Solute carrier family 12 member 3

UniProt P55017 Organism Homo sapiens Gene NCC, SLC12A3, TSC

Also known as: NCC, SLC12A3, TSC

Function

Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules. 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).

Classification

Family (Pfam): PF00324 AA_permease, PF08403 AA_permease_N, PF03522 SLC12
InterPro: AA-permease/SLC12A_dom, AA_permease_N, SLC12_C, SLC12A3, SLC12A_fam
Functional cluster: Membrane Transporters & GPCRs

Experimental structures · PDB · 9

7Y6I EM 2.85A
7YG0 EM 3.75A
7YG1 EM 3.77A
8FHN EM 3.00A
8FHO EM 2.95A
8FHP EM 3.04A
8FHQ EM 2.81A
8FHR EM 2.90A
8FHT EM 3.02A

A predicted model is available from AlphaFold.

Gene Ontology · 19

Disease associations

Gitelman syndrome MONDO:0009904

Drugs targeting this protein · 14

TRICHLORMETHIAZIDE inhibitor
CHLORTHALIDONE inhibitor
CHLOROTHIAZIDE SODIUM inhibitor
BENZTHIAZIDE inhibitor
QUINETHAZONE inhibitor
METHYCLOTHIAZIDE inhibitor
POLYTHIAZIDE inhibitor
BENDROFLUMETHIAZIDE inhibitor
HYDROFLUMETHIAZIDE inhibitor
INDAPAMIDE inhibitor
HYDROCHLOROTHIAZIDE inhibitor
CYCLOTHIAZIDE inhibitor
CHLOROTHIAZIDE inhibitor
METOLAZONE inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Solute carrier family 12 member 3 3 shared papers
Interleukin-18 receptor 1 1 shared papers
Kelch-like protein 3 1 shared papers
STE20/SPS1-related proline-alanine-rich protein kinase 1 shared papers
Solute carrier family 12 member 1 2 shared papers
Kelch-like protein 3 1 shared papers
Serine/threonine-protein kinase OSR1 1 shared papers
V-type proton ATPase subunit B, kidney isoform 1 shared papers
V-type proton ATPase subunit G 1 1 shared papers
Solute carrier family 12 member 7 1 shared papers
Solute carrier family 12 member 2 1 shared papers
Solute carrier family 12 member 5 1 shared papers

Literature · 35 cited papers

Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter. Nature · 2023
Gitelman syndrome - A new mutation in the SLC12A3 gene. Nefrologia · 2022
R158Q and G212S, novel pathogenic compound heterozygous variants in SLC12A3 of Gitelman syndrome. Front. Med. · 2022
Cryo-EM structure of the human sodium-chloride cotransporter NCC. Sci. Adv. · 2022
A novel mutation of SLC12A3 gene causing Gitelman syndrome. SAGE Open Med. Case Rep. · 2022
Novel mutations of the SLC12A3 gene in patients with Gitelman syndrome. Scand. J. Clin. Lab. Invest. · 2021
Three Novel Homozygous Mutations of the SLC12A3 Gene in a Gitelman Syndrome Patient. Int. J. Gen. Med. · 2021
Novel heterozygous mutation of SLC12A3 gene in Gitelman syndrome. QJM · 2021
Novel SLC12A3 mutation in Gitelman syndrome. BMJ Case Rep. · 2021
H+-ATPase B1 subunit localizes to thick ascending limb and distal convoluted tubule of rodent and human kidney. Am. J. Physiol. · 2018
Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter. Nat. Med. · 2015
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
… and 23 more in the literature graph

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