Human Gene WNK4 (ENST00000246914.10) from GENCODE V44
  Description: Homo sapiens WNK lysine deficient protein kinase 4 (WNK4), transcript variant 1, mRNA. (from RefSeq NM_032387)
RefSeq Summary (NM_032387): This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009].
Gencode Transcript: ENST00000246914.10
Gencode Gene: ENSG00000126562.17
Transcript (Including UTRs)
   Position: hg38 chr17:42,780,610-42,797,066 Size: 16,457 Total Exon Count: 19 Strand: +
Coding Region
   Position: hg38 chr17:42,780,699-42,796,688 Size: 15,990 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:42,780,610-42,797,066)mRNA (may differ from genome)Protein (1243 aa)
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HGNCHPRDLynxMalacardsMGImyGene2
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: WNK4_HUMAN
DESCRIPTION: RecName: Full=Serine/threonine-protein kinase WNK4; EC=2.7.11.1; AltName: Full=Protein kinase lysine-deficient 4; AltName: Full=Protein kinase with no lysine 4;
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, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium (By similarity).
ENZYME REGULATION: Activation requires autophosphorylation of Ser- 335. Phosphorylation of Ser-331 also promotes increased activity (By similarity).
SUBUNIT: Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By similarity).
SUBCELLULAR LOCATION: Cell junction, tight junction (By similarity). Note=Present exclusively in intercellular junctions in the distal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical collecting duct. WNK4 is part of the tight junction complex (By similarity).
TISSUE SPECIFICITY: Expressed in kidney, colon and skin.
PTM: Phosphorylated by WNK1 and WNK3 (By similarity).
DISEASE: Defects in WNK4 are a cause of pseudohypoaldosteronism type 2B (PHA2B) [MIM:614491]. PHAII is an autosomal dominant disease characterized by severe hypertension, hyperkalemia, and sensitivity to thiazide diuretics which may result from a chloride shunt in the renal distal nephron.
SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.
SIMILARITY: Contains 1 protein kinase domain.
CAUTION: Cys-203 is present instead of the conserved Lys which is expected to be an active site residue. Lys-186 appears to fulfill the required catalytic function.
SEQUENCE CAUTION: Sequence=BAC04669.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAC48387.1; Type=Frameshift; Positions=4;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/WNK4";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: WNK4
Diseases sorted by gene-association score: pseudohypoaldosteronism, type iib* (1669), pseudohypoaldosteronism, type iie* (50), pseudohypoaldosteronism (49), arthrogryposis, distal, type 3 (15), metabolic acidosis (12), pseudohyperkalemia, familial, 2, due to red cell leak (10), renal tubular transport disease (8), familial hypertension (6), hypertension, essential (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.35 RPKM in Kidney - Cortex
Total median expression: 49.13 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -30.3089-0.340 Picture PostScript Text
3' UTR -117.60378-0.311 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR024678 - Kinase_OSR1/WNK_CCT
IPR000719 - Prot_kinase_cat_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF12202 - Oxidative-stress-responsive kinase 1 C-terminal domain
PF00069 - Protein kinase domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2V3S - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q96J92
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
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Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019869 chloride channel inhibitor activity

Biological Process:
GO:0006468 protein phosphorylation
GO:0006811 ion transport
GO:0006821 chloride transport
GO:0008104 protein localization
GO:0010766 negative regulation of sodium ion transport
GO:0016310 phosphorylation
GO:0035556 intracellular signal transduction
GO:0050794 regulation of cellular process
GO:0050801 ion homeostasis
GO:0070294 renal sodium ion absorption
GO:0072156 distal tubule morphogenesis
GO:0090188 negative regulation of pancreatic juice secretion

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005923 bicellular tight junction
GO:0016020 membrane
GO:0030054 cell junction


-  Descriptions from all associated GenBank mRNAs
  AF390018 - Homo sapiens putative protein kinase WNK4 (PRKWNK4) mRNA, complete cds.
BC136664 - Homo sapiens WNK lysine deficient protein kinase 4, mRNA (cDNA clone MGC:168277 IMAGE:9020654), complete cds.
BC144356 - Homo sapiens cDNA clone IMAGE:9052877, with apparent retained intron.
AJ316534 - Homo sapiens mRNA for serine/threonine protein kinase (PRKWNK4 gene).
JD166902 - Sequence 147926 from Patent EP1572962.
AJ309861 - Homo sapiens partial mRNA for putative protein kinase WNK4 (PRKWNK4 gene).
AK096052 - Homo sapiens cDNA FLJ38733 fis, clone KIDNE2010762, moderately similar to Rattus norvegicus protein kinase WNK1 (WNK1) mRNA.
AK301963 - Homo sapiens cDNA FLJ52922 complete cds, highly similar to Serine/threonine-protein kinase WNK4 (EC 2.7.11.1).
AK096003 - Homo sapiens cDNA FLJ38684 fis, clone KIDNE2000801.
JD310099 - Sequence 291123 from Patent EP1572962.

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000246914.1, ENST00000246914.2, ENST00000246914.3, ENST00000246914.4, ENST00000246914.5, ENST00000246914.6, ENST00000246914.7, ENST00000246914.8, ENST00000246914.9, NM_032387, PRKWNK4, Q8N8X3, Q8N8Z2, Q96DT8, Q96J92, Q9BYS5, uc002ibj.1, uc002ibj.2, uc002ibj.3, uc002ibj.4, uc002ibj.5, WNK4_HUMAN
UCSC ID: ENST00000246914.10
RefSeq Accession: NM_032387
Protein: Q96J92 (aka WNK4_HUMAN)
CCDS: CCDS11439.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene WNK4:
pha2 (Pseudohypoaldosteronism Type II)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.