ontologies with WNK1           About GenesLikeMe


    Phenotypes:
         6 GenomeRNAi human phenotypes for WNK1:
     Decreased Tat-dependent transc  Decreased p24 protein expressi  Decreased substrate adherent c  Decreased viability with pacli 
     Increased cell death HMECs cel  Upregulation of Wnt/beta-caten 

         9 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Wnk1):
     cardiovascular system  embryogenesis  growth/size/body  hematopoietic system  homeostasis/metabolism 
     mortality/aging  muscle  nervous system  renal/urinary system 

    Find genes that share phenotypes with WNK1           About GenesLikeMe

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for WNK1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for WNK1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for WNK1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for WNK1

    miRNA
    Products:
        
    miRTarBase miRNAs that target WNK1:
    hsa-mir-877-3p (MIRT037011), hsa-mir-378a-3p (MIRT043954), hsa-mir-149-5p (MIRT045660), hsa-mir-93-3p (MIRT038785), hsa-mir-615-3p (MIRT040135), hsa-mir-192-5p (MIRT005582), hsa-mir-550a-5p (MIRT037785), hsa-let-7b-5p (MIRT052359), hsa-mir-18a-3p (MIRT040788), hsa-mir-320a (MIRT044712), hsa-mir-331-3p (MIRT043274), hsa-mir-125b-5p (MIRT046056), hsa-mir-197-3p (MIRT048089), hsa-mir-183-5p (MIRT047108), hsa-mir-186-5p (MIRT045005), hsa-mir-21-5p (MIRT030974), hsa-mir-215-5p (MIRT005583), hsa-mir-106b-3p (MIRT038570), hsa-mir-193b-3p (MIRT041474), hsa-mir-423-3p (MIRT042524)

    Block miRNA regulation of human, mouse, rat WNK1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate WNK1 (see all 115):
    hsa-miR-300 hsa-miR-199a-3p hsa-miR-4272 hsa-miR-106a hsa-miR-4305 hsa-miR-128 hsa-miR-3074-3p hsa-miR-1244
    SwitchGear 3'UTR luciferase reporter plasmidWNK1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat WNK1

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector (see all 4): WNK1 (NM_001184985)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for WNK1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat WNK1
    Addgene plasmids for WNK1 

    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for WNK1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for WNK1


    (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
    WNK1_HUMAN, Q9H4A3: Cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol2
    nucleus2
    plasma membrane2
    peroxisome1

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IDA10660600

    Find genes that share ontologies with WNK1           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 WNK1 About    
    See pathways by source

    SuperPathContained pathways About
    1Ion channel transport
    Ion channel transport0.58
    Stimuli-sensing channels0.58
    2Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds
    Transmembrane transport of small molecules0.47
    3PI3K / Akt Signaling
    PI3K / Akt Signaling
    4EGFR1 Signaling Pathway
    EGFR1 Signaling Pathway
    5Diuretics Pathway, Pharmacodynamics
    Diuretics Pathway, Pharmacodynamics


    Find genes that share SuperPaths with WNK1           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    3 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for WNK1
        MAPK Signaling
    Akt Signaling
    ERK5 Signaling

    1 Cell Signaling Technology (CST) Pathway for WNK1
        PI3K / Akt Signaling

    1 BioSystems Pathway for WNK1
        EGFR1 Signaling Pathway

    1 Reactome Pathway for WNK1
        Stimuli-sensing channels

    1 PharmGKB Pathway for WNK1
        Diuretics Pathway, Pharmacodynamics

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for WNK1
    Interactions:

        GeneGlobe Interaction Network for WNK1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for WNK1 (Q9H4A31, 2, 3 ENSP000003130594) via UniProtKB, MINT, STRING, and/or I2D (see all 211)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    OXSR1O957471, 2, 3, ENSP000003117134EBI-457907,EBI-620853 MINT-5207758 MINT-5207733 I2D: score=3 STRING: ENSP00000311713
    GLIS2Q9BZE02, 3, ENSP000002623664MINT-4651487 I2D: score=2 STRING: ENSP00000262366
    ABCF1Q8NE713I2D: score=2 
    ENSG00000206427P486343I2D: score=2 
    ENSG00000206490Q8NE713I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003084positive regulation of systemic arterial blood pressure IEA--
    GO:0006468protein phosphorylation IDA10660600
    GO:0006811ion transport ISS--
    GO:0010923negative regulation of phosphatase activity IDA19389623
    GO:0035556intracellular signal transduction IDA10660600

    Find genes that share ontologies with WNK1           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 

    Browse Tocris compounds for WNK1

    5 HMDB Compounds for WNK1    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    ChlorineCl2 (see all 13)16887-00-6--
    MagnesiumMagnesium (see all 2)7439-95-4--
    SodiumSodium (see all 2)7440-23-5--

    Selected Novoseek inferred chemical compound relationships for WNK1 gene (see all 15)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    lysine 73.6 23 11571656 (1), 16083423 (1), 16081417 (1), 19609280 (1) (see all 13)
    thiazide 72 2 16172412 (1), 18270262 (1)
    threonine 65 8 16081417 (1), 19347040 (1), 19609280 (1), 18433299 (1) (see all 6)
    potassium 61.1 20 19609280 (3), 16709664 (3), 18695394 (1), 16820787 (1) (see all 11)
    chloride 55 6 16949040 (5), 17194447 (1)
    serine 52.5 10 16263722 (2), 16083423 (1), 19347040 (1), 19609280 (1) (see all 6)
    sodium 51.3 13 19609280 (3), 16006511 (2), 18591455 (2), 18695394 (1) (see all 8)
    nacl 45.8 4 15841204 (2), 16820787 (1), 20375989 (1)
    proline 43.6 4 16083423 (1), 16173916 (1), 17190791 (1)
    wortmannin 18.6 2 15799971 (1), 14611643 (1)

    1 PharmGKB related drug/compound annotation for WNK1 gene    About this table
    Drug/compound PharmGKB Annotation
    hydrochlorothiazideCA  



    Find genes that share compounds with WNK1           About GenesLikeMe



    (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 WNK1 gene (4 alternative transcripts): 
    NM_001184985.1  NM_014823.2  NM_018979.3  NM_213655.4  

    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 21):
    ENST00000535572 ENST00000315939(uc001qio.4 uc001qip.4) ENST00000447667(uc001qin.3)
    ENST00000540360 ENST00000538787 ENST00000544965 ENST00000545285 ENST00000535698
    ENST00000574564(uc001qiq.3) ENST00000574679 ENST00000542543 ENST00000545055
    ENST00000534872 ENST00000542424 ENST00000537603(uc009zdn.1) ENST00000544559
    ENST00000543065(uc009zdm.1) ENST00000540885
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate WNK1 (see all 115):
    hsa-miR-300 hsa-miR-199a-3p hsa-miR-4272 hsa-miR-106a hsa-miR-4305 hsa-miR-128 hsa-miR-3074-3p hsa-miR-1244
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    GenScript: all cDNA clones in your preferred vector (see all 4): WNK1 (NM_001184985)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat WNK1
    Addgene plasmids for WNK1 
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      QuantiTect SYBR Green Assays in human, mouse, rat WNK1
      QuantiFast Probe-based Assays in human, mouse, rat WNK1

    Selected AceView cDNA sequences (see all 695):

    AI149474 AW967056 AW295073 CA952889 BM715888 AI697129 AI313426 CK724903 
    AA393667 W74493 AI492425 BC013629 AI492452 AI804294 AI374806 AA705259 
    AA603085 AA234119 BU739794 BC044600 AA587555 BQ717639 BF115281 AA700748 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for WNK1 (see all 8)    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14a · 14b ^ 15a · 15b ^ 16 ^ 17 ^ 18 ^ 19 ^
    SP1:                                -           -                                         -                       -                                             
    SP2:                                -           -                                         -           -     -     -                                             
    SP3:                                                                                                                                                            
    SP4:                                                                                                  -     -     -                                             
    SP5:                                                                                                                                                            

    ExUns: 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25a · 25b ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29a · 29b
    SP1:                                                        -     -                     
    SP2:                                                        -     -                     
    SP3:                                                                                    
    SP4:                                                                                    
    SP5:                                                                                    


    ECgene alternative splicing isoforms for WNK1

    (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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    WNK1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CAGCACATTA
    WNK1 Expression
    About this image


    WNK1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 16) fully expand
     
     Brain (Nervous System)    fully expand to see all 7 entries
             Cerebral Cortex
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Metencephalon
     
     Eye (Sensory Organs)    fully expand to see all 2 entries
             Retina
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
     
     Kidney (Urinary System)
             Distal Tubule Cells Distal Tubule
    WNK1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    WNK1 Protein Expression

    UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3
    Tissue specificity: Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal
    muscle. Isoform 3 is kidney-specific and specifically expressed in the distal convoluted tubule (DCT) and
    connecting tubule (CNT) of the nephron

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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 eukaryotes.

    Orthologs for WNK1 gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Wnk11 , 5 WNK lysine deficient protein kinase 11, 5 86.87(n)1
    86.11(a)1
      6 (56.86 cM)5
    2323411  NM_001199084.11  NP_001186013.11 
     1199239695 
    chicken
    (Gallus gallus)
    Aves WNK16
    WNK lysine deficient protein kinase 1
    68(a)
    1 ↔ 1
    1(60573792-60671286)
    lizard
    (Anolis carolinensis)
    Reptilia WNK16
    WNK lysine deficient protein kinase 1
    55(a)
    1 ↔ 1
    5(12207683-12335637)
    African clawed frog
    (Xenopus laevis)
    Amphibia BJ089983.12   -- 75.66(n)    BJ089983.1 
    zebrafish
    (Danio rerio)
    Actinopterygii 570902542   -- 79.71(n)    57090254 
    fruit fly
    (Drosophila melanogaster)
    Insecta Wnk6
    --
    23(a)
    1 → many
    3L(21536950-21548028)
    worm
    (Caenorhabditis elegans)
    Secernentea wnk-16
    Protein WNK-1, isoform l (wnk-1) mRNA, complete cd...
    26(a)
    1 → many
    IV(9200116-9212232) WBGene00006941
    Alicante grape
    (Vitis vinifera)
    eudicotyledons CB006804.12   -- 71.81(n)    CB006804.1 


    ENSEMBL Gene Tree for WNK1 (if available)
    TreeFam Gene Tree for WNK1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for WNK1 gene
    WNK42  WNK22  NRBP12  NRBP22  WNK32  
    17 SIMAP similar genes for WNK1 using alignment to 19 protein entries:     WNK1_HUMAN (see all proteins):
    CAMK2A    BRAF    STK11    MST094    NEK9    STK25
    CDK4    NEK6    DKFZp564L2416    STK36    PAK2    STK17A
    WNK2    WNK4    DAPK1    MAP4K5    ZAK

    Find genes that share paralogs with WNK1           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 WNK1 (see all 3510)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0413214
    A lung adenocarcinoma sample4--see VAR_0413212 F L mis40--------
    VAR_0356404
    A colorectal cancer sample4--see VAR_0356402 E G mis40--------
    VAR_0356414
    Breast cancer samples4--see VAR_0356412 Q E mis40--------
    VAR_0413114
    A breast pleomorphic lobular carcinoma sample4--see VAR_0413112 E Q mis40--------
    VAR_0413204
    A breast pleomorphic lobular carcinoma sample4--see VAR_0413202 S C mis40--------
    rs1110335921,2
    Cpathogenic1914610(+) ACTTCC/TAACCC 6 Q * stg1 int10--------
    rs1110335911,2
    Cpathogenic1915261(+) TTTACC/TGAAAT 6 R * stg1 int10--------
    rs1110335901,2
    Cpathogenic1915336(+) ACTTGC/TAGCCT 6 Q * stg1 int10--------
    rs123223521,2
    F--797309(+) ATGTTC/TGTAAC 4 -- us2k11Minor allele frequency- T:0.02WA 118
    rs1824480651,2
    --797379(+) TGTAGC/TTTGTG 4 -- us2k10--------

    HapMap Linkage Disequilibrium report for WNK1 (861759 - 1020618 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for WNK1 (see all 28):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2745368CNV Deletion23290073
    nsv821212CNV Deletion20802225
    dgv27e180CNV Deletion20482838
    dgv254e199CNV Deletion23128226
    esv2745369CNV Deletion23290073
    esv2422082CNV Deletion20811451
    esv269252CNV Insertion20981092
    nsv898576CNV Loss21882294
    nsv518946CNV Loss19592680
    nsv898577CNV Loss21882294

    Human Gene Mutation Database (HGMD): WNK1
    Locus Specific Mutation Databases (LSDB): WNK1

    Site Specific Mutation Identification with PCR Assays
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    (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: 605232   
    OMIM disorders: 614492  201300  
    UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3
  • Pseudohypoaldosteronism 2C (PHA2C) [MIM:614492]: An autosomal dominant disorder characterized by severe
    hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction
    of physiologic abnormalities by thiazide diuretics. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Neuropathy, hereditary sensory and autonomic, 2A (HSAN2A) [MIM:201300]: A form of hereditary sensory and
    autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration
    of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an
    autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of
    symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers,
    and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper
    limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal
    autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with
    decreased numbers of unmyelinated fibers in sural nerves. Note=The disease is caused by mutations affecting the
    gene represented in this entry

  • 11 diseases for WNK1:    
    About MalaCards
    hereditary sensory and autonomic neuropathy type iia    hereditary sensory and autonomic neuropathy type ii    pseudohypoaldosteronism type iic    avascular necrosis of the femoral head
    pseudohypoaldosteronism type ii    pseudohypoaldosteronism    otospondylomegaepiphyseal dysplasia    hereditary sensory neuropathy
    neuropathy    autonomic neuropathy    gitelman syndrome

    4 diseases from the University of Copenhagen DISEASES database for WNK1:
    Pseudohypoaldosteronism     Hypertension     Peripheral neuropathy     Gitelman syndrome

    Find genes that share disorders with WNK1           About GenesLikeMe

    8 Novoseek inferred disease relationships for WNK1 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pseudohypoaldosteronism 96.7 25 16006511 (2), 16081417 (1), 16709664 (1), 15686619 (1) (see all 22)
    gordon syndrome 94.3 11 17957199 (2), 15888480 (2), 16709664 (1), 18277144 (1) (see all 8)
    hyperkalemia 83.6 19 17957199 (2), 18550644 (2), 12522152 (2), 18695394 (1) (see all 15)
    genetic hypertension 57.5 3 15309683 (1), 16501604 (1)
    essential hypertension 55.6 5 19347040 (1), 18547946 (1), 18277144 (1), 15888480 (1)
    hypertension arterial 32.3 2 18701621 (1), 14645531 (1)
    hypotension 8.14 2 15309683 (1)
    cancer 0 2 17667937 (1), 20094755 (1)

    Genetic Association Database (GAD): WNK1
    Human Genome Epidemiology (HuGE) Navigator: WNK1 (16 documents)

    Export disorders for WNK1 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 WNK1 gene, integrated from 10 sources (see all 178):
    (articles sorted by number of sources associating them with WNK1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion. (PubMed id 19347040)1, 4, 9 Newhouse S....Munroe P.B. (PLoS ONE 2009)
    2. Variations in the WNK1 gene modulates the effect of dietary intake of sodium and potassium on blood pressure determination. (PubMed id 19609280)1, 4, 9 Osada Y....Yamakawa-Kobayashi K. (J. Hum. Genet. 2009)
    3. Common variation in the WNK1 gene and blood pressure in childhood: the Avon Longitudinal Study of Parents and Children. (PubMed id 18809789)1, 4, 9 Tobin M.D....Burton P.R. (Hypertension 2008)
    4. Multiple promoters in the WNK1 gene: one controls expression of a kidney-specific kinase-defective isoform. (PubMed id 14645531)1, 2, 9 Delaloy C.... Jeunemaitre X. (Mol. Cell. Biol. 2003)
    5. WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. (PubMed id 11571656)1, 2, 9 Verissimo F. and Jordan P. (Oncogene 2001)
    6. Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulation. (PubMed id 18591455)1, 4, 9 Manunta P....Samani N.J. (Hypertension 2008)
    7. Human hypertension caused by mutations in WNK kinases. (PubMed id 11498583)1, 2, 9 Wilson F.H.... Lifton R.P. (Science 2001)
    8. WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. (PubMed id 16172412)1, 4, 9 Turner S.T....Boerwinkle E. (Hypertension 2005)
    9. Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. (PubMed id 23576762)1, 2 Shibata S....Lifton R.P. (Proc. Natl. Acad. Sci. U.S.A. 2013)
    10. The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. (PubMed id 23387299)1, 2 Ohta A....Kurz T. (Biochem. J. 2013)

    (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: 65125 HGNC: 14540 AceView: PRKWNK1 Ensembl:ENSG00000060237 euGenes: HUgn65125
    ECgene: WNK1 H-InvDB: WNK1

    (According to HUGE)
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    HUGE: KIAA0344

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for WNK1 Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=WNK1[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for WNK1 gene:
    Search GeneIP for patents involving WNK1

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



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