CLCN7

CLCN7 encodes ClC-7, a member of the CLC family that functions as an electrogenic 2Cl(-)/1H(+) antiporter (exchanger) rather than a passive chloride channel. It resides in the membranes of late endosomes and lysosomes, and in osteoclasts it localizes to the ruffled border bounding the resorption lacuna. ClC-7 forms an obligate heteromeric complex with the accessory beta-subunit OSTM1, which is required for ClC-7 protein stability and transport activity. By coupling chloride flux to the outwardly directed proton gradient, ClC-7 provides the counter-ion movement that allows the V-ATPase to acidify the lysosomal lumen and the osteoclast resorption space, and it raises luminal chloride concentration. Loss-of-function variants cause osteopetrosis (recessive OPTB4 and dominant Albers-Schonberg OPTA2) together with lysosomal storage and neurodegeneration, whereas certain gain-of-function variants cause a distinct hypopigmentation, organomegaly and delayed-myelination syndrome.

Disorders

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