Alt. symbols: CLC-7 | OPTA2 | CLC7 | ClC-7 | PPP1R63

Approved name: chloride voltage-gated channel 7
Alt. names: chloride channel 7, chloride channel, voltage-sensitive 7 | protein phosphatase 1, regulatory subunit 63

Location: 16p13.3: 1444934 - 1475077 (-)
Gene type: protein_coding, 16 transcripts.

Scores: LoFtool: 0.046800 | pLI: 0.98128298 | LOEUF: 0.394

HGNC: 2025

NCBI: 1186, RefSeq: NG_007567.1

Ensembl: ENSG00000103249.19

LRG_ | Status: none

OMIM: 602727

Expression | ProteinAtlas

The CLCN7 gene encodes the chloride ion channel CLC protein family member 7 (CLC-7) alpha subunit, which transmits electrical signals by mediating the flow of chloride ions across cell membranes throughout the body. CLC-7 is highly expressed on osteoclast membranes and regulates the pH of osteoclasts. With this, CLC-7 has an important role in maintaining the acidic environment necessary for osteoclasts to successfully dissolve bone tissue and is needed for the normal function of osteoclasts. Osteoclasts are involved in bone remodeling, which is a constant process in which old bone tissue is degraded and replaced by new and healthy bone tissue.

Mutations in CLCN7 account for approximately 75% of autosomal dominant osteopetrosis [MIM:166600] cases and for 10-15% of autosomal recessive osteopetrosis [MIM:611490] cases (Okamoto et al., 2017). In general, mutations in CLCN7 lead to malfunctioning of osteoclasts, which results in decreased dissolution of bone tissue and overgrowth of bone. The autosomal recessive form presents in early infancy or in fetal life and is generally fatal within the first decade of life. It is associated with var ious clinical manifestations, including macrocephaly, cranial nerve dysfunction causing deafness and blindness, hepatosplenomegaly and severe bone marrow failures. In 2001, it was suggested by Cleiren et al. that the recessive form of osteopetrosis is caused by homozygous or compound heterozygous mutations leading to loss of protein function, whereas the autosomal dominant form is associated with monoallelic dominant-negative or haploinsufficiency mutations. In line with this, homozygous mutations in CLCN7 (D145X, I261F, L766P and R767Q) or mutations in compound heterozygosity, which include the combination of missense/nonsense mutations (Q555X + R762Q, G240R + R526W, M332W + R767W and P249R + S744F) or the occurrence of a missense mutation L614P together with a larger frameshift mutation as well as the occurrence of a nonsense mutation E374X together with an in-frame insertion, have been detected in patients with autosomal recessive osteopetrosis (Cleiren et al., 2001; Kornak et al., 2001; Frattini et al., 2003; Lam et al., 2007). Autosomal dominant osteopetrosis is generally presenting in adulthood with less severe clinical symptoms and has been genetically associated with CLCN7 in patients carrying monoallelic mutations, such as G677V, G215R, L490F, W179X, R286Q, c.2423delAG, P249L, R767W, G765B, L688del or R286W. [Load More]