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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CPA4
carboxypeptidase A4
Chromosome 7 · 7q32.2
NCBI Gene: 51200Ensembl: ENSG00000128510.12HGNC: HGNC:15740UniProt: A4D1M3
41PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
metallocarboxypeptidase activityhormone catabolic processpeptide catabolic processGO:0005615rheumatoid arthritisnon-small cell lung carcinomalung cancerbreast cancer
✦AI Summary

CPA4 (carboxypeptidase A4) is a zinc-containing metallocarboxypeptidase that cleaves hydrophobic C-terminal amino acid residues, with demonstrated preference for phenylalanine, leucine, isoleucine, methionine, tyrosine, and valine 1. The enzyme is proposed to function in peptide hormone and neuropeptide catabolism 1. However, emerging evidence reveals CPA4's significant role in cancer biology, where it is consistently overexpressed across multiple malignancies including clear cell renal cell carcinoma, non-small-cell lung cancer, anaplastic thyroid cancer, endometrial cancer, hepatocellular carcinoma, and breast cancer 234567. CPA4 promotes cancer cell proliferation, migration, invasion, and stem cell characteristics through activation of key signaling pathways including PI3K-AKT-mTOR 86. In thyroid cancer, CPA4 mediates crosstalk between M2 macrophages and cancer cells, creating a positive feedback loop that enhances tumor progression 4. Additionally, CPA4 promotes cardiac hypertrophy by activating PI3K-AKT-mTOR signaling in cardiomyocytes 8. High CPA4 expression correlates with poor prognosis across multiple cancer types, making it a potential diagnostic biomarker and therapeutic target 325.

Sources cited
1
CPA4 cleaves hydrophobic C-terminal residues and may function in peptide hormone/neuropeptide catabolism
PMID: 20385563
2
CPA4 overexpression in clear cell renal cell carcinoma promotes proliferation, migration and metastasis
PMID: 38494845
3
CPA4 is overexpressed in non-small-cell lung cancer and correlates with poor prognosis
PMID: 27390594
4
CPA4 mediates crosstalk between M2 macrophages and anaplastic thyroid cancer cells
PMID: 38666696
5
CPA4 overexpression correlates with poor prognosis in endometrial cancer
PMID: 40089797
6
CPA4 promotes hepatocellular carcinoma proliferation and stem cell characteristics
PMID: 31058377
7
CPA4 promotes cardiac hypertrophy through PI3K-AKT-mTOR signaling activation
PMID: 32347291
8
CPA4 has diagnostic and prognostic significance in breast cancer
PMID: 30875843
Disease Associationsⓘ20
rheumatoid arthritisOpen Targets
0.19Weak
non-small cell lung carcinomaOpen Targets
0.10Suggestive
lung cancerOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
endometrial cancerOpen Targets
0.08Suggestive
liver cancerOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
bladder transitional cell carcinomaOpen Targets
0.08Suggestive
pachyonychia congenitaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
cancerOpen Targets
0.06Suggestive
colorectal cancerOpen Targets
0.05Suggestive
myxosarcomaOpen Targets
0.04Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.04Suggestive
Abnormality of the skeletal systemOpen Targets
0.04Suggestive
esophageal adenocarcinomaOpen Targets
0.04Suggestive
prostate cancerOpen Targets
0.04Suggestive
gliomaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LXNProtein interaction100%CMA1Protein interaction85%TPSAB1Protein interaction75%MESTProtein interaction72%CTSGProtein interaction72%LVRNShared pathway67%
Tissue Expression6 tissues
Brain
100%
Heart
89%
Liver
57%
Ovary
43%
Lung
43%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CPA4LXNCMA1TPSAB1MESTCTSGLVRN
PROTEIN STRUCTURE
Preparing viewer…
PDB2BO9 · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.09LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.79 [0.58–1.09]
RankingsWhere CPA4 stands among ~20K protein-coding genes
  • #9,987of 20,598
    Most Researched41
  • #11,154of 17,882
    Most Constrained (LOEUF)1.09
Genes detectedCPA4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CPA4 as a biomarker promotes the proliferation, migration and metastasis of clear cell renal cell carcinoma cells.
PMID: 38494845
J Cell Mol Med · 2024
1.00
2
CPA4 is a Novel Diagnostic and Prognostic Marker for Human Non-Small-Cell Lung Cancer.
PMID: 27390594
J Cancer · 2016
0.90
3
Macrophage-Induced Carboxypeptidase A4 Promotes the Progression of Anaplastic Thyroid Cancer.
PMID: 38666696
Thyroid · 2024
0.80
4
CPA4 overexpression correlates with poor prognosis and tumor progression in endometrial cancer.
PMID: 40089797
Eur J Med Res · 2025
0.70
5
Carboxypeptidase A4 promotes proliferation and stem cell characteristics of hepatocellular carcinoma.
PMID: 31058377
Int J Exp Pathol · 2019
0.60