'''Serine/threonine-protein kinase WNK4''' also known as '''WNK lysine deficient protein kinase 4''' or '''WNK4''', is an [[enzyme]] that in humans is encoded by the ''WNK4'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: WNK4 WNK lysine deficient protein kinase 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=65266| accessdate = }}</ref>
'''Serine/threonine-protein kinase WNK4''' also known as '''WNK lysine deficient protein kinase 4''' or '''WNK4''', is an [[enzyme]] that in humans is encoded by the ''WNK4'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: WNK4 WNK lysine deficient protein kinase 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=65266| accessdate = }}</ref>. Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.
Serine/threonine-protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4gene.[1]. Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.
The WNK4 gene encodes a serine-threonine kinase expressed in distal nephron.[1] Its primary role in renal physiology is as a molecular switch between the angiotensin II–aldosterone mediated volume retention and the aldosterone mediated potassium wasting. This is achieved by regulating the sodium-chloride symporter (NCC), that is uniquely expressed in the distal nephron and is sensitive to thiazide type diuretics.[2]
Under basal conditions (low circulating Ang II and low Aldosterone), WNK4 will inhibit NCC function. It has been proposed that in the event of hyperkalemia and an increased secretion of aldosterone (which will upregulate both ENac and ROMK), this inhibition of NCC, will allow an increase in the arrival of sodium to the distal nephron (rich in ENaC and ROMK) which will allow the exchange of sodium for potassium ions, thereby reducing plasma potassium levels, without increasing sodium chloride retention (which is always accompanied by volume expansion). Furthermore, it has been proposed that in the presence of AngII the WNK4 mediated NCC inhibition will be suppressed thereby increasing sodium-chloride reabsorption in the distal convoluted tubule. This along with the concomitant increase in passive water reabsortion due to the increased salt load in the distal convluted tubule cells will ultimately increase circulating volume.[3]
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