Solute carrier family 12 member 3 (NCC) (NCC)

The Solute carrier family 12 member 3, commonly known as the Sodium-chloride symporter (NCC), is a protein primarily expressed in the apical membrane of the distal convoluted tubule (DCT) in the kidney (UniProt P55017). Its primary biological function is the electroneutral reabsorption of sodium and chloride ions from the tubular fluid back into the blood, accounting for approximately 5-10% of filtered sodium (StatPearls, Thiazide Diuretics). By regulating salt reabsorption, NCC plays a critical role in maintaining blood pressure and extracellular fluid volume (PubMed, PMID: 25613444). Mutations in the SLC12A3 gene that cause a loss of function lead to Gitelman syndrome, a salt-wasting tubulopathy characterized by hypokalemia and metabolic alkalosis (NIH, Genetic and Rare Diseases Information Center). Conversely, overactivity of NCC is associated with hypertension. NCC is the primary pharmacological target for thiazide and thiazide-like diuretics, which are widely used as first-line treatments for hypertension and edema (PubChem, CID: 3639). These drugs bind to the chloride-binding site of the transporter, inhibiting its activity and promoting the excretion of salt and water.

Other names

Thiazide-sensitive sodium-chloride cotransporterTSCSLC12A3Sodium-chloride cotransporter

Thiazide diuretics inhibit the NCC by competing for the chloride binding site on the transporter, thereby reducing the reabsorption of sodium and chloride in the distal convoluted tubule (StatPearls, Thiazide Diuretics).