CLCNKA chloride voltage-gated channel Ka [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLCNKAprovided by HGNC
Official Full Name: chloride voltage-gated channel Kaprovided by HGNC
Primary source: HGNC:HGNC:2026
See related: Ensembl:ENSG00000186510 MIM:602024; AllianceGenome:HGNC:2026
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: CLCK1; ClC-K1; hClC-Ka
Summary: This gene is a member of the CLC family of voltage-gated chloride channels. The encoded protein is predicted to have 12 transmembrane domains, and requires a beta subunit called barttin to form a functional channel. It is thought to function in salt reabsorption in the kidney and potassium recycling in the inner ear. The gene is highly similar to CLCNKB, which is located 10 kb downstream from this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Biased expression in kidney (RPKM 55.9), salivary gland (RPKM 4.5) 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_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (16022036..16034050)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (15463347..15475360)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (16348531..16360545)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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.
Role of PKC in the Regulation of the Human Kidney Chloride Channel ClC-Ka.
Title: Role of PKC in the Regulation of the Human Kidney Chloride Channel ClC-Ka.
Increasing expression of barttin over that of ClC-K partially recovered this insufficiency, indicating that N-terminal modifications of barttin alter both binding affinities and gating properties
Title: Activation of renal ClC-K chloride channels depends on an intact N terminus of their accessory subunit barttin.
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.
Title: Associations between CLCNKA_B tag SNPs with essential hypertension and interactions between genetic and environmental factors in an island population in China.
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.
Title: Human CLC-K Channels Require Palmitoylation of Their Accessory Subunit Barttin to Be Functional.
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
Title: Targeting kidney CLC-K channels: pharmacological profile in a human cell line versus Xenopus oocytes.
following variables were significantly associated with an estimated glomerular filtration rate: age, type 2 diabetes, total cholesterol, LDL-cholesterol, and the CLCNKA GG genotype
Title: A CLCNKA polymorphism (rs10927887; p.Arg83Gly) previously linked to heart failure is associated with the estimated glomerular filtration rate in the RENASTUR cohort.
The variant CLCNKA risk allele, telegraphed by linked variants in the adjacent HSPB7 gene, uncovers a previously overlooked genetic mechanism affecting the cardio-renal axis.
Title: Loss-of-function DNA sequence variant in the CLCNKA chloride channel implicates the cardio-renal axis in interindividual heart failure risk variation.
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.
Title: A regulatory calcium-binding site at the subunit interface of CLC-K kidney chloride channels.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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 4B MedGen: C4310805 OMIM: 613090 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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 identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
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 transepithelial chloride transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
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-Ka

Names: chloride channel Ka; chloride channel, kidney, A; chloride channel, voltage-sensitive Ka

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_009359.1 RefSeqGene

Range

5046..17060

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001042704.2 → NP_001036169.1 chloride channel protein ClC-Ka isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a protein (isoform 2) that is one amino acid shorter than isoform 1.

Source sequence(s)

AK225550, BC053869

Consensus CDS

CCDS41269.1

UniProtKB/TrEMBL

A8K449

Related

ENSP00000364844.1, ENST00000375692.5

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 → 675

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_001257139.2 → NP_001244068.1 chloride channel protein ClC-Ka isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The resulting protein is shorter compared to isoform 1.

Source sequence(s)

AI821546, AK298285, AL355994

Consensus CDS

CCDS57973.1

UniProtKB/TrEMBL

A8K449

Related

ENSP00000414445.2, ENST00000439316.6

Conserved Domains (3) summary

cd03683
Location:49 → 491

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:512 → 633

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:59 → 470

Voltage_CLC; Voltage gated chloride channel
NM_004070.4 → NP_004061.3 chloride channel protein ClC-Ka isoform 1

See identical proteins and their annotated locations for NP_004061.3

Status: REVIEWED

Description

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

Source sequence(s)

BC053869, Z30643

Consensus CDS

CCDS167.1

UniProtKB/Swiss-Prot

B4DPD3, E7EPH6, P51800, Q5T5P8, Q5T5Q4, Q7Z6D1, Q86VT1

UniProtKB/TrEMBL

A8K449

Related

ENSP00000332771.4, ENST00000331433.5

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