KELCH3

The renal thiazide-sensitive NaCl cotransporter (NCC) is the major salt transport pathway in the distal convoluted tubule of the mammalian nephron. NCC activity is critical for modulation of arterial blood pressure and serum potassium levels. Reduced activity of NCC in genetic diseases results in arterial hypotension and hypokalemia, while increased activity results in genetic diseases featuring hypertension and hyperkalemia. Several hormones and physiological conditions modulate NCC activity through a final intracellular complex pathway involving kinases and ubiquitin ligases...

Gordon Syndrome (GS) is a rare familial hypertension syndrome with a characteristic hyperkalaemia which distinguishes it from other syndromic forms of hypertension that typically cause hypokalaemia. Patients with GS respond to aggressive salt-restriction or relatively small doses of thiazide diuretics, which suggests that activation of the thiazide-sensitive Na/Cl cotransporter (NCC) in the distal nephron is to blame. However, the mechanism has proved to be complex. In 2001, mutations in genes encoding two serine/threonine kinases, WNK1 and WNK4, were identified as causing GS...