CHAC1
Basic information
Region (hg38): 15:40952962-40956512
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (37 variants)
- not_provided (1 variants)
- Prostate_cancer (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHAC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024111.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 35 | 35 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 36 | 1 | 0 |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CHAC1 | protein_coding | protein_coding | ENST00000446533 | 3 | 3551 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000206 | 0.745 | 125716 | 0 | 22 | 125738 | 0.0000875 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.244 | 152 | 161 | 0.946 | 0.00000859 | 1677 |
| Missense in Polyphen | 51 | 64.044 | 0.79633 | 679 | ||
| Synonymous | -0.221 | 73 | 70.6 | 1.03 | 0.00000421 | 564 |
| Loss of Function | 1.00 | 7 | 10.5 | 0.666 | 5.43e-7 | 97 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000177 | 0.000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000327 | 0.000326 |
dbNSFP
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 (PubMed:27913623). Glutathione depletion is an important factor for apoptosis initiation and execution. Acts as a pro-apoptotic component of the unfolded protein response pathway by mediating the pro-apoptotic effects of the ATF4-ATF3-DDIT3/CHOP cascade (PubMed:19109178). Negative regulator of Notch signaling pathway involved in embryonic neurogenesis: acts by inhibiting Notch cleavage by furin, maintaining Notch in an immature inactive form, thereby promoting neurogenesis in embryos (PubMed:22445366). {ECO:0000269|PubMed:19109178, ECO:0000269|PubMed:22445366, ECO:0000269|PubMed:27913623}.;
- Pathway
- Glutathione conjugation;Phase II - Conjugation of compounds;Biological oxidations;Metabolism;Glutathione synthesis and recycling
(Consensus)
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- loftool
- 0.393
- rvis_EVS
- 0.86
- rvis_percentile_EVS
- 88.69
Haploinsufficiency Scores
- pHI
- 0.469
- hipred
- N
- hipred_score
- 0.238
- ghis
- 0.396
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.600
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Chac1
- Phenotype
Gene ontology
- Biological process
- glutathione biosynthetic process;glutathione catabolic process;response to unfolded protein;Notch signaling pathway;negative regulation of protein processing;neurogenesis;negative regulation of Notch signaling pathway;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
- Cellular component
- cytoplasm;trans-Golgi network;cytosol
- Molecular function
- gamma-glutamylcyclotransferase activity;Notch binding;protein binding;glutathione specific gamma-glutamylcyclotransferase activity