2. Academic Validation
  3. Human hypertension caused by mutations in WNK kinases

Human hypertension caused by mutations in WNK kinases

  • Science. 2001 Aug 10;293(5532):1107-12. doi: 10.1126/science.1062844.
F H Wilson 1,  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

Affiliation

  • 1 Howard Hughes Medical Institute; Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06510 USA.
PMID: 11498583 DOI: 10.1126/science.1062844
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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