CLCN2
Chr 3ADARchloride voltage-gated channel 2
Also known as: CIC-2, CLC2, ECA2, ECA3, EGI11, EGI3, EGMA, EJM6
This gene encodes a voltage-gated chloride channel that maintains chloride ion homeostasis and regulates neuronal excitability, aldosterone production in adrenal glands, and chloride flux in glial cells. Mutations cause leukoencephalopathy with ataxia, familial hyperaldosteronism type II, and susceptibility to various epilepsy syndromes including juvenile absence epilepsy and juvenile myoclonic epilepsy. Inheritance follows both autosomal dominant and autosomal recessive patterns depending on the specific condition.
Refuted — evidence has disproved this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
300 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 7 | 0 | 7 | 0 | 14 |
Likely Pathogenic | 8 | 0 | 0 | 0 | 8 |
VUS | 3 | 154 | 14 | 7 | 178 |
Likely Benign | 0 | 3 | 32 | 35 | 70 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 2 | |||
| Total | 18 | 157 | 55 | 42 | 274 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CLCN2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools