CLCN3
Domain
Isoform 2 contains a C-terminal PDZ-binding motif mediating the interaction with GOPC.
Function
Isoform 1
Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (By similarity). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (PubMed:29845874). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (PubMed:29845874).
Isoform 2
Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons.
Involvement in disease
Neurodevelopmental disorder with hypotonia and brain abnormalities
NEDHYBA
An autosomal dominant disorder characterized by onset in infancy or early childhood, global developmental delay, hypotonia, impaired intellectual development, and poor or absent speech. Additional variable manifestations may be present, including feeding difficulties, seizures, behavioral abnormalities, and non-specific dysmorphic facial features. Brain imaging shows variable abnormalities, including corpus callosum and cerebellar defects, and decreased white matter volume.
None
The disease is caused by variants affecting the gene represented in this entry.
Neurodevelopmental disorder with seizures and brain abnormalities
NEDSBA
An autosomal recessive neurologic disorder characterized by global developmental delay and onset of seizures in the first months of life, and structural brain defects on brain imaging. Additional features may include pigmentary retinopathy with poor visual fixation and spasticity.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the chloride channel (TC 2.A.49) family. ClC-3/CLCN3 subfamily.
Tissue Specificity
Expressed primarily in tissues derived from neuroectoderm. Within the brain, its expression is particularly evident in the hippocampus, olfactory cortex, and olfactory bulb. Highly expressed in aortic and coronary vascular smooth muscle cells, and aortic endothelial cells. Also expressed in tracheal and alveolar epithelial cells, and intima and media of the pulmonary vessels. Expressed in bronchus and colon (at protein level).
Cellular localization
- Isoform 1
- Early endosome membrane
- Multi-pass membrane protein
- Late endosome membrane
- Multi-pass membrane protein
- Lysosome membrane
- Multi-pass membrane protein
- Cell membrane
- Multi-pass membrane protein
- Isoform 1 is localized mainly in late endosomes.
- Isoform 2
- Golgi apparatus membrane
- Multi-pass membrane protein
- Cell projection
- Ruffle membrane
- Multi-pass membrane protein
- Isoform 2 is mainly enriched in the Golgi (PubMed:12471024). Colocalizes with NHERF1/EBP50 in membrane ruffles (PubMed:11967229).
Alternative names
H(+)/Cl(-) exchange transporter 3, Chloride channel protein 3, Chloride transporter ClC-3, ClC-3, CLCN3