SLC12A1

This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]

Full Name

Solute Carrier Family 12 Member 1

Function

Renal sodium, potassium and chloride ion cotransporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation. Electrically silent transporter system.

Biological Process

Biological Process cell volume homeostasisManual Assertion Based On ExperimentIBA:GO_Central
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 transmembrane transportISS:BHF-UCL
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 sodium ion homeostasisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process sodium ion transmembrane transportManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Apical cell membrane

Involvement in disease

Bartter syndrome 1, antenatal (BARTS1):
A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS1 is a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia.

Topology

Cytoplasmic: 1-177
Helical: 178-198
Extracellular: 202-222
Helical: 223-259
Cytoplasmic: 260-280
Helical: 303-323
Extracellular: 324-327
Helical: 328-348
Cytoplasmic: 380-400
Helical: 401-417
Extracellular: 418-438
Helical: 485-505
Cytoplasmic: 506-550
Helical: 551-571
Extracellular: 572-592
Helical: 593-609
Cytoplasmic: 610-630
Helical: 793-813
Extracellular: 814-1099