SLC12A3

Interaction between the cytoplasmic N-terminal and C-terminal domains (NTD and CTD, respectively) is essential for SLC12A3/NCC transporter activity (PubMed:36792826). Phosphorylation by OXSR1/OSR1 and STK39/SPAK may activate SLC12A3/NCC by facilitating this interaction (PubMed:36792826).

Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).

Gitelman syndrome

GTLMNS

An autosomal recessive disorder characterized by hypokalemic alkalosis in combination with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. Patients are often asymptomatic or present transient periods of muscular weakness and tetany, usually accompanied by abdominal pain, vomiting and fever. The phenotype is highly heterogeneous in terms of age at onset and severity. Cardinal features such as hypocalciuria and hypomagnesemia might also change during the life cycle of a given patient. It has overlapping features with Bartter syndrome.

None

The disease is caused by variants affecting the gene represented in this entry.

Ubiquitinated; ubiquitination is essential for regulation of endocytosis. The BCR(KLHL3) complex was initially identified as a candidate ubiquitin ligase for SLC12A3 (PubMed:22406640). However, it was later shown that it is not the case.

Phosphorylated at Thr-46, Thr-55, Thr-60 and Ser-91 by OXSR1/OSR1 and STK39/SPAK downstream of WNK4, promoting its activity (PubMed:18270262). Phosphorylated in response to IL18 (By similarity).

Belongs to the SLC12A transporter family.

Predominantly expressed in the kidney (at protein level) (PubMed:29993276, PubMed:8812482). Localizes to the distal convoluted tubules (at protein level) (PubMed:29993276). Not detected in normal aorta, but abundantly expressed in fatty streaks and advanced atherosclerotic lesions (at protein level) (PubMed:26099046).

• Cell membrane
• Multi-pass membrane protein
• Apical cell membrane
• Multi-pass membrane protein

NCC, TSC, SLC12A3, Solute carrier family 12 member 3, Na-Cl cotransporter, Na-Cl symporter, Thiazide-sensitive sodium-chloride cotransporter

• entrezGene:6559
• omim:600968
• swissprot:P55017

Proteins

Immunology & Infectious Disease

113139Da