Human hypertension caused by mutations in WNK kinases

Research output: Contribution to journalArticle

Authors

  • FH Wilson
  • S Disse-Nicodeme
  • KA Choate
  • K Ishikawa
  • C Nelson-Williams
  • And 14 others
  • I Desitter
  • M Gunel
  • David Milford
  • Graham Lipkin
  • JM Achard
  • MP Feely
  • B Dussol
  • Y Berland
  • RJ Unwin
  • H Mavan
  • DB Simon
  • Z Farfel
  • X Jeunemaitre
  • RP Lifton

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)1107-1112
Number of pages6
JournalScience
Volume293
Publication statusPublished - 10 Aug 2001