Human hypertension caused by mutations in WNK kinases - PubMed (original) (raw)

. 2001 Aug 10;293(5532):1107-12.

doi: 10.1126/science.1062844.

S Disse-Nicodème, K A Choate, K Ishikawa, C Nelson-Williams, I Desitter, M Gunel, D V Milford, G W Lipkin, J M Achard, M P Feely, B Dussol, Y Berland, R J Unwin, H Mayan, D B Simon, Z Farfel, X Jeunemaitre, R P Lifton

Affiliations

Human hypertension caused by mutations in WNK kinases

F H Wilson et al. Science. 2001.

Abstract

Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.

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