CPA1 Gene - Carboxypeptidase A1
A key pancreatic digestive enzyme gene linked to chronic pancreatitis and cancer susceptibility
Gene Information Card
| Symbol | CPA1 |
|---|---|
| Full Name | Carboxypeptidase A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q32.2 |
| NCBI Gene ID | 1357 ncbi.nlm.nih.gov/gene/1357 |
| Ensembl ID | ENSG00000191721 |
| UniProt ID | P15085 |
| OMIM ID | 114850 |
| HGNC ID | 2296 |
| Aliases | CPA |
Description
The CPA1 gene encodes carboxypeptidase A1, a pancreatic exopeptidase that hydrolyzes C-terminal aromatic or aliphatic amino acids from dietary proteins. It is synthesized as an inactive zymogen (procarboxypeptidase A1) and activated by trypsin in the small intestine. CPA1 is critical for protein digestion and is predominantly expressed in the pancreas. Mutations in CPA1 are associated with chronic pancreatitis and have been implicated in pancreatic cancer susceptibility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic pancreatitis | Missense mutations (e.g., p.N256K, p.R272C) cause misfolding and ER stress, leading to acinar cell damage | PMID: 23683987, ClinVar |
| Pancreatic cancer | Somatic mutations and altered expression may contribute to tumorigenesis; CPA1 is a candidate susceptibility gene | COSMIC, PMID: 26030186 |
| Carboxypeptidase A deficiency | Rare loss-of-function variants impair digestive enzyme activity | OMIM #114850 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 1123.2 | High |
| Duodenum | 12.1 | Low |
| Small intestine | 8.5 | Low |
| Stomach | 1.2 | Not detected |
| Liver | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| PANC-1 (pancreatic cancer) | 45.2 | Moderate expression |
| MIA PaCa-2 (pancreatic cancer) | 38.7 | Moderate expression |
| BxPC-3 (pancreatic cancer) | 52.1 | Moderate expression |
| HeLa (cervical cancer) | 0.5 | Not detected |
| HEK293 (embryonic kidney) | 0.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.N256K | Missense | Rare (0.1% in general population) | Loss of function; misfolding, ER stress, chronic pancreatitis risk |
| p.R272C | Missense | Rare (0.05%) | Loss of function; impaired secretion, chronic pancreatitis |
| p.Y185X | Nonsense | Very rare | Truncated protein; loss of enzymatic activity |
| c.77+1G>A | Splice site | Rare | Splicing defect; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.N256K, p.R272C) cause misfolding, ER retention, and reduced enzymatic activity, leading to chronic pancreatitis.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported for CPA1.
Dominant Negative (DN)
Some CPA1 mutants may exert dominant-negative effects by interfering with wild-type protein folding or secretion, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • metallocarboxypeptidase activity (GO:0004181) | • proteolysis (GO:0006508) |
| • extracellular space (GO:0005615) | • secretory granule (GO:0030141) |
| • zinc ion binding (GO:0008270) |
Pathways
• Digestion and absorption of proteins (Reactome: R-HSA-8963743)
• Pancreatic secretion (KEGG: hsa04972)
Protein Summary
Carboxypeptidase A1 (UniProt P15085) is a 419-amino-acid zinc-dependent metalloprotease synthesized as a preproprotein. After signal peptide cleavage, the proenzyme (procarboxypeptidase A1) is activated by trypsin to yield the mature enzyme. It preferentially cleaves C-terminal aromatic (Phe, Tyr, Trp) and aliphatic (Leu, Ile, Met) residues. The protein is highly expressed in pancreatic acinar cells and stored in zymogen granules. Structural analysis reveals a classic carboxypeptidase fold with a catalytic zinc ion coordinated by His69, Glu72, and His196. Mutations affecting folding or catalytic activity are linked to pancreatic pathology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CPA1 Knockout HEK293 Cell Line | EDJ-KQ4332 | Human | 1357 | Details Get a Quote |
| CPA1 Knockout HeLa Cell Line | EDJ-KQ52966 | Human | 1357 | Details Get a Quote |
| CPA1 Knockout A-549 Cell Line | EDJ-KQ61434 | Human | 1357 | Details Get a Quote |
| CPA1 Knockout HCT 116 Cell Line | EDJ-KQ69930 | Human | 1357 | Details Get a Quote |
