Defective SLC12A3 does not cotransport Cl-, Na+ from extracellular region to cytosol

Stable Identifier
R-HSA-5623705
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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The SLC12A3 gene encodes for the Thiazide-sensitive sodium-chloride cotransporter (TSC). TSC mediates sodium and chloride removal from the distal convoluted tubule of the kidney. Defects in SLC12A3 are the cause of Gitelman syndrome (GS aka familial hypokalemic hypomagnesemia; MIM:263800). GS is an autosomal recessive disorder characterised by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. Patients can present with periods of muscular weakness and tetany, usually accompanied by abdominal pain, vomiting and fever. GS has overlapping features with Bartter syndrome (caused by defects in SLC12A1). Mutations in SLC12A3 that can cause GS include L850P, L272P, G741R, T392I and E121D (Simon et al. 1996, Glaudemans et al. 2012). The most common mutation in Asian GS patients is T60M (Yang et al. 2013).

Literature References
PubMed ID Title Journal Year
22009145 Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome

Glaudemans, B, Yntema, HG, San-Cristobal, P, Schoots, J, Pfundt, R, Kamsteeg, EJ, Bindels, RJ, Knoers, NV, Hoenderop, JG, Hoefsloot, LH

Eur. J. Hum. Genet. 2012
8528245 Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter

Simon, DB, Nelson-Williams, C, Bia, MJ, Ellison, D, Karet, FE, Molina, AM, Vaara, I, Iwata, F, Cushner, HM, Koolen, M, Gainza, FJ, Gitleman, HJ, Lifton, RP

Nat Genet 1996
23833262 Phosphorylation regulates NCC stability and transporter activity in vivo

Yang, SS, Fang, YW, Tseng, MH, Chu, PY, Yu, IS, Wu, HC, Lin, SW, Chau, T, Uchida, S, Sasaki, S, Lin, YF, Sytwu, HK, Lin, SH

J. Am. Soc. Nephrol. 2013
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
sodium:chloride symporter activity of SLC12A3 mutants [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
Gitelman syndrome 0050450 HYPOMAGNESEMIA-HYPOKALEMIA, PRIMARY RENOTUBULAR, WITH HYPOCALCIURIA
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