CLCC1
Function
Anion-selective channel with Ca(2+)-dependent and voltage-independent gating. Permeable to small monovalent anions with selectivity for bromide > chloride > nitrate > fluoride (By similarity). Operates in the endoplasmic reticulum (ER) membrane where it mediates chloride efflux to compensate for the loss of positive charges from the ER lumen upon Ca(2+) release. Contributes to the maintenance of ER Ca(2+) pools and activation of unfolded protein response to prevent accumulation of misfolded proteins in the ER lumen. Particularly involved in ER homeostasis mechanisms underlying motor neurons and retinal photoreceptors survival (By similarity) (PubMed:25698737, PubMed:30157172, PubMed:37142673).
Involvement in disease
Retinitis pigmentosa 32
RP32
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP32 inheritance is autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Rare variants in CLCC1 may be associated with amyotrophic lateral sclerosis.
Sequence Similarities
Belongs to the chloride channel MCLC family.
Tissue Specificity
Expressed in the retina of the eye, with extensive expression in the lamina cribrosa, optic nerve, ganglion cell layer, inner nuclear layer, outer nuclear layer and retinal pigment epithelium.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Within the endoplasmic reticulum (ER), localizes to the mitochondria-associated ER membrane, a zone of contact between the ER and mitochondrial membranes. Enriched in the rough ER.
Alternative names
KIAA0761, MCLC, CLCC1, Chloride channel CLIC-like protein 1, ER anion channel 1, Mid-1-related chloride channel protein, ERAC1