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Gene Review

WNK3  -  WNK lysine deficient protein kinase 3

Homo sapiens

Synonyms: KIAA1566, PRKWNK3, Protein kinase lysine-deficient 3, Protein kinase with no lysine 3, Serine/threonine-protein kinase WNK3
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Disease relevance of WNK3


High impact information on WNK3

  • Here, we show that WNK3 completely prevents the cell swelling-induced activation of KCC1-KCC4 in Xenopus oocytes [3].
  • Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway [4].
  • Suppression of endogenous WNK3 protein by RNA interference accelerates the apoptotic response and promotes the activation of caspase-3 [4].
  • Endogenous WNK3 protein is an active protein kinase when immunoprecipitated from cells and its overexpression increases the survival of HeLa cells by delaying the onset of apoptosis [4].
  • However, additional co-expression studies in oocytes revealed WNK3 inhibited the renal-specific K+ channel ROMK1 activity greater than 5.5-fold (p < .0001) by altering its plasmalemmal surface expression; WNK3 did not affect ROMK1's conductance or open/closed probability [2].

Biological context of WNK3


Associations of WNK3 with chemical compounds

  • WNK3 did not alter paracellular Cl- flux in tetracycline-responsive MDCK II cells, nor affect amiloride-sensitive currents when co-expressed with ENaC in Xenopus laevis oocytes [2].

Other interactions of WNK3

  • The predicted WNK3 protein has a similar structural organization to the other human WNK kinases [1].


  1. Cloning, genomic organization, alternative splicing and expression analysis of the human gene WNK3 (PRKWNK3). Holden, S., Cox, J., Raymond, F.L. Gene (2004) [Pubmed]
  2. WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1). Leng, Q., Kahle, K.T., Rinehart, J., MacGregor, G.G., Wilson, F.H., Canessa, C.M., Lifton, R.P., Hebert, S.C. J. Physiol. (Lond.) (2006) [Pubmed]
  3. WNK3 bypasses the tonicity requirement for K-Cl cotransporter activation via a phosphatase-dependent pathway. de Los Heros, P., Kahle, K.T., Rinehart, J., Bobadilla, N.A., Vázquez, N., San Cristobal, P., Mount, D.B., Lifton, R.P., Hebert, S.C., Gamba, G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway. Veríssimo, F., Silva, E., Morris, J.D., Pepperkok, R., Jordan, P. Oncogene (2006) [Pubmed]
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