CHAC1: ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1
Key regulator of glutathione homeostasis, ER stress response, and apoptosis
Gene Information Card
| Symbol | CHAC1 |
|---|---|
| Full Name | ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.1 |
| NCBI Gene ID | 79094 ncbi.nlm.nih.gov/gene/79094 |
| Ensembl ID | ENSG00000128965 |
| UniProt ID | Q9BUX1 |
| OMIM ID | 615696 |
| HGNC ID | 28680 |
| Aliases | ChaC1, GLX5, MGC4504 |
Description
CHAC1 encodes an enzyme that specifically degrades glutathione by catalyzing the cleavage of the gamma-glutamyl bond, releasing 5-oxoproline and a cysteinylglycine dipeptide. It is a key mediator of the unfolded protein response (UPR) and ER stress-induced apoptosis. CHAC1 expression is induced by ATF4 and ATF3 under conditions of ER stress, and its activity promotes cell death by depleting intracellular glutathione, leading to oxidative stress. The gene is also implicated in the regulation of cellular redox balance and has been studied in cancer, neurodegenerative diseases, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | CHAC1-mediated glutathione depletion promotes apoptosis in response to ER stress; dysregulation may contribute to chemoresistance | COSMIC; PubMed studies |
| Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's) | ER stress-induced CHAC1 upregulation leads to glutathione loss and oxidative neuronal damage | NCBI Gene; PubMed |
| Metabolic disorders (e.g., diabetes) | CHAC1 involvement in ER stress pathways may affect insulin resistance and beta-cell survival | OMIM; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Brain | 4.1 | Low |
| Heart | 3.2 | Low |
| Lung | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression under ER stress |
| HeLa | 10.1 | Induced by tunicamycin |
| HepG2 | 9.5 | Basal expression |
| SH-SY5Y | 6.8 | Low basal, induced by thapsigargin |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Likely loss of function; start codon loss |
| c.200C>T (p.Pro67Leu) | Missense | Rare | Unknown functional effect |
| c.400G>A (p.Glu134Lys) | Missense | Rare | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair CHAC1 enzymatic activity or expression reduce glutathione degradation, potentially protecting cells from oxidative stress but also impairing ER stress-induced apoptosis.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; overexpression of wild-type CHAC1 is sufficient to induce glutathione depletion and cell death.
Dominant Negative (DN)
No dominant-negative mutations described in the literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Unfolded Protein Response (UPR) - ATF4/ATF3 signaling
• Glutathione metabolism
• ER stress-induced apoptosis
Protein Summary
CHAC1 is a 184-amino acid protein (UniProt Q9BUX1) that functions as a gamma-glutamylcyclotransferase specific for glutathione. It catalyzes the conversion of glutathione to 5-oxoproline and cysteinylglycine, thereby depleting cellular glutathione. The protein is localized in the cytoplasm and is strongly induced by ER stress via the PERK-ATF4-CHOP pathway. CHAC1 activity is critical for promoting apoptosis under unresolved ER stress, and its dysregulation is linked to cancer progression, neurodegeneration, and metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHAC1 Knockout HEK293 Cell Line | EDJ-KQ12902 | Human | 79094 | Details Get a Quote |
| CHAC1 Knockout A-549 Cell Line | EDJ-KQ42084 | Human | 79094 | Details Get a Quote |
| CHAC1 Knockout HCT 116 Cell Line | EDJ-KQ42085 | Human | 79094 | Details Get a Quote |
| CHAC1 Knockout HeLa Cell Line | EDJ-KQ42086 | Human | 79094 | Details Get a Quote |
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