CPA1

Chr 7

carboxypeptidase A1

Also known as: CPA

NCBI Gene: 1357ENSG00000091704UniProt: P15085

This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. This enzyme is produced in the pancreas and preferentially cleaves C-terminal branched-chain and aromatic amino acids from dietary proteins. This gene and several family members are present in a gene cluster on chromosome 7. Mutations in this gene may be linked to chronic pancreatitis, while elevated protein levels may be associated with pancreatic cancer. [provided by RefSeq, Jan 2015]

599
ClinVar variants
2
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CPA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2 Pathogenic / Likely Pathogenic· 383 VUS of 599 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.27LOEUF
pLI 0.000
Z-score 0.60
OE 0.86 (0.59–1.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.04Z-score
OE missense 0.82 (0.73–0.92)
209 obs / 255.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.86 (0.59–1.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.73–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 18 / 21.0Missense obs/exp: 209 / 255.6Syn Z: 1.08

ClinVar Variant Classifications

599 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
VUS383
Likely Benign205
Conflicting9
2
Pathogenic
383
VUS
205
Likely Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
0
0
0
VUS
7
360
15
1
383
Likely Benign
6
16
22
161
205
Benign
0
0
0
0
0
Conflicting
—9
Total1337639162599

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CPA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — CPA1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prevalence of Germline Sequence Variations Among Patients With Pancreatic Cancer in China.
Yin L et al.·JAMA Netw Open
2022Cohort
Comparing virtual reality and balance training effects on postural strategies during ball kicking in soccer players with chronic ankle instability.
Faghihi R et al.·Sci Rep
2024
Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis.
Kawamoto M et al.·Int J Cancer
2022Meta-analysis
CPA1 (S282P) mutation leads to chronic pancreatitis in rabbits.
Yang J et al.·Zool Res
2025
Germline multigene panel testing in acute and chronic pancreatitis.
Ramsey ML et al.·PLoS One
2024
Novel p.G250A Mutation Associated with Chronic Pancreatitis Highlights Misfolding-Prone Region in Carboxypeptidase A1 (CPA1).
Sándor M et al.·Int J Mol Sci
2022
Spectrum of PRSS1, SPINK1, CTRC, CFTR, and CPA1 Gene Variants in Chronic Pancreatitis Patients in Russia.
Litvinova MM et al.·Sovrem Tekhnologii Med
2023Cohort
Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer.
Tamura K et al.·Proc Natl Acad Sci U S A
2018Clinical trial
The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children.
Abu-El-Haija M et al.·Clin Gastroenterol Hepatol
2024
Scale and Scope of Gene-Alcohol Interactions in Chronic Pancreatitis: A Systematic Review.
Chen JM et al.·Genes (Basel)
2021Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools