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Available structures
PDB Ortholog search: PDBe RCSB
Aliases WNK4, PHA2B, PRKWNK lysine deficient protein kinase 4
External IDs MGI: 1917097 HomoloGene: 13020 GeneCards: WNK4
Gene location (Human)
Chromosome 17 (human)
Chr. Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for WNK4
Genomic location for WNK4
Band 17q21.2 Start 42,780,678 bp[1]
End 42,796,936 bp[1]
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 17: 42.78 – 42.8 Mb Chr 11: 101.26 – 101.28 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Serine/threonine-protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4 gene.[5]


The WNK4 gene encodes a serine-threonine kinase expressed in distal nephron.[5] Its primary role in renal physiology is as a molecular switch between the angiotensin IIaldosterone mediated volume retention and the aldosterone mediated potassium wasting. This is achieved by regulating the sodium-chloride symporter (NCC), that is uniquely expressed in the distal nephron and is sensitive to thiazide type diuretics.[6]

Under basal conditions (low circulating Ang II and low Aldosterone), WNK4 will inhibit NCC function. It has been proposed that in the event of hyperkalemia and an increased secretion of aldosterone (which will upregulate both ENac and ROMK), this inhibition of NCC, will allow an increase in the arrival of sodium to the distal nephron (rich in ENaC and ROMK) which will allow the exchange of sodium for potassium ions, thereby reducing plasma potassium levels, without increasing sodium chloride retention (which is always accompanied by volume expansion). Furthermore, it has been proposed that in the presence of AngII the WNK4 mediated NCC inhibition will be suppressed thereby increasing sodium-chloride reabsorption in the distal convoluted tubule. This along with the concomitant increase in passive water reabsortion due to the increased salt load in the distal convluted tubule cells will ultimately increase circulating volume.[7]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000126562 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035112 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b "Entrez Gene: WNK4 WNK lysine deficient protein kinase 4". 
  6. ^ San-Cristobal P, de los Heros P, Ponce-Coria J, Moreno E, Gamba G (2008). "WNK kinases, renal ion transport and hypertension". Am. J. Nephrol. 28 (5): 860–70. doi:10.1159/000139639. PMC 2820349Freely accessible. PMID 18547946. 
  7. ^ San-Cristobal P, Pacheco-Alvarez D, Richardson C, Ring AM, Vazquez N, Rafiqi FH, Chari D, Kahle KT, Leng Q, Bobadilla NA, Hebert SC, Alessi DR, Lifton RP, Gamba G (March 2009). "Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway". Proc. Natl. Acad. Sci. U.S.A. 106 (11): 4384–9. doi:10.1073/pnas.0813238106. PMC 2647339Freely accessible. PMID 19240212. 

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