CHAC2
protein-codingChaC glutathione specific gamma-glutamylcyclotransferase 2
Gene summary
The protein encoded by this gene is a gamma-glutamyl cyclotransferase that catalyzes the conversion of glutathione to 5-oxoproline and cysteinylglycine. It is thought that this gene is upregulated in response to endoplasmic reticulum stress and that the glutathione depletion enhances apoptosis. [provided by RefSeq, Sep 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CHAC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001008708.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 47 | 47 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 51 | 0 | 0 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001008708.1 | 3 | MANE Select | |
| Ensembl | ENSP00000295304.4 | 3 | MANE Select | |
| RefSeq | NP_001333056.1 | 2 | Standard | |
| Ensembl | ENSP00000563917.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutathione conjugation
- Phase II - Conjugation of compounds
- Biological oxidations
- Metabolism
- Glutathione synthesis and recycling
Biological Process
- glutathione biosynthetic process
- glutathione catabolic process
- biological_process
Molecular Function
- molecular_function
- gamma-glutamylcyclotransferase activity
- glutathione specific gamma-glutamylcyclotransferase activity
Cellular Component
- cellular_component
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295304
- Coding exons
- 3
- Length
- 7405
- Individuals with no LoFs
- 125660
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 88
- Defined
- 125748
- p
- 0.000350
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.18 | 131 | 98.0 | 1.34 | 0.00000456 | 1193 |
| Missense (PolyPhen) | 43 | 32.143 | 1.3378 | 396 | ||
| Synonymous | -1.28 | 44 | 34.4 | 1.28 | 0.00000156 | 354 |
| Loss of Function | -0.382 | 8 | 6.92 | 1.16 | 2.89e-7 | 93 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00031 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00062 | 0.00062 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the cleavage of glutathione into 5-oxo-L- proline and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on other gamma-glutamyl peptides. {ECO:0000269|PubMed:27913623}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- LoFtool
- 0.735
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.35
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |