Human hypertension caused by mutations in WNK kinases
FH Wilson, S Disse-Nicodeme, KA Choate, K Ishikawa… - Science, 2001 - science.org
FH Wilson, S Disse-Nicodeme, KA Choate, K Ishikawa, C Nelson-Williams, I Desitter…
Science, 2001•science.orgHypertension 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 …
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 …
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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