CLCN7

Protein identityUniProt · HPA

UniProt accession

P51798

Gene

CLCN7

Ensembl

ENSG00000103249

Chromosome

16

Canonical length

805 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

805 residues, UniProt reviewed canonical sequence.

>P51798|CLCN7
     1  MANVSKKVSW SGRDRDDEEA APLLRRTARP GGGTPLLNGA GPGAARQSPR SALFRVGHMS
    61  SVELDDELLD PDMDPPHPFP KEIPHNEKLL SLKYESLDYD NSENQLFLEE ERRINHTAFR
   121  TVEIKRWVIC ALIGILTGLV ACFIDIVVEN LAGLKYRVIK GNIDKFTEKG GLSFSLLLWA
   181  TLNAAFVLVG SVIVAFIEPV AAGSGIPQIK CFLNGVKIPH VVRLKTLVIK VSGVILSVVG
   241  GLAVGKEGPM IHSGSVIAAG ISQGRSTSLK RDFKIFEYFR RDTEKRDFVS AGAAAGVSAA
   301  FGAPVGGVLF SLEEGASFWN QFLTWRIFFA SMISTFTLNF VLSIYHGNMW DLSSPGLINF
   361  GRFDSEKMAY TIHEIPVFIA MGVVGGVLGA VFNALNYWLT MFRIRYIHRP CLQVIEAVLV
   421  AAVTATVAFV LIYSSRDCQP LQGGSMSYPL QLFCADGEYN SMAAAFFNTP EKSVVSLFHD
   481  PPGSYNPLTL GLFTLVYFFL ACWTYGLTVS AGVFIPSLLI GAAWGRLFGI SLSYLTGAAI
   541  WADPGKYALM GAAAQLGGIV RMTLSLTVIM MEATSNVTYG FPIMLVLMTA KIVGDVFIEG
   601  LYDMHIQLQS VPFLHWEAPV TSHSLTAREV MSTPVTCLRR REKVGVIVDV LSDTASNHNG
   661  FPVVEHADDT QPARLQGLIL RSQLIVLLKH KVFVERSNLG LVQRRLRLKD FRDAYPRFPP
   721  IQSIHVSQDE RECTMDLSEF MNPSPYTVPQ EASLPRVFKL FRALGLRHLV VVDNRNQVVG
   781  LVTRKDLARY RLGKRGLEEL SLAQT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CLCN7 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

10

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CLCN7.

Disease | AllUniProt

Conditions CLCN7 is implicated in, by any mechanism.

• Osteopetrosis, autosomal recessive 4 (OPTB4) MIM:611490
• Osteopetrosis, autosomal dominant 2 (OPTA2) MIM:166600
• Hypopigmentation, organomegaly, and delayed myelination and development (HOD) MIM:618541

Disease | GeneticClinVar

95 pathogenic / likely-pathogenic of 1,464 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive osteopetrosis 4
• Autosomal dominant osteopetrosis 2
• Hypopigmentation, organomegaly, and delayed myelination and development
• CLCN7-related disorder
• Disorder of bone

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.39

gnomAD pLI

0.27

gnomAD missense Z

2.11

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• chloride transmembrane transport
• response to pH
• transepithelial chloride transport

Molecular functions

• ATP binding
• chloride channel activity
• chloride:proton antiporter activity

Cellular components

• chloride channel complex
• lysosomal membrane
• membrane

Protein domainsUniProt · Pfam · InterPro

• CBS domain
• Chloride channel
• Chloride channel, core
• CBS domain superfamily
• Voltage-gated chloride channel/antiporter
• CBS domain
• Voltage gated chloride channel
• H(+)/Cl(-) exchange transporter 7

KeywordsUniProt

• Antiport
• ATP-binding
• CBS domain
• Chloride
• Ion transport
• Lysosome
• Membrane
• Nucleotide-binding
• Osteopetrosis
• Phosphoprotein
• Repeat
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of CLCN7 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• OSTM1
• SLC15A4