CLCN7

Chr 16

Cl-/H+ antiporter 7

Also known as: CLC-7, CLC7, HOD, OPTA2, OPTB4, PPP1R63

NCBI Gene: 1186 ENSG00000103249 UniProt: P51798

Chloride channel 7 is a slowly voltage-gated channel that exchanges chloride ions for protons, contributing to lysosomal acidification and pH maintenance. Mutations cause osteopetrosis with abnormally dense bones due to defective bone resorption, presenting as severe infantile malignant osteopetrosis in the autosomal recessive form or milder adolescent/adult-onset disease in the autosomal dominant form. Some patients also develop hypopigmentation, organomegaly, and delayed myelination with developmental delays.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtOsteopetrosis, autosomal recessive 4

UniProtOsteopetrosis, autosomal dominant 2

UniProtHypopigmentation, organomegaly, and delayed myelination and development

Clinical highlights

Gene-disease validity (ClinGen)

autosomal dominant osteopetrosis 2 · ADDefinitivesufficient evidence for diagnostic panels3 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

LOF

Mechanism· G2P

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GeneReview available — CLCN7