CPA4
protein-codingcarboxypeptidase A4, the group of M14 carboxypeptidases
Gene summary
This gene is a member of the carboxypeptidase A/B subfamily, and it is located in a cluster with three other family members on chromosome 7. Carboxypeptidases are zinc-containing exopeptidases that catalyze the release of carboxy-terminal amino acids, and are synthesized as zymogens that are activated by proteolytic cleavage. This gene could be involved in the histone hyperacetylation pathway. It is imprinted and may be a strong candidate gene for prostate cancer aggressiveness. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.0 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 CPA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016352.4. 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 | 1 | 1 | 2 | |||
| missense | 61 | 1 | 62 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 63 | 3 | 0 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057436.2 | 11 | MANE Select | |
| Ensembl | ENSP00000222482.4 | 11 | MANE Select | |
| RefSeq | NP_001156918.1 | 10 | Standard | |
| Ensembl | ENSP00000412947.2 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- proteolysis
- histone acetylation
Molecular Function
- metallocarboxypeptidase activity
- zinc ion binding
Cellular Component
- cellular_component
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000222482
- Coding exons
- 11
- Length
- 31047
- Individuals with no LoFs
- 124887
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 861
- Defined
- 125748
- p
- 0.00343
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.525 | 223 | 246 | 0.906 | 0.0000140 | 2780 |
| Missense (PolyPhen) | 75 | 86.182 | 0.87025 | 1017 | ||
| Synonymous | 0.599 | 96 | 104 | 0.925 | 0.00000688 | 789 |
| Loss of Function | -0.0471 | 26 | 25.7 | 1.01 | 0.00000145 | 268 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0030 | 0.0030 | notable |
| Latino/Admixed American | 0.0019 | 0.0019 | notable |
| Ashkenazi Jewish | 0.0038 | 0.0038 | notable |
| East Asian | 0.0013 | 0.0013 | notable |
| Finnish | 0.0048 | 0.0048 | notable |
| European (Non-Finnish) | 0.0043 | 0.0043 | notable |
| South Asian | 0.0024 | 0.0024 | notable |
| Other | 0.0031 | 0.0031 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Metalloprotease that could be involved in the histone hyperacetylation pathway (PubMed:10383164). Releases a C-terminal amino acid, with preference for -Phe, -Leu, -Ile, -Met, -Tyr and -Val (PubMed:20385563). {ECO:0000269|PubMed:10383164, ECO:0000269|PubMed:20385563}.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.976
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 32.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.748
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |