Solute carrier family 12 member 3 (Slc12a3) is also known as Tsc (thiazide-sensitive Na-Cl co-transporter). Tsc is a large integral membraneprotein (~1000 amino acids) that mediates the coupled transport of Na+andCl-in an electrically silent manner. In the mammalian kidney, it is thedominant mechanism mediating Cl-absorption in the early distal tubule, andhere it is the target of the widely-used thiazide class of diuretic drugs.It is also known to be present in the urinary bladder of the winterflounder (Pseudopleuronectes americanus), from where the gene encoding it was initially cloned [].Hydrophobicity analysis predicts the Na-Cl co-transporter to have 12transmembrane (TM) domains and comparisons with other cloned ionco-transporters reveals that a superfamily of electroneutral cation-chlorideco-transporters exists, which includes the K-Cl co-transporters ()and the Na-K-Cl co-transporters (). All share a similar predictedmembrane topology in a central hydrophobic domain, together withhydrophilic N- and C-termini that are likely cytoplasmic [].Mutations in the thiazide-sensitive Na-Cl co-transporter have beenfound that give rise to Gitelman's variant of Bartter's syndrome,an inherited kidney disease characterised by hypokalaemic alkalosis [].
