SLC12A3

This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene.

Full Name

Solute Carrier Family 12 Member 3

Function

Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145).
Receptor for the pro-inflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).

Biological Process

Biological Process cell volume homeostasisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cellular response to inorganic substanceIEA:Ensembl
Biological Process chloride ion homeostasisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process chloride transmembrane transportManual Assertion Based On ExperimentIBA:GO_Central
Biological Process ion transportTAS:Reactome
Biological Process potassium ion homeostasisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process potassium ion import across plasma membraneManual Assertion Based On ExperimentIBA:GO_Central
Biological Process protein phosphorylationIEA:Ensembl
Biological Process response to aldosteroneIEA:Ensembl
Biological Process response to dietary excessIEA:Ensembl
Biological Process signal transductionIEA:Ensembl
Biological Process sodium ion homeostasisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process sodium ion transmembrane transportISS:BHF-UCL
Biological Process sodium ion transportISS:UniProtKB

Cellular Location

Cell membrane
Apical cell membrane

Topology

Cytoplasmic: 1-135
Helical: 136-156
Extracellular: 159-179
Helical: 180-218
Cytoplasmic: 219-239
Helical: 262-282
Extracellular: 283-286
Helical: 287-307
Cytoplasmic: 340-360
Helical: 361-377
Extracellular: 378-398
Helical: 453-473
Cytoplasmic: 474-511
Helical: 512-532
Extracellular: 535-555
Helical: 556-577
Cytoplasmic: 578-598
Helical: 661-681
Extracellular: 682-1021