Solute carrier family 12 member 3 (Sodium-chloride symporter) (NCC)

The Solute carrier family 12 member 3, commonly known as the sodium-chloride symporter (NCC), is a transmembrane protein located primarily in the apical membrane of the distal convoluted tubule (DCT) in the kidney. Its primary biological function is the electroneutral reabsorption of sodium and chloride ions from the tubular fluid back into the renal epithelial cells, accounting for approximately 5-10% of filtered sodium reabsorption (UniProt P55017; NIH/StatPearls). By regulating the amount of salt returned to the bloodstream, NCC plays a critical role in maintaining long-term blood pressure and extracellular fluid volume. Mutations in the SLC12A3 gene that cause a loss of function lead to Gitelman syndrome, characterized by low blood pressure and electrolyte imbalances, while overactivity is associated with hypertension (PubMed PMID: 25568244). NCC is the primary pharmacological target for thiazide and thiazide-like diuretics, which are first-line treatments for essential hypertension and edema. These drugs bind to the chloride-binding site of the transporter, inhibiting its activity and promoting the excretion of salt and water (PubChem; NIH/StatPearls).

Other names

Thiazide-sensitive sodium-chloride cotransporterTSCSLC12A3Na-Cl cotransporterSodium-chloride symporter

Inhibition of the sodium-chloride symporter in the distal convoluted tubule, which prevents the reabsorption of sodium and chloride ions, leading to increased natriuresis and diuresis.