Thiazide-sensitive Na-K-Cl co-transporter (IPR002948)

Short name: SLC12A3

Overlapping homologous superfamilies


Family relationships


Solute carrier family 12 member 3 (Slc12a3) is also known as Tsc (thiazide-sensitive Na-Cl co-transporter). Tsc is a large integral membrane protein (~1000 amino acids) that mediates the coupled transport of Na+ and Cl- in an electrically silent manner. In the mammalian kidney, it is the dominant mechanism mediating Cl- absorption in the early distal tubule, and here 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 winter flounder (Pseudopleuronectes americanus), from where the gene encoding it was initially cloned [PMID: 8464884].

Hydrophobicity analysis predicts the Na-Cl co-transporter to have 12 transmembrane (TM) domains and comparisons with other cloned ion co-transporters reveals that a superfamily of electroneutral cation-chloride co-transporters exists, which includes the K-Cl co-transporters (IPR000076) and the Na-K-Cl co-transporters (IPR002443). All share a similar predicted membrane topology in a central hydrophobic domain, together with hydrophilic N- and C-termini that are likely cytoplasmic [PMID: 9639584].

Mutations in the thiazide-sensitive Na-Cl co-transporter have been found that give rise to Gitelman's variant of Bartter's syndrome, an inherited kidney disease characterised by hypokalaemic alkalosis [PMID: 8528245].

GO terms

Biological Process

GO:0006811 ion transport

Molecular Function

GO:0005215 transporter activity

Cellular Component

GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.