CLCN2

This gene encodes a voltage-gated chloride channel. The encoded protein is a transmembrane protein that maintains chloride ion homeostasis in various cells. Defects in this gene may be a cause of certain epilepsies. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

Full Name

chloride channel 2

Function

Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport. Involved in the regulation of aldosterone production. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated Ca2+ channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (PubMed:29403011, PubMed:29403012).

Biological Process

Cell differentiation involved in salivary gland development Source: Ensembl
Chloride transport Source: GO_Central
Ion transmembrane transport Source: Reactome
Regulation of aldosterone biosynthetic process Source: UniProtKB
Regulation of ion transmembrane transport Source: UniProtKB-KW
Retina development in camera-type eye Source: Ensembl

Cellular Location

Cell membrane

Involvement in disease

Epilepsy, idiopathic generalized 11 (EIG11):
A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.
Juvenile absence epilepsy 2 (JAE2):
A subtype of idiopathic generalized epilepsy characterized by onset occurring around puberty, absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures.
Juvenile myoclonic epilepsy 8 (EJM8):
A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue.
Leukoencephalopathy with ataxia (LKPAT):
An autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles, suggesting myelin microvacuolation. Clinical features include ataxia and unstable gait. More variable abnormalities may include visual field defects, headaches, and learning disabilities.
Hyperaldosteronism, familial, 2 (HALD2):
An autosomal dominant disorder characterized by elevated plasma aldosterone level and hypertension of varying severity even within members of the same family. Hypokalemia is observed in some patients. In HALD2, hypertension does not improve with glucocorticoid treatment.

Topology

Cytoplasmic: 2-87
Helical: 88-121
Helical: 130-155
Helical: 164-171
Helical: 180-198
Helical: 205-223
Helical: 239-251
Helical: 255-263
Helical: 275-295
Helical: 321-349
Helical: 358-377
Helical: 429-449
Helical: 457-480
Helical: 497-511
Loop between two helices: 512-513
Helical: 514-525
Loop between two helices: 526-530
Helical: 531-548
Cytoplasmic: 549-898

PTM

Phosphorylated. Activated by dephosphorylation.