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WNK lysine deficient protein kinase 4
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols WNK4 ; PHA2B; PRKWNK4
External IDs OMIM601844 MGI1917097 HomoloGene13020 ChEMBL: 1795196 GeneCards: WNK4 Gene
EC number
Species Human Mouse
Entrez 65266 69847
Ensembl ENSG00000126562 ENSMUSG00000035112
UniProt Q96J92 Q80UE6
RefSeq (mRNA) NM_032387 NM_175638
RefSeq (protein) NP_115763 NP_783569
Location (UCSC) Chr 17:
42.78 – 42.8 Mb
Chr 11:
101.26 – 101.28 Mb
PubMed search [1] [2]

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.[1]


The WNK4 gene encodes a serine-threonine kinase expressed in distal nephron.[1] Its primary role in renal physiology is as a molecular switch between the angiontensin 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.[2]

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.[3]


  1. ^ a b "Entrez Gene: WNK4 WNK lysine deficient protein kinase 4". 
  2. ^ 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 2820349. PMID 18547946. 
  3. ^ 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 2647339. PMID 19240212. 

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