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  6. Chloride channel protein ClC-Kb

Tbio Chloride channel protein ClC-Kb

Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.

The protein encoded by this gene is a member of the family of voltage-gated chloride channels. Chloride channels have several functions, including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport. This gene is expressed predominantly in the kidney and may be important for renal salt reabsorption. Mutations in this gene are associated with autosomal recessive Bartter syndrome type 3 (BS3). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

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Property Summary

NCBI Gene PubMed Count 51
PubMed Score 92.69
PubTator Score 97.49

Knowledge Summary

Patent (2,776)

TINX Plot

  Disease (5)

Disease Target Count P-value
psoriasis 6685 9.5e-13
pituitary cancer 1972 2.0e-03

Expression

  Differential Expression (2)

Disease log2 FC p
pituitary cancer 1.400 2.0e-03
psoriasis -1.200 9.5e-13

Synonym

Accession P51801 B3KUY3 Q5T5Q7 Q5T5Q8 Chloride channel Kb
Symbols CLCKB
ClC-K2
ClC-Kb

Gene

CLCNKB

PANTHER Protein Class (3)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG Inparanoid

 UniProt Keyword (22)

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 GO Function (3)

 GO Component (3)

 GO Process (4)

 Compartment GO Term (19)

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 OMIM Phenotype (2)

 MGI Phenotype (2)

 HCA RNA Cell Line (30)

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Pathway (4)

Protein-protein Interaction (1)

BSND  

Gene RIF (44)

PMID Text
26770037 Five patients had 1 or more mutations in CLCNKB, of whom 3 had homozygous mutations and 2 had single heterozygous mutations and only in CLCNKB had hypocalciuria.
26453302 results demonstrate that the carboxyl terminus of hClC-Kb is not part of the binding site for barttin, but functionally modifies the interplay with barttin.
26063802 These results demonstrate that mutations in a cluster of hydrophobic residues within transmembrane domain 1 affect barttin-CLC-K interaction and impair gating modification by the accessory subunit
26013830 R8W and G47R, two naturally occurring barttin mutations identified in patients with Bartter syndrome type IV, reduce barttin palmitoylation and CLC-K/barttin channel activity.
25923035 Case Report: 2 mutations in the CLCNKB gene, leading to a molecular diagnosis of Bartter syndrome type III in case of sudden infant death.
25919862 Single loci of tag Single Nucleotide Polymorphisms of CLCNKA_B are not enough to increase the Essential Hypertension susceptibility, the combination of CLCNKA SNP, salt, marine products, meat, edible oil consumption is associated with elevated risk
24863058 HEK293 cells the potentiating effect of niflumic acid (NFA) on CLC-Ka/barttin and CLC-Kb/barttin channels seems to be absent while the blocking efficacy of niflumic acid and benzofuran derivatives observed in oocytes is preserved
24271511 we report here for the first time that ClC-Kb disease-causing mutations located around the selectivity filter can result in both reduced surface expression and hyperactivity in heterologous expression systems
23703872 study investigated the functional consequences of seven mutations; four mutants carried no current whereas others displayed a 30-60 percent reduction in conductance as compared with wild-type ClC-Kb
23345488 This article presents the case of a patient with hypokalaemia caused by CLCNKB gene mutation hard to categorise as GS or BS type 3.
22578033 expands the association between CLCNKB and essential hypertension to a non-European ancestry population
21865213 CLCNKB mutations are associated with Bartter syndrome.
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
21631963 four mutations in the CLCNKB gene, among patients suffering from bartter and Gitelman syndromes
21479528 novel missense variant of the CLCNKB gene in two patients with type III Bartter syndrome
20805576 Identify a protein region that is involved in calcium binding and that is likely undergoing conformational changes underlying the complex gating of CLC-K channels.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19807735 Three novel CLCNKB mutations are identified associated with classic Bartter syndrome with a role in altering the functional properties of ClC-Kb channels.
19226700 Threonine change to serine at position 481 in CLCNKB is associated with essential hypertension in males within the Ghanaian population.
19226700 Observational study of gene-disease association. (HuGE Navigator)
19096086 In a large cohort of ante/neonatal Bartter syndrome, deafness, transient hyperkalaemia and severe hypokalaemic hypochloraemic alkalosis orientate molecular investigations to BSND, KCNJ1 and CLCNKB genes, respectively.
19058262 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
18648499 ClC-Ka and ClC-Kb differ in how conformational changes are translated to the extracellular domain, despite the fact that the cytoplasmic domains share the same quaternary structure
18094726 Disruption of the gene encoding Barttin, BSND, results in a 'double knockout' of the functions of both ClCKA and ClCKB, manifesting as Bartter syndrome type IV with sensorineural deafness and an especially severe salt-losing phenotype.
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
17997379 Observational study of gene-disease association. (HuGE Navigator)
17652939 Observational study of genotype prevalence. (HuGE Navigator)
17622951 Results identify large heterozygous deletion mutations in the CLCNKB gene in patients with type III Bartter syndrome.
17510212 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
17143181 Observational study of gene-disease association. (HuGE Navigator)
17137217 Observational study of gene-disease association. (HuGE Navigator)
16902263 Identification of a novel mutation of the CLCNKB gene, DeltaL130 associated with Bartter syndrome.
16849430 Barttin modulates trafficking and function of ClC-K1 and ClC-Kb channels
16391491 confirms a weak genotype-phenotype correlation in patients with CLCNKB mutations and supports the founder effect of the A204T mutation in Spain
16003175 Observational study of gene-disease association. (HuGE Navigator)
16003175 There is no association with hypertension of CLCNKB polymorphism at a hypertension locus on chromosome 1p36.
15671602 Observational study of genotype prevalence and gene-disease association. (HuGE Navigator)
15148291 The mutation ClC-Kb(T481S) of the renal epithelial Cl- channel ClC-Kb strongly activates ClC-Kb chloride channel function in vitro and may predispose to the development of essential hypertension in vivo.
15044642 Combined impairment of ClC-Ka and ClC-Kb results in phenotype that mimics neonatal Barrter's syndrome with deafness
14675050 Genetic heterogeneity of ClC-Kb chloride channels correlates with functional heterogeneity, which assigns ClC-Kb to a set of genes potentially relevant for polygenic salt-sensitivity of blood pressure regulation.
14502078 CLCKB expression is demonstrated in stria vascularis, spiral ligament and limbal fibrocytes, interdental cells and satellite cells of spiral ganglion neurons of mice harboring enhanced green fluorescence protein gene driven by the human CLCKB promoter.
12472765 presence of Gitelman and Bartter syndrome and CBS phenotypes, in a kindred with the CLCNKB R438H mutation.
11865110 DNA mutational analysis of CLCNKB in Bartter syndrome type 3.

AA Sequence 

MEEFVGLREGSSGNPVTLQELWGPCPRIRRGIRGGLEWLKQKLFRLGEDWYFLMTLGVLMALVSCAMDLA      1 - 70
VESVVRAHQWLYREIGDSHLLRYLSWTVYPVALVSFSSGFSQSITPSSGGSGIPEVKTMLAGVVLEDYLD     71 - 140
IKNFGAKVVGLSCTLACGSTLFLGKVGPFVHLSVMMAAYLGRVRTTTIGEPENKSKQNEMLVAAAAVGVA    141 - 210
TVFAAPFSGVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLLAVFNSEQETITSLYKTSFRVDVPFDLP    211 - 280
EIFFFVALGGLCGILGSAYLFCQRIFFGFIRNNRFSSKLLATSKPVYSALATLVLASITYPPSAGRFLAS    281 - 350
RLSMKQHLDSLFDNHSWALMTQNSSPPWPEELDPQHLWWEWYHPRFTIFGTLAFFLVMKFWMLILATTIP    351 - 420
MPAGYFMPIFVYGAAIGRLFGETLSFIFPEGIVAGGITNPIMPGGYALAGAAAFSGAVTHTISTALLAFE    421 - 490
VTGQIVHALPVLMAVLAANAIAQSCQPSFYDGTVIVKKLPYLPRILGRNIGSHRVRVEHFMNHSITTLAK    491 - 560
DMPLEEVVKVVTSTDVAKYPLVESTESQILVGIVRRAQLVQALKAEPPSWAPGHQQCLQDILAAGCPTEP    561 - 630
VTLKLSPETSLHEAHNLFELLNLHSLFVTSRGRAVGCVSWVEMKKAISNLTNPPAPK                 631 - 687
//

Text Mined References (53)

PMID Year Title
26770037 2016 Mutations in SLC12A3 and CLCNKB and Their Correlation with Clinical Phenotype in Patients with Gitelman and Gitelman-like Syndrome.
26453302 2015 Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking.
26063802 2015 Tryptophan Scanning Mutagenesis Identifies the Molecular Determinants of Distinct Barttin Functions.
26013830 2015 Human CLC-K Channels Require Palmitoylation of Their Accessory Subunit Barttin to Be Functional.
25923035 Whole-Exome Sequencing Reveals CLCNKB Mutations in a Case of Sudden Unexpected Infant Death.
25919862 2015 Associations between CLCNKA_B tag SNPs with essential hypertension and interactions between genetic and environmental factors in an island population in China.
24863058 2014 Targeting kidney CLC-K channels: pharmacological profile in a human cell line versus Xenopus oocytes.
24271511 2014 CLCNKB mutations causing mild Bartter syndrome profoundly alter the pH and Ca2+ dependence of ClC-Kb channels.
23703872 2013 Novel CLCNKB mutations causing Bartter syndrome affect channel surface expression.
23345488 2013 Gitelman or Bartter type 3 syndrome? A case of distal convoluted tubulopathy caused by CLCNKB gene mutation.
22578033 2012 Association of CLCNKB haplotypes and hypertension in Mongolian and Han populations.
21865213 2012 Genetic basis of Bartter syndrome in Korea.
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.
21631963 2011 DNA analysis of renal electrolyte transporter genes among patients suffering from Bartter and Gitelman syndromes: summary of mutation screening.
21479528 2011 Bartter syndrome in two sisters with a novel mutation of the CLCNKB gene, one with deafness.
20805576 2010 A regulatory calcium-binding site at the subunit interface of CLC-K kidney chloride channels.
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.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19807735 2010 Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome.
19226700 2009 CLCNKB-T481S and essential hypertension in a Ghanaian population.
19096086 2009 Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome.
19058262 2009 Allelic-based gene-gene interaction associated with quantitative traits.
18648499 2008 A cytoplasmic domain mutation in ClC-Kb affects long-distance communication across the membrane.
18310267 2008 Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness.
18094726 2008 Mechanisms of Disease: the kidney-specific chloride channels ClCKA and ClCKB, the Barttin subunit, and their clinical relevance.
17997379 2008 Association study of variants in two ion-channel genes (TSC and CLCNKB) and hypertension in two ethnic groups in Northwest China.
17652939 2008 Haplotype diversity in four genes (CLCNKA, CLCNKB, BSND, NEDD4L) involved in renal salt reabsorption.
17622951 2007 Molecular analysis of patients with type III Bartter syndrome: picking up large heterozygous deletions with semiquantitative PCR.
17510212 2007 Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension.
17143181 2007 The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes.
17137217 2006 Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension.
16902263 2006 Molecular analysis of the CLCNKB gene in Japanese patients with classic Bartter syndrome.
16849430 2006 Barttin modulates trafficking and function of ClC-K channels.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16391491 2006 A Spanish founder mutation in the chloride channel gene, CLCNKB, as a cause of atypical Bartter syndrome in adult age.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16003175 2005 No association with hypertension of CLCNKB and TNFRSF1B polymorphisms at a hypertension locus on chromosome 1p36.
15671602 2005 Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population--the Suita Study.
15531551 2004 Novel mutations of the chloride channel Kb gene in two Japanese patients clinically diagnosed as Bartter syndrome with hypocalciuria.
15148291 2004 Activating mutation of the renal epithelial chloride channel ClC-Kb predisposing to hypertension.
15044642 2004 Salt wasting and deafness resulting from mutations in two chloride channels.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14675050 2004 A common sequence variation of the CLCNKB gene strongly activates ClC-Kb chloride channel activity.
14502078 2003 Expression of CLC-KB gene promoter in the mouse cochlea.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12472765 2003 A novel mutation in the chloride channel gene, CLCNKB, as a cause of Gitelman and Bartter syndromes.
11734858 2001 Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion.
11102542 2000 Mutations in the chloride channel gene, CLCNKB, leading to a mixed Bartter-Gitelman phenotype.
10906158 2000 Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome.
9326936 1997 Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III.
8812470 1996 Assignment of the genes encoding the human chloride channels, CLCNKA and CLCNKB, to 1p36 and of CLCN3 to 4q32-q33 by in situ hybridization.
8544406 1995 Cloning, tissue distribution, and intrarenal localization of ClC chloride channels in human kidney.
8041726 1994 Two highly homologous members of the ClC chloride channel family in both rat and human kidney.