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Tclin Solute carrier family 12 member 3

Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145). Receptor for the proinflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).

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. [provided by RefSeq, Jul 2008]

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Property Summary

NCBI Gene PubMed Count 102
PubMed Score 543.61
PubTator Score 285.46

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (6)

Disease Target Count P-value
psoriasis 6685 6.4e-23
ovarian cancer 8491 1.5e-08
malignant mesothelioma 3163 1.9e-07
osteosarcoma 7933 3.3e-05
cutaneous lupus erythematosus 1056 4.6e-03
Disease Target Count Z-score Confidence
Cardiovascular system disease 194 0.0 2.0
Disease Target Count
Gitelman syndrome 7

Expression

  Differential Expression (5)

Disease log2 FC p
malignant mesothelioma 2.900 1.9e-07
cutaneous lupus erythematosus 1.700 4.6e-03
osteosarcoma -1.034 3.3e-05
ovarian cancer 1.200 1.5e-08
psoriasis 1.900 6.4e-23

Synonym

Accession P55017 A8MSJ2 C9JNN9
Symbols NCC
TSC
NCCT

Gene

SLC12A3

  Ortholog (2)

Species Source Disease
Chimp OMA EggNOG
Mouse OMA EggNOG Inparanoid Chondrocalcinosis [JensenLab Text Mining]
Gitelman syndrome [Monarch]

 UniProt Keyword (17)

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 GO Function (2)

 GO Component (6)

 GO Process (4)

 Compartment GO Term (25)

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 OMIM Phenotype (1)

 MGI Phenotype (3)

 HCA RNA Cell Line (43)

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Pathway (34)

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Drug (13)

Structure of trichlormethiazide

trichlormethiazide
A2 7.00

Structure of polythiazide

polythiazide
A2 9.09

Structure of indapamide

indapamide
A2 7.54

Structure of hydroflumethiazide

hydroflumethiazide
A2 7.37

Structure of hydrochlorothiazide

hydrochlorothiazide
A2 7.01

Structure of chlorothiazide

chlorothiazide
A2 5.43

Structure of benzthiazide

benzthiazide
A2 8.17

Structure of bendroflumethiazide

bendroflumethiazide
A2 8.30

Structure of quinethazone

quinethazone

Structure of chlortalidone

chlortalidone

Structure of methylclothiazide

methylclothiazide

Structure of metolazone

metolazone

Structure of cyclothiazide

cyclothiazide

Gene RIF (92)

PMID Text
26770037 Compared with patients with 1 mutant SLC12A3 allele, patients with 2 mutant SLC12A3 alleles had more severe hypomagnesemia, but did not have more severe hypokalemia.
26561651 Suggest NCC1/2 is a fully functional thiazide-sensitive NaCl-transporting protein in the kidney.
26345939 the results of this study support that the SLC12A3 gene is a susceptibility gene for hypertension in the Mongolian population.
25931204 In urinary exosomes, NCC and prostasin had a diurnal pattern parallel to ADH and aquaporin 2, confirming that, in healthy subjects, both prostasin and NCC relate to water balance.
25841442 association between thiazide-sensitive Na(+)-Cl(-) cotransporter mutants and human hypertension as well as Gitelman's syndrome (review).
25422309 Low SLC12A3 urine levels were associated with Gitelman syndrome.
25401745 SLC12A3 Arg913Gln polymorphism was associated with Type 2 diabetes and diabetic nephropathy in the Malaysian cohort. The meta-analysis confirmed the protective effects of SLC12A3 913Gln allele in diabetic nephropathy.
25273610 Data from two families in China suggest two homozygous mutations in SLC12A3 (Arg928Cys or Ser710X) can be associated with Gitelman syndrome; members of two families exhibit additional mutations and heterogenicity of clinical phenotype. [CASE STUDY]
25165177 Mutation in the SLC12A3 gene is associated with gitelman syndrome and glomerular proteinuria.
25060058 Identification of candidate mutations in the SLC12A3 gene that may induce exon skipping.
24668812 a model where NCC is constitutively cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to both increase NCC activity and decrease NCC endocytosis, together increasing NaCl transport in the DCT.
24433479 the SLC12A3 34372 AA genotype is associated with a reduced risk of diabetes.
24430698 findings demonstrate a predominant role played by SLC12A3 gene rs5804 in determining hypertension risk among northeastern Han Chinese
24026181 Highly increased excretion of total urinary NCC and phosphorylated NCC is observed in type II pseudohypoaldosteronism patients.
23993962 These results suggest that WNK4 attenuates plasma membrane targeting of NCC proteins through regulation of syntaxin 13 SNARE complex formation with VAMP2 in recycling and sorting endosome.
23833262 Total urine NCC excretion is diminished in a cohort of Gitelman's syndrome patients with homozygous NCC mutations.
23482560 Hsp70 and Hsp90 comprise two functionally distinct ER quality control checkpoints that sequentially monitor NCC biogenesis.
23156397 Analysis of SNP databases of Japanese patuients with diabetic nephropathy revealed SLC12A3 as a gene related to the above-cited diabetic complication.
23079845 The TSC gene Arg904Gln polymorphism is not associated with essential hypertension risk.
22679066 Forty different SLC12A3 mutations were identified
22627394 The NCC mutation p.Thr60Met carriers in Han populations have markedly lower blood pressure and slightly higher fasting plasma glucose compared with normal controls.
22568564 Association with SNP rs999662 indicates a potential role for the region containing the solute carrier family 12 member 3 (SLC12A3) gene in transcranial Doppler vasospasm following sub-arachnoid hemorrhage.
22027832 NCC exhibits distinct ERAD requirements, which correlate with its transmembrane topology and distinguish it from other clients
22009145 The study shows the identification of 38 novel mutations in the SLC12A3 gene and provides insight into the mechanisms that regulate the thiazide-sensitive NaCl cotransporter.
21852580 Aldosterone modulates NCC protein expression via a pathway involving SGK1 and Nedd4-2.
21753071 In adult patients referred for renal hypokalaemia, we confirmed the presence of mutations of the SLC12A3 gene in 80% of cases
21644212 there was no significant association between the SLC12A3 R904Q variant and the ClC-Kb-T481S variant and essential hypertension in Mongolian and Han populations in Inner Mongolia
21644207 findings suggest that rs7204044 of TSC is a genetic factor for essential hypertension (EH) in Mongolian and Han populations and that rs13306673 is a genetic factor for EH in the Han population
21631963 seven different causative mutations in the SLC12A3 gene among patients suffering from bartter and Gitelman syndromes
21613606 The Wnk3 protein isoforms have a similar effect on SLC12 cotransporters. NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions.
21415153 Missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.
21196779 Data show that K1169E lost its inhibitory effect on NCC surface expression compared to wild-type WNK4 when expressed in HEK293 cells, while it did not change NCC total protein expression.
21164023 gamma-adducin may influence blood pressure homeostasis by modulating renal NaCl transport.
21161146 Mutation leads to a failure of the thiazide-sensitive sodium-2-chloride-cotransporter, the so called Gitelman syndrome, which presents similar to a chronic thiazide therapy
21051746 Deep intronic mutations in SLC12A3 causing defective transporter expression can be identified in Gitelman's syndrome.
20889219 Observational study of gene-disease association. (HuGE Navigator)
20675610 likely that the c.1196_1202dup7bp mutation in the SLC12A3 gene reflects the presence of a common ancestor in Gitelman syndrome an area covering the northern-central part of Italy and eastern France.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19875813 WNK4 promotes sodium chloride co-transporter targeting to the lysosome for degradation via a mechanism involving sortilin.
19779464 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19668106 analysis of how a deep intronic mutation in the SLC12A3 gene leads to Gitelman syndrome [case report]
19489442 Observational study of gene-disease association. (HuGE Navigator)
19451210 9 novel SLC12A3 gene variants, including seven missense mutations, one splice mutation, and one frameshift deletion, were found in 12 subjectsiwth Gitelman's syndrome and aldosteronism.
19420906 homozygosity for this mutation resulted in a significant loss of normal SLC12A3 transcript
19207868 13 variants, including five novel variants in the SLC12A3 gene in 13 patients with Gitelman syndrome.
19033254 Observational study of gene-disease association. (HuGE Navigator)
18580052 analysis of a novel SLC12A3 splicing mutation skipping of two exons and preliminary screening for alternative splice variants in human kidney [case report]
18496130 Observational study of gene-disease association. (HuGE Navigator)
18469313 sequencing of PVALB was performed in 132 cases of Gitelman's syndrome in whom only one or no (N = 79) mutant SLC12A3 allele was found
18391953 Members of the Framingham Heart Study were screened for variation in three genes-SLC12A3, SLC12A1 and KCNJ1 causing rare recessive diseases featuring large reductions in blood pressure.
18391953 Observational study of gene-disease association. (HuGE Navigator)
18362449 The causal gene of Gitelman's syndrome (SLC12A3) is not involved in determining blood pressure levels.
18362449 Observational study of gene-disease association. (HuGE Navigator)
18287808 Thr60Met may be the most common mutation in Chinese patients with GS. Possible specific genotype-phenotype correlations were difficult to identify.
18270262 The WNK1-SPAK/OSR1 signalling pathway plays a key role in controlling the phosphorylation and activity of NCC.
18263927 Genetic variation at the SLC12A3 locus is unlikely to explain the risk for advanced diabetic nephropathy among type 2 diabetic Caucasians.
18263927 Observational study of gene-disease association. (HuGE Navigator)
18067089 Observational study of gene-disease association. (HuGE Navigator)
17997379 roles of Thr418Ser polymorphism of the CLCNKB gene and Arg904Gln polymorphism in the TSC gene on essential hypertension need to be explored in other ethnic groups
17981812 Gitelmans syndrome heterozygotes are partially protected from hypertension through partial genetic loss of function of the NCCT.
17975670 Results report that WNK3, another member of the WNK kinase family expressed by distal tubule cells, interacts with WNK4 and WNK1 to regulate NCC in both human kidney cells and Xenopus oocytes.
17954289 No relation was found between sodium-chloride cotransporter expression and type of mutation in the SLC12A3 gene was found in patients with Gitelman syndrome.
17885550 substitution of arginine for cysteine at position 919 increases Na transport function and supports the hypothesis that mutations in renal tubular Na transporters contribute to the development of primary hypertension by increasing renal Na reabsorption
17873326 Two sporadic cases of Gitelman's syndrome and two novel genotypes of SLC12A3.
17654016 Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes.
17653210 Observational study and genome-wide association study of gene-disease association and gene-gene interaction. (HuGE Navigator)
17460608 Observational study of gene-environment interaction and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17329572 data suggest that the nature/position of SLC12A3 mutation, combined with male gender, is a determinant factor in the severity of Gitelman syndrome and provide new insights in the underlying pathogenic mechanisms of the disease
17159356 13 different causative mutations in a cohort of Gitelman syndrome patients
16887815 NCC is activated by a mechanism that involves amino-terminal domain phosphorylation
16688122 data suggest that WNK4 wild type significantly inhibits sodium chloride cotransporter (NCC) surface expression, not owing to an increase in clathrin-mediated endocytosis of NCC, but likely from enhanced degradation of NCC through a lysosomal pathway
16505253 Observational study of gene-disease association. (HuGE Navigator)
16221718 Patient with Gitelman syndrome is due to a mutation of the SLC123A gene.
15915338 Observational study of gene-disease association. (HuGE Navigator)
15915338 SLC12A3 +78A(+) genotype may have a protective effect against the development and/or progression of diabetic nephropathy in Japanese type 2 diabetic patients.
15824464 Observational study of gene-environment interaction and pharmacogenomic / toxicogenomic. (HuGE Navigator)
15480096 Observational study of gene-disease association. (HuGE Navigator)
15480096 G2736A polymorphism of the TSC gene is a genetic predisposing factor for essential hypertension in Japanese women.
15309683 Observational study of gene-disease association. (HuGE Navigator)
15102966 Human site directed mutagenesis is associated with Gitelman Syndrome in mice.
15069170 Observational study of gene-disease association. (HuGE Navigator)
14766743 the G264A polymorphism is associated with reduction in the substrate translocation rate of the cotransporter, due to a decrease in the intrinsic activity
14675033 novel point mutation within the SLC12A3 gene in our cohort of Gypsy families with Gitelman syndrome is highly suggestive of a founder effect.
14655226 7 different mutations of the NCCT gene were identified consisting of 3 missense, 1 splice site, and 3 silent mutations. Four of these mutations were novel.
14578305 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
14578305 Diabetic patients at >55,000 SNP loci indicated a gene encoding solute carrier family 12 member 3 (SLC12A3) to be a good candidate for the susceptibility to diabetic nephropathy
12686679 Novel thiazide-sensitive Na-Cl cotransporter mutation in a Chinese patient with Gitelman's syndrome presenting as hypokalaemic paralysis.
11893344 gene mutation associated with hypokalemic salt-losing tubulopathies.
11832422 Interaction with grp58 increases activity of the thiazide-sensitive Na-Cl cotransporter.
11564973 Observational study of gene-disease association. (HuGE Navigator)

AA Sequence 

MAELPTTETPGDATLCSGRFTISTLLSSDEPSPPAAYDSSHPSHLTHSSTFCMRTFGYNTIDVVPTYEHY      1 - 70
ANSTQPGEPRKVRPTLADLHSFLKQEGRHLHALAFDSRPSHEMTDGLVEGEAGTSSEKNPEEPVRFGWVK     71 - 140
GVMIRCMLNIWGVILYLRLPWITAQAGIVLTWIIILLSVTVTSITGLSISAISTNGKVKSGGTYFLISRS    141 - 210
LGPELGGSIGLIFAFANAVGVAMHTVGFAETVRDLLQEYGAPIVDPINDIRIIAVVSVTVLLAISLAGME    211 - 280
WESKAQVLFFLVIMVSFANYLVGTLIPPSEDKASKGFFSYRADIFVQNLVPDWRGPDGTFFGMFSIFFPS    281 - 350
ATGILAGANISGDLKDPAIAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGVLNDTVTPGWGACEGLA    351 - 420
CSYGWNFTECTQQHSCHYGLINYYQTMSMVSGFAPLITAGIFGATLSSALACLVSAAKVFQCLCEDQLYP    421 - 490
LIGFFGKGYGKNKEPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSYALINFSCFHASITNSPGWRP    491 - 560
SFQYYNKWAALFGAIISVVIMFLLTWWAALIAIGVVLFLLLYVIYKKPEVNWGSSVQAGSYNLALSYSVG    561 - 630
LNEVEDHIKNYRPQCLVLTGPPNFRPALVDFVGTFTRNLSLMICGHVLIGPHKQRMPELQLIANGHTKWL    631 - 700
NKRKIKAFYSDVIAEDLRRGVQILMQAAGLGRMKPNILVVGFKKNWQSAHPATVEDYIGILHDAFDFNYG    701 - 770
VCVMRMREGLNVSKMMQAHINPVFDPAEDGKEASARVDPKALVKEEQATTIFQSEQGKKTIDIYWLFDDG    771 - 840
GLTLLIPYLLGRKRRWSKCKIRVFVGGQINRMDQERKAIISLLSKFRLGFHEVHILPDINQNPRAEHTKR    841 - 910
FEDMIAPFRLNDGFKDEATVNEMRRDCPWKISDEEITKNRVKSLRQVRLNEIVLDYSRDAALIVITLPIG    911 - 980
RKGKCPSSLYMAWLETLSQDLRPPVILIRGNQENVLTFYCQ                                 981 - 1021
//

Text Mined References (116)

PMID Year Title
26770037 2016 Mutations in SLC12A3 and CLCNKB and Their Correlation with Clinical Phenotype in Patients with Gitelman and Gitelman-like Syndrome.
26561651 2016 Alternative splice variant of the thiazide-sensitive NaCl cotransporter: a novel player in renal salt handling.
26345939 2015 Association of variants in renal salt reabsorption-related gene SLC12A3 with essential hypertension in a Mongolian population.
26099046 2015 Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter.
25931204 2015 Circadian exosomal expression of renal thiazide-sensitive NaCl cotransporter (NCC) and prostasin in healthy individuals.
25841442 2015 Thiazide-sensitive Na+-Cl- cotransporter: genetic polymorphisms and human diseases.
25422309 2015 Urinary exosomes in the diagnosis of Gitelman and Bartter syndromes.
25401745 2014 Genetic and biological effects of sodium-chloride cotransporter (SLC12A3) in diabetic nephropathy.
25273610 2015 A pedigree analysis of two homozygous mutant Gitelman syndrome cases.
25165177 2014 Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction?
25060058 2015 Exonic mutations in the SLC12A3 gene cause exon skipping and premature termination in Gitelman syndrome.
24668812 2014 Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis.
24433479 2014 Variations in CCR5, but not HFE, ELMO1, or SLC12A3, are associated with susceptibility to kidney disease in north Indian individuals with type 2 diabetes.
24430698 2014 Tag polymorphisms of solute carrier family 12 member 3 gene modify the risk of hypertension in northeastern Han Chinese.
24026181 2013 Development of enzyme-linked immunosorbent assays for urinary thiazide-sensitive Na-Cl cotransporter measurement.
23993962 2013 WNK4 inhibits plasma membrane targeting of NCC through regulation of syntaxin13 SNARE formation.
23833262 2013 Phosphorylation regulates NCC stability and transporter activity in vivo.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23505323 2013 Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.
23482560 2013 Hsp70 and Hsp90 multichaperone complexes sequentially regulate thiazide-sensitive cotransporter endoplasmic reticulum-associated degradation and biogenesis.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23156397 2012 [Genetic study for diabetic microvascular complications--recent advances and future perspectives].
23079845 2012 Lack of an association between TSC gene Arg904Gln polymorphisms and essential hypertension risk based on a meta-analysis.
22679066 2012 Genotype, phenotype, and follow-up in Taiwanese patients with salt-losing tubulopathy associated with SLC12A3 mutation.
22627394 2012 High-frequency variant p.T60M in NaCl cotransporter and blood pressure variability in Han Chinese.
22568564 2013 Cerebral vasospasm after sub-arachnoid hemorrhage as a clinical predictor and phenotype for genetic association study.
22406640 2012 KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.
22027832 2011 The thiazide-sensitive NaCl cotransporter is targeted for chaperone-dependent endoplasmic reticulum-associated degradation.
22009145 2012 Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome.
21852580 2011 Nedd4-2 modulates renal Na+-Cl- cotransporter via the aldosterone-SGK1-Nedd4-2 pathway.
21753071 2011 Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome.
21644212 2011 Lack of association of variants of the renal salt reabsorption-related genes SLC12A3 and ClC-Kb and hypertension in Mongolian and Han populations in Inner Mongolia.
21644207 2011 Association of TSC gene variants and hypertension in Mongolian and Han populations.
21631963 2011 DNA analysis of renal electrolyte transporter genes among patients suffering from Bartter and Gitelman syndromes: summary of mutation screening.
21613606 2011 Similar effects of all WNK3 variants on SLC12 cotransporters.
21415153 2011 Spectrum of mutations in Gitelman syndrome.
21397062 2011 CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia.
21196779 2011 Identification of a novel WNK4 mutation in Chinese patients with pseudohypoaldosteronism type II.
21164023 2011 ?-Adducin stimulates the thiazide-sensitive NaCl cotransporter.
21161146 2011 [Salt appetite, cramps and palpitations in a 21-year old medical secretary].
21082674 2010 Comprehensive analysis of low-abundance proteins in human urinary exosomes using peptide ligand library technology, peptide OFFGEL fractionation and nanoHPLC-chip-MS/MS.
21051746 2011 Recurrent deep intronic mutations in the SLC12A3 gene responsible for Gitelman's syndrome.
20889219 2012 STK39 is an independent risk factor for male hypertension in Han Chinese.
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.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20031564 2009 Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: Genomewide analysis among 18 245 initially healthy women from the Women's Genome Health Study.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19875813 2010 WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway.
19779464 2009 Genetic factors are relevant and independent determinants of antihypertensive drug effects in a multiracial population.
19668106 2009 A deep intronic mutation in the SLC12A3 gene leads to Gitelman syndrome.
19489442 2009 [Mutational analysis of a thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in a Japanese population--the Iwaki Health Promotion Project].
19451210 2009 Coexistence of normotensive primary aldosteronism in two patients with Gitelman's syndrome and novel thiazide-sensitive Na-Cl cotransporter mutations.
19420906 2009 Clinical and analytical findings in Gitelman's syndrome associated with homozygosity for the c.1925 G>A SLC12A3 mutation.
19207868 2009 Identification of five novel variants in the thiazide-sensitive NaCl co-transporter gene in Chinese patients with Gitelman syndrome.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
19033254 2009 Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure.
18580052 2008 A novel SLC12A3 splicing mutation skipping of two exons and preliminary screening for alternative splice variants in human kidney.
18496130 2008 Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia.
18469313 2008 Evaluating PVALB as a candidate gene for SLC12A3-negative cases of Gitelman's syndrome.
18391953 2008 Rare independent mutations in renal salt handling genes contribute to blood pressure variation.
18362449 2008 Case-control study of the role of the Gitelman's syndrome gene in essential hypertension.
18287808 2008 Novel SLC12A3 mutations in Chinese patients with Gitelman's syndrome.
18270262 2008 Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1.
18263927 2008 Genetic variation at the SLC12A3 locus is unlikely to explain risk for advanced diabetic nephropathy in Caucasians with type 2 diabetes.
18067089 2007 [Association of thiazide-sensitive Na+-Cl* cotransporter gene polymorphisms with the risk of essential hypertension].
17997379 2008 Association study of variants in two ion-channel genes (TSC and CLCNKB) and hypertension in two ethnic groups in Northwest China.
17981812 2008 Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure.
17975670 2007 The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex.
17954289 2007 Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: preliminary data.
17885550 2007 Molecular variants of the thiazide-sensitive Na+-Cl- cotransporter in hypertensive families.
17873326 2007 Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome.
17654016 2007 Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes.
17653210 2007 Genetic variations associated with diabetic nephropathy and type II diabetes in a Japanese population.
17460608 2007 Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs.
17329572 2007 Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome.
17159356 2006 Genetic analysis of Gitelman syndrome patients from the Czech Republic and Slovakia--three novel mutations found.
16887815 2006 The Na+:Cl- cotransporter is activated and phosphorylated at the amino-terminal domain upon intracellular chloride depletion.
16688122 2006 WNK4 kinase regulates surface expression of the human sodium chloride cotransporter in mammalian cells.
16505253 2006 SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) polymorphisms are associated with end-stage renal disease in diabetic nephropathy.
16429844 2006 A novel mutation of the thiazide-sensitive sodium chloride cotransporter gene in a Japanese family with Gitelman syndrome.
16221718 2006 Gitelman syndrome: genetic and expression analysis of the thiazide-sensitive sodium-chloride transporter in blood cells.
15915338 2005 Polymorphism of the solute carrier family 12 (sodium/chloride transporters) member 3, SLC12A3, gene at exon 23 (+78G/A: Arg913Gln) is associated with elevation of urinary albumin excretion in Japanese patients with type 2 diabetes: a 10-year longitudinal study.
15824464 2004 The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics.
15687331 2005 Phenotype and genotype analysis in Chinese patients with Gitelman's syndrome.
15616553 2004 The sequence and analysis of duplication-rich human chromosome 16.
15480096 2004 G2736A polymorphism of thiazide-sensitive Na-Cl cotransporter gene predisposes to hypertension in young women.
15309683 2004 Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population.
15102966 2004 Effects of chemical chaperones on partially retarded NaCl cotransporter mutants associated with Gitelman's syndrome in a mouse cortical collecting duct cell line.
15069170 2004 Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.
14766743 2004 A single nucleotide polymorphism alters the activity of the renal Na+:Cl- cotransporter and reveals a role for transmembrane segment 4 in chloride and thiazide affinity.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14675033 2004 A new mutation (intron 9 +1 G>T) in the SLC12A3 gene is linked to Gitelman syndrome in Gypsies.
14655226 2003 Identification of novel mutations in Na-Cl cotransporter gene in a Korean patient with atypical Gitelman's syndrome.
14578305 2003 Association of solute carrier family 12 (sodium/chloride) member 3 with diabetic nephropathy, identified by genome-wide analyses of single nucleotide polymorphisms.
12686679 2003 Novel thiazide-sensitive Na-Cl cotransporter mutation in a Chinese patient with Gitelman's syndrome presenting as hypokalaemic paralysis.
12515852 2003 Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12112667 2002 Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.
12008755 2002 Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two sporadic Japanese patients with Gitelman syndrome.
11940055 2002 Severe hypomagnesaemia-induced hypocalcaemia in a patient with Gitelman's syndrome.
11832422 2002 Interaction with grp58 increases activity of the thiazide-sensitive Na-Cl cotransporter.
11564973 2001 Non-association of the thiazide-sensitive Na,Cl-cotransporter gene with polygenic hypertension in both rats and humans.
11168953 2001 Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life.
11076863 2000 DNA cloning using in vitro site-specific recombination.
10988270 2000 Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension.
10616841 2000 Novel mutations in thiazide-sensitive Na-Cl cotransporter gene of patients with Gitelman's syndrome.
9734597 1998 Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain.
9596079 1998 Peripheral blood mononuclear cells express mutated NCCT mRNA in Gitelman's syndrome: evidence for abnormal thiazide-sensitive NaCl cotransport.
8954067 1996 Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome.
8900229 1996 Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome.
8812482 1996 Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3).
8670281 1996 Identification of a cDNA encoding a thiazide-sensitive sodium-chloride cotransporter from the human and its mRNA expression in various tissues.
8528245 1996 Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.