Solute carrier family 12 member 3 (Thiazide-sensitive sodium-chloride cotransporter) (NCC)

SLC12A3, commonly referred to as the thiazide-sensitive sodium-chloride cotransporter (NCC), is a transmembrane protein located in the apical membrane of the distal convoluted tubule (DCT) of the kidney (UniProt P55017). Note that while the prompt associates SLC12A3 with the Na+/K+/2Cl- cotransporter, SLC12A3 specifically mediates the electroneutral reabsorption of sodium and chloride ions (Na+/Cl-), whereas Na+/K+/2Cl- transport is performed by SLC12A1 and SLC12A2 (Gamba, 2005, Physiological Reviews). Its primary biological function is the reabsorption of sodium and chloride from the pro-urine, which is essential for maintaining systemic blood pressure and fluid balance (Subramanya & Ellison, 2014, CJASN). Loss-of-function mutations in the SLC12A3 gene cause Gitelman syndrome, a rare autosomal recessive disorder characterized by low blood pressure, hypokalemia, and hypomagnesemia (Knoers & Levtchenko, 2008, Orphanet Journal of Rare Diseases). SLC12A3 is the molecular target for thiazide and thiazide-like diuretics, which are among the most frequently prescribed medications for hypertension and congestive heart failure (StatPearls, Thiazide Diuretics). These drugs bind to the chloride-binding site of the transporter, inhibiting ion reabsorption and promoting diuresis.

Other names

SLC12A3NCCNCCTTSCThiazide-sensitive sodium-chloride cotransporter

Inhibition of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule of the kidney, leading to increased excretion of sodium, chloride, and water.