CLCN7 chloride voltage-gated channel 7 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLCN7provided by HGNC
Official Full Name: chloride voltage-gated channel 7provided by HGNC
Primary source: HGNC:HGNC:2025
See related: Ensembl:ENSG00000103249 MIM:602727; AllianceGenome:HGNC:2025
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: HOD; CLC7; CLC-7; OPTA2; OPTB4; PPP1R63
Summary: The product of this gene belongs to the CLC chloride channel family of proteins. Chloride channels play important roles in the plasma membrane and in intracellular organelles. This gene encodes chloride channel 7. Defects in this gene are the cause of osteopetrosis autosomal recessive type 4 (OPTB4), also called infantile malignant osteopetrosis type 2 as well as the cause of autosomal dominant osteopetrosis type 2 (OPTA2), also called autosomal dominant Albers-Schonberg disease or marble disease autosoml dominant. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in spleen (RPKM 16.9), kidney (RPKM 15.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p13.3

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (1444935..1475028, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (1459595..1489742, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (1494936..1525029, complement)

Chromosome 16 - NC_000016.10 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?

Multisystem disorder associated with a pathogenic variant in CLCN7 in the absence of osteopetrosis.
Title: Multisystem disorder associated with a pathogenic variant in CLCN7 in the absence of osteopetrosis.
Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease.
Title: Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease.
Impaired Autophagic Clearance with a Gain-of-Function Variant of the Lysosomal Cl[-]/H[+] Exchanger ClC-7.
Title: Impaired Autophagic Clearance with a Gain-of-Function Variant of the Lysosomal Cl(-)/H(+) Exchanger ClC-7.
The Role of the Lysosomal Cl(-)/H(+) Antiporter ClC-7 in Osteopetrosis and Neurodegeneration.
Title: The Role of the Lysosomal Cl(-)/H(+) Antiporter ClC-7 in Osteopetrosis and Neurodegeneration.
CLCN7-related neuropathic infantile osteopetrosis in siblings.
Title: CLCN7-related neuropathic infantile osteopetrosis in siblings.
Pathobiologic Mechanisms of Neurodegeneration in Osteopetrosis Derived From Structural and Functional Analysis of 14 ClC-7 Mutants.
Title: Pathobiologic Mechanisms of Neurodegeneration in Osteopetrosis Derived From Structural and Functional Analysis of 14 ClC-7 Mutants.
Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7-related osteopetrosis.
Title: Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7-related osteopetrosis.
Transcriptomic and bioinformatic analysis of Clcn7-dependent Autosomal Dominant Osteopetrosis type 2. Preclinical and clinical implications.
Title: Transcriptomic and bioinformatic analysis of Clcn7-dependent Autosomal Dominant Osteopetrosis type 2. Preclinical and clinical implications.
Identification and Characterization of a Novel CLCN7 Variant Associated with Osteopetrosis.
Title: Identification and Characterization of a Novel CLCN7 Variant Associated with Osteopetrosis.
Cryo-EM structure of the lysosomal chloride-proton exchanger CLC-7 in complex with OSTM1.
Title: Cryo-EM structure of the lysosomal chloride-proton exchanger CLC-7 in complex with OSTM1.

Submit: New GeneRIF Correction See all GeneRIFs (48)

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
Autosomal dominant osteopetrosis 2 MedGen: C3179239 OMIM: 166600 GeneReviews: CLCN7-Related Osteopetrosis	Compare labs
Autosomal recessive osteopetrosis 4 MedGen: C1969106 OMIM: 611490 GeneReviews: CLCN7-Related Osteopetrosis	Compare labs
Hypopigmentation, organomegaly, and delayed myelination and development MedGen: C5203300 OMIM: 618541 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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Markers

D1S2792 (e-PCR)
- UniSTS:7462

RH102989 (e-PCR)
- UniSTS:97323

RH12098 (e-PCR)
- UniSTS:44080

A005U10 (e-PCR)
- UniSTS:44081

D1S486 (e-PCR), detects polymorphism
- UniSTS:38481

RH77853 (e-PCR)
- UniSTS:37009

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables antiporter activity	IEA Inferred from Electronic Annotation more info
enables chloride channel activity	TAS Traceable Author Statement more info	PubMed
enables chloride transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables voltage-gated chloride channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in transepithelial chloride transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of chloride channel complex	IPI Inferred from Physical Interaction more info	PubMed
is_active_in intracellular membrane-bounded organelle	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosomal membrane	HDA more info	PubMed
is_active_in lysosomal membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed

General protein information

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Preferred Names: H(+)/Cl(-) exchange transporter 7

Names: chloride channel 7 alpha subunit; chloride channel protein 7; chloride channel, voltage-sensitive 7; protein phosphatase 1, regulatory subunit 63

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_007567.1 RefSeqGene

Range

5057..35150

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001114331.3 → NP_001107803.1 H(+)/Cl(-) exchange transporter 7 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (b), that is missing an internal segment compared to isoform a.

Source sequence(s)

AA741117, AK056551, AL031600, DB061109

UniProtKB/TrEMBL

B3KVJ8

Related

ENSP00000262318.8, ENST00000262318.12

Conserved Domains (2) summary

cd03685
Location:71 → 596

ClC_6_like; ClC-6-like chloride channel proteins. This CD includes ClC-6, ClC-7 and ClC-B, C, D in plants. Proteins in this family are ubiquitous in eukarotes and their functions are unclear. They are expressed in intracellular organelles membranes. This family ...

cd04591
Location:602 → 766

CBS_pair_voltage-gated_CLC_euk_bac; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and bacteria
NM_001287.6 → NP_001278.1 H(+)/Cl(-) exchange transporter 7 isoform a

See identical proteins and their annotated locations for NP_001278.1

Status: REVIEWED

Description

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

Source sequence(s)

AA741117, AL031600, AL031705, BC012737

Consensus CDS

CCDS32361.1

UniProtKB/Swiss-Prot

A6NEJ7, A8K5T9, A8K7X1, B3KPN3, E9PDB9, P51798, Q9NYX5

UniProtKB/TrEMBL

B3KVJ8

Related

ENSP00000372193.4, ENST00000382745.9

Conserved Domains (2) summary

cd03685
Location:95 → 620

ClC_6_like; ClC-6-like chloride channel proteins. This CD includes ClC-6, ClC-7 and ClC-B, C, D in plants. Proteins in this family are ubiquitous in eukarotes and their functions are unclear. They are expressed in intracellular organelles membranes. This family ...

cd04591
Location:626 → 790

CBS_pair_voltage-gated_CLC_euk_bac; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and bacteria

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

1444935..1475028 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011522354.2 → XP_011520656.1 H(+)/Cl(-) exchange transporter 7 isoform X1

UniProtKB/TrEMBL

B4E3N4, B7Z9L3

Conserved Domains (4) summary

COG0517
Location:680 → 737

CBS; CBS domain [Signal transduction mechanisms]

cd03685
Location:37 → 562

ClC_6_like; ClC-6-like chloride channel proteins. This CD includes ClC-6, ClC-7 and ClC-B, C, D in plants. Proteins in this family are ubiquitous in eukarotes and their functions are unclear. They are expressed in intracellular organelles membranes. This family ...

cd04591
Location:578 → 732

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:127 → 537

Voltage_CLC; Voltage gated chloride channel