CLCNKB chloride voltage-gated channel Kb [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLCNKBprovided by HGNC
Official Full Name: chloride voltage-gated channel Kbprovided by HGNC
Primary source: HGNC:HGNC:2027
See related: Ensembl:ENSG00000184908 MIM:602023; AllianceGenome:HGNC:2027
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CLCKB; ClC-K2; ClC-Kb
Summary: 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]
Expression: Biased expression in kidney (RPKM 65.3), salivary gland (RPKM 9.9) and 1 other tissue See more
Orthologs: all
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Genomic context

Location:: 1p36.13

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (16043782..16057326)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (15485085..15498707)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (16370277..16383821)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Expanding Genotype-Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss.
Title: Expanding Genotype-Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss.
Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions.
Title: Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions.
A novel CLCNKB variant in a Chinese family with classic Bartter syndrome and prenatal genetic diagnosis.
Title: A novel CLCNKB variant in a Chinese family with classic Bartter syndrome and prenatal genetic diagnosis.
Simultaneous Homozygous Mutations in SLC12A3 and CLCNKB in an Inbred Chinese Pedigree.
Title: Simultaneous Homozygous Mutations in SLC12A3 and CLCNKB in an Inbred Chinese Pedigree.
Analysis of CLCNKB mutations at dimer-interface, calcium-binding site, and pore reveals a variety of functional alterations in ClC-Kb channel leading to Bartter syndrome.
Title: Analysis of CLCNKB mutations at dimer-interface, calcium-binding site, and pore reveals a variety of functional alterations in ClC-Kb channel leading to Bartter syndrome.
Thirteen novel CLCNKB variants and genotype/phenotype association study in 42 Chinese patients with Bartter syndrome type 3.
Title: Thirteen novel CLCNKB variants and genotype/phenotype association study in 42 Chinese patients with Bartter syndrome type 3.
Nine variants in the chloride voltagegated channel Kb (CLCNKB) gene were detected, including eight sequence variants and one whole CLCNKB gene deletion. One sequence variant (c.1967T>C) was novel, whereas the remaining variants (c.595G>T, c.908A>C, c.1004T>C, c.1312C>T, c.1334_1335delCT and c.1718C>A) and the whole gene deletion had been previously reported.
Title: A novel mutation associated with Type III Bartter syndrome: A report of five cases.
Bartter syndrome (BS) is a rare autosomal recessive disorder of salt reabsorption at the thick ascending limb of the Henle loop, characterized by hypokalemia, salt loss, metabolic alkalosis, hyperreninemic hyperaldosteronism with normal blood pressure. BS type III, often known as classic BS (CBS), is caused by loss-of-function mutations in CLCNKB (chloride voltage-gated channel Kb) encoding basolateral ClC-Kb.
Title: A novel CLCNKB mutation in a Chinese girl with classic Bartter syndrome: a case report.
results suggested that the compound defective mutations of the CLCNKB gene are the molecular mechanism of the two classic Bartter syndrome siblings
Title: Novel compound heterozygous CLCNKB gene mutations (c.1755A>G/c.848_850delTCT) cause classic Bartter syndrome.
Taking advantage of the largest number of functional results of CLCNKB mutations, we reveal the functionally important domains and severe mutational spots of the hClC-Kb channel and establish the genotype-phenotype association in classic Bartter's Syndrome.
Title: Functional severity of CLCNKB mutations correlates with phenotypes in patients with classic Bartter's syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (49)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Bartter disease type 3 MedGen: C1846343 OMIM: 607364 GeneReviews: Not available	not available
Bartter disease type 4B MedGen: C4310805 OMIM: 613090 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables voltage-gated chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in chloride transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in renal absorption	TAS Traceable Author Statement more info	PubMed
involved_in renal sodium ion absorption	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transepithelial chloride transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of chloride channel complex	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: chloride channel protein ClC-Kb

Names: chloride channel, kidney, B; chloride channel, voltage-sensitive Kb

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013079.2 RefSeqGene

Range

5002..18528

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000085.5 → NP_000076.2 chloride channel protein ClC-Kb isoform 1

See identical proteins and their annotated locations for NP_000076.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL355994

Consensus CDS

CCDS168.1

UniProtKB/Swiss-Prot

B3KUY3, P51801, Q5T5Q7, Q5T5Q8

UniProtKB/TrEMBL

A0A804HJB2

Related

ENSP00000364831.5, ENST00000375679.9

Conserved Domains (3) summary

cd03683
Location:49 → 534

ClC_1_like; ClC-1-like chloride channel proteins. This CD includes isoforms ClC-0, ClC-1, ClC-2 and ClC_K. ClC-1 is expressed in skeletal muscle and its mutation leads to both recessively and dominantly-inherited forms of muscle stiffness or myotonia. ClC-K is ...

cd04591
Location:555 → 676

CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...

pfam00654
Location:106 → 513

Voltage_CLC; Voltage gated chloride channel
NM_001165945.2 → NP_001159417.2 chloride channel protein ClC-Kb isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has a different 5' UTR, uses an alternate splice site in the 3' coding region, and initiates translation from a different start codon compared to variant 1. This results in a shorter isoform (2) with a distinct N-terminus compared to isoform 1.

Source sequence(s)

AK098217, AL355994, DA369686, DA424588

Consensus CDS

CCDS57974.1

UniProtKB/Swiss-Prot

P51801

Related

ENSP00000364819.3, ENST00000375667.7

Conserved Domains (3) summary

cd04591
Location:386 → 506

CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...

pfam00654
Location:50 → 344

Voltage_CLC; Voltage gated chloride channel

cl02915
Location:50 → 365

Voltage_gated_ClC; CLC voltage-gated chloride channel. The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. This ...