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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CPN2
carboxypeptidase N subunit 2
Chromosome 3 · 3q29
NCBI Gene: 1370Ensembl: ENSG00000178772.8HGNC: HGNC:2313UniProt: P22792
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomeblood microparticlesignaling receptor activityplasma membranemuscle crampAtypical behaviorglioblastoma multiformelung adenocarcinoma
✦AI Summary

CPN2 (carboxypeptidase N subunit 2) is an 83 kDa regulatory subunit that stabilizes and maintains circulating carboxypeptidase N (CPN), a plasma zinc metalloprotease 1. CPN2 protects the catalytic subunit (CPN1) from degradation at physiological temperature and may function as an allosteric modulator. The CPN complex cleaves C-terminal arginines and lysines from inflammatory mediators including complement anaphylatoxins and kinins, thereby modulating their biological activity 1. CPN2 exhibits immunoregulatory function by suppressing NF-κB pathway activation and reducing inflammatory cytokine production 2. In cryptorchidism models, CPN2 overexpression preserved spermatogonial stem cell proliferation and reduced apoptosis by inhibiting plasma cell infiltration 2. Genetic studies identified CPN2 as a causal factor influencing myasthenia gravis susceptibility through protein quantitative trait loci (pQTL) mechanisms 3. CPN2 serves as a disease biomarker across multiple conditions. Altered CPN2 expression appears in hepatocellular carcinoma serum extracellular vesicles 4, type 1 diabetes 5, and canine chr3 inflammatory enteropathies where CPN2 downregulation correlates with disease remission 6. Additionally, CPN2 shows differential regulation in protein S deficiency-associated coagulopathy 7 and Sézary syndrome through novel fusion transcripts 8. These findings establish CPN2 as a pleiotropic regulator of inflammation and immune responses with diagnostic and therapeutic potential.

Sources cited
1
CPN2 is the large regulatory subunit that protects catalytic CPN1 from degradation; CPN cleaves C-terminal arginines and lysines from inflammatory peptides
PMID: 14687935
2
CPN2 suppresses NF-κB activation and plasma cell infiltration, preserves spermatogonial stem cell proliferation, and reduces inflammatory cytokines in cryptorchidism
PMID: 40720213
3
CPN2 identified as causal protein through pQTL genetic instruments influencing myasthenia gravis susceptibility
PMID: 38521921
4
CPN2 identified as vesicular protein biomarker signature for distinguishing hepatocellular carcinoma in extracellular vesicles
PMID: 39207047
5
CPN2 expression levels altered in serum of type 1 diabetes patients compared to healthy controls
PMID: 36115450
6
CPN2 downregulated during remission in canine chronic inflammatory enteropathies, associated with DNA remodeling and methylation pathways
PMID: 40659816
7
CPN2 identified as differential protein correlated with protein S in familial protein S deficiency coagulopathy
PMID: 39265992
8
CPN2 involved in novel fusion transcript (PTPRC-CPN2) in Sézary syndrome with ectopic gene expression
PMID: 28489605
Disease Associationsⓘ20
muscle crampOpen Targets
0.29Weak
Atypical behaviorOpen Targets
0.29Weak
glioblastoma multiformeOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.07Suggestive
aortic stenosisOpen Targets
0.06Suggestive
lung cancerOpen Targets
0.06Suggestive
decubitus ulcerOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.04Suggestive
gram-negative bacterial infectionsOpen Targets
0.04Suggestive
gastric cancerOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
obesityOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
non-alcoholic steatohepatitisOpen Targets
0.03Suggestive
type 1 diabetes mellitusOpen Targets
0.02Suggestive
breast carcinomaOpen Targets
0.02Suggestive
Mungan syndromeOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
clear cell renal carcinomaOpen Targets
0.02Suggestive
urethral syndromeOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ASDURFShared pathway100%PYURFShared pathway100%HAPSTR2Shared pathway100%PAQR4Shared pathway100%NAA30Shared pathway100%TTI2Shared pathway100%
Tissue Expression6 tissues
Liver
100%
Heart
0%
Brain
0%
Lung
0%
Ovary
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CPN2ASDURFPYURFHAPSTR2PAQR4NAA30TTI2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P22792
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.83LoF Tolerant
pLIⓘ
0.20Tolerant
Observed/Expected LoF0.66 [0.21–1.83]
RankingsWhere CPN2 stands among ~20K protein-coding genes
  • #14,391of 20,598
    Most Researched19
  • #16,722of 17,882
    Most Constrained (LOEUF)1.83
Genes detectedCPN2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The trajectory of vesicular proteomic signatures from HBV-HCC by chitosan-magnetic bead-based separation and DIA-proteomic analysis.
PMID: 39207047
J Extracell Vesicles · 2024
1.00
2
CPN2 alleviates cryptorchidism by inhibiting the NF-κB pathway and regulating immune responses.
PMID: 40720213
Autoimmunity · 2025
0.90
3
Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis.
PMID: 38521921
J Transl Med · 2024
0.80
4
UPLC-HDMS
PMID: 36115450
Int J Biol Macromol · 2022
0.70
5
Carboxypeptidase N: a pleiotropic regulator of inflammation.
PMID: 14687935
Mol Immunol · 2004
0.60