CHAC2
Chr 2ChaC glutathione specific gamma-glutamylcyclotransferase 2
Also known as: GCG1
The gamma-glutamyl cyclotransferase CHAC2 catalyzes the cleavage of glutathione into 5-oxo-L-proline and cysteinyl-glycine, and is upregulated during endoplasmic reticulum stress to promote apoptosis through glutathione depletion. Mutations cause autosomal recessive early infantile epileptic encephalopathy, characterized by severe seizures and developmental delays beginning in infancy. This gene is highly intolerant to loss-of-function variants, suggesting that complete loss of function is likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
66 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 | 0 | 0 | 9 | 0 | 9 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 47 | 2 | 0 | 49 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 47 | 13 | 0 | 60 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CHAC2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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