Publication Date:
2001-08-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, F H -- Disse-Nicodeme, S -- Choate, K A -- Ishikawa, K -- Nelson-Williams, C -- Desitter, I -- Gunel, M -- Milford, D V -- Lipkin, G W -- Achard, J M -- Feely, M P -- Dussol, B -- Berland, Y -- Unwin, R J -- Mayan, H -- Simon, D B -- Farfel, Z -- Jeunemaitre, X -- Lifton, R P -- New York, N.Y. -- Science. 2001 Aug 10;293(5532):1107-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute; Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06510 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11498583" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Base Sequence
;
Chromosome Mapping
;
Chromosomes, Human, Pair 12/genetics
;
Chromosomes, Human, Pair 17/genetics
;
Cytoplasm/enzymology
;
Female
;
Gene Expression Regulation, Enzymologic
;
Genetic Linkage
;
Humans
;
Hypertension/enzymology/*genetics/physiopathology
;
Intercellular Junctions/enzymology
;
Intracellular Signaling Peptides and Proteins
;
Introns
;
Kidney Tubules, Collecting/enzymology/ultrastructure
;
Kidney Tubules, Distal/enzymology/ultrastructure
;
Male
;
Membrane Proteins/metabolism
;
Microscopy, Fluorescence
;
Molecular Sequence Data
;
*Mutation
;
Mutation, Missense
;
Pedigree
;
Phosphoproteins/metabolism
;
Protein-Serine-Threonine Kinases/chemistry/*genetics/metabolism
;
Pseudohypoaldosteronism/enzymology/*genetics/physiopathology
;
Sequence Deletion
;
Signal Transduction
;
Zonula Occludens-1 Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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