Gene: SLC12A3

Alternate names for this Gene: NCC|NCCT|TSC

Gene Summary: 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.

Gene is located in Chromosome: 16

Location in Chromosome : 16q13

Description of this Gene: solute carrier family 12 member 3

Type of Gene: protein-coding

rs121909379 in SLC12A3 gene and Gitelman Syndrome PMID 16429844 2006 A novel mutation of the thiazide-sensitive sodium chloride cotransporter gene in a Japanese family with Gitelman syndrome.

PMID 17873326 2007 Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome.

PMID 8528245 1996 Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.

PMID 8954067 1996 Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome.

PMID 17654016 2007 Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes.

PMID 9734597 1998 Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain.

PMID 21343949 2011 Clinical utility gene card for: Gitelman syndrome.

PMID 26099046 2015 Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter.

PMID 22009145 2012 Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome.

PMID 10988270 2000 Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension.

PMID 11168953 2001 Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life.

PMID 10616841 2000 Novel mutations in thiazide-sensitive Na-Cl cotransporter gene of patients with Gitelman's syndrome.

PMID 11940055 2002 Severe hypomagnesaemia-induced hypocalcaemia in a patient with Gitelman's syndrome.

PMID 15069170 2004 Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

PMID 26633545 2016 Molecular diagnostic experience of whole-exome sequencing in adult patients.

PMID 15687331 2005 Phenotype and genotype analysis in Chinese patients with Gitelman's syndrome.

PMID 8900229 1996 Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome.

PMID 12008755 2002 Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two sporadic Japanese patients with Gitelman syndrome.

PMID 12112667 2002 Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.

PMID 8954067 1996 In conclusion, the L623P mutation in the thiazide-sensitive Na-Cl cotransporter gene is suggested to impair the transporter activity, and to underlie this familial Gitelman's syndrome; Gitelman's syndrome observed in this kindred has been inherited in an autosomal recessive fashion.

PMID 12039972 2002 Functional expression of mutations in the human NaCl cotransporter: evidence for impaired routing mechanisms in Gitelman's syndrome.

PMID 23328711 2013 Unexpected clinical sequelae of Gitelman syndrome: hypertension in adulthood is common and females have higher potassium requirements.

PMID 21415153 2011 Spectrum of mutations in Gitelman syndrome.

PMID 26921350 2016 A Rare Case of Hypokalemia and Hypomagnesemia.

PMID 21753071 2011 Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome.

PMID 22169961 2012 Gitelman's syndrome: a pathophysiological and clinical update.

PMID 15976513 2005 Outcome of pregnancy in a patient with Gitelman syndrome: a case report.

PMID 28947054 2017 Potential Role of Genomic Sequencing in the Early Diagnosis of Treatable Genetic Conditions.

PMID 18391953 2008 Rare independent mutations in renal salt handling genes contribute to blood pressure variation.

PMID 21256383 2011 Family paralysis.

PMID 10616841 2000 Although further in vitro study is required to prove that the mutations are responsible for GS, it is possible that Thr180Lys and Arg642Cys mutations might be common mutations in Japanese GS.

PMID 11532083 2001 Abnormalities of Gq-mediated cell signaling in Bartter and Gitelman syndromes.

PMID 22990302 2013 Renal phosphate handling in Gitelman syndrome--the results of a case-control study.

PMID 19420906 2009 Clinical and analytical findings in Gitelman's syndrome associated with homozygosity for the c.1925 G>A SLC12A3 mutation.

PMID 17329572 2007 Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome.

PMID 25140267 2014 Gitelman Syndrome in a School Boy Who Presented with Generalized Convulsion and Had a R642H/R642W Mutation in the SLC12A3 Gene.

PMID 17699451 2007 A thiazide test for the diagnosis of renal tubular hypokalemic disorders.

PMID 23698802 2013 SIRT1, heme oxygenase-1 and NO-mediated vasodilation in a human model of endogenous angiotensin II type 1 receptor antagonism: implications for hypertension.

PMID 21757836 2011 A case of Gitelman syndrome associated with idiopathic intracranial hypertension.

PMID 16471174 2005 While the T180K variation was just a polymorphism, the L849H mutation was confirmed to be a loss-of-function mutation and appears to be responsible for the Gitelman's syndrome.

PMID 15198479 2004 Although the blood pressure levels of subjects heterozygous for the T180K, A569V, or L849H genotype were not significantly different from those of wild-type subjects, urine pH in subjects with GS mutations was significantly higher than that in subjects without mutations.

PMID 21628937 2011 Inheritance of an autosomal recessive disorder, Gitelman's syndrome, across two generations in one family.

PMID 22802996 2012 Concurrence of thyrotoxicosis and Gitelman's syndrome-associated hypokalemia-induced periodic paralysis.

PMID 23756661 2013 SLC26A3 gene analysis in patients with Bartter and Gitelman syndromes and the clinical characteristics of patients with unidentified mutations.

PMID 27173320 2016 Clinical and genetic analyses of Chinese patients with Gitelman syndrome.

PMID 12911530 2003 Analysis of renal tubular electrolyte transporter genes in seven patients with hypokalemic metabolic alkalosis.

PMID 26041598 2016 Graves' disease and Gitelman syndrome.

PMID 10616841 2000 Although further in vitro study is required to prove that the mutations are responsible for GS, it is possible that Thr180Lys and Arg642Cys mutations might be common mutations in Japanese GS.

PMID 27454426 2016 T60M and D486N were most frequent and appear to be important candidate alleles in Chinese patients with GS.

PMID 18287808 2008 Thr60Met may be the most common mutation in Chinese patients with GS.

PMID 19451210 2009 Four mutations (p.T60M, p.T304M, p.T465P, and p.N611T) harbored by the two patients with both PA and GS were revealed to be loss-of-function variants.

PMID 27453715 2016 He had a homozygous mutation in the 179(th) nucleotide of Exon 1 on the SLC12A3 gene (p.Thr60Met) and his parents and sisters were diagnosed as carrier state of Gitelman's syndrome (GS).

PMID 19207868 2009 Identification of five novel variants in the thiazide-sensitive NaCl co-transporter gene in Chinese patients with Gitelman syndrome.

PMID 24776766 2014 Clinical severity of Gitelman syndrome determined by serum magnesium.

PMID 23833262 2013 A T60M mutation in the thiazide-sensitive sodium chloride cotransporter (NCC) is common in patients with Gitelman's syndrome (GS).

PMID 27582097 2016 Functionomics of NCC mutations in Gitelman syndrome using a novel mammalian cell-based activity assay.

PMID 27872838 2016 New SLC12A3 disease causative mutation of Gitelman's syndrome.

PMID 22241817 2012 Localization of tubular adaptation to renal sodium loss in Gitelman syndrome.

PMID 26121437 2015 NORMOMAGNESEMIC GITELMAN SYNDROME PATIENTS EXHIBIT A STRONGER REACTION TO THIAZIDE THAN HYPOMAGNESEMIC PATIENTS.

PMID 15824853 2005 Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice.

PMID 22934535 2013 Novel missense mutations of WNK1 in patients with hypokalemic salt-losing tubulopathies.

PMID 8812482 1996 Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3).

PMID 17159356 2006 Genetic analysis of Gitelman syndrome patients from the Czech Republic and Slovakia--three novel mutations found.

PMID 23475471 2013 It is never too late for a genetic disease: a case of a 79-year-old man with persistent hypokalemia.

PMID 24790334 2006 Two Japanese patients with gitelman syndrome.

PMID 25112827 2014 Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation of a Gitelman syndrome.

PMID 20675610 2011 The mutation c.1196_1202dup7bp (p.Ser402X) in the SLC12A3 gene clusters in Italian Gitelman syndrome patients and reflects the presence of a common ancestor.

PMID 21051746 2011 Recurrent deep intronic mutations in the SLC12A3 gene responsible for Gitelman's syndrome.

rs1138429 in SLC12A3 gene and High density lipoprotein measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

rs1138429 in SLC12A3 gene and Serum HDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.