PON2: Paraoxonase 2 - Antioxidant and Anti-Inflammatory Gene
Comprehensive genomic and functional analysis of PON2, a member of the paraoxonase gene family with roles in oxidative stress, cardiovascular disease, and cancer.
Gene Information Card
| Symbol | PON2 |
|---|---|
| Full Name | Paraoxonase 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 7q21.3 |
| NCBI Gene ID | 5445 ncbi.nlm.nih.gov/gene/5445 |
| Ensembl ID | ENSG00000105854 |
| UniProt ID | Q15165 |
| OMIM ID | 602447 |
| HGNC ID | 9205 |
| Aliases | PON2, paraoxonase 2, PON2_HUMAN |
Description
PON2 (paraoxonase 2) is a member of the paraoxonase gene family, which also includes PON1 and PON3. It encodes a 354-amino acid protein with lactonase and arylesterase activities. PON2 is ubiquitously expressed, with highest levels in heart, brain, and liver. It functions as an antioxidant enzyme, protecting cells from oxidative stress by hydrolyzing oxidized lipids and preventing low-density lipoprotein (LDL) oxidation. PON2 also exhibits anti-inflammatory properties and is involved in cellular signaling, apoptosis, and detoxification of organophosphates. Genetic variants in PON2 have been associated with cardiovascular disease, type 2 diabetes, and cancer susceptibility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiovascular Disease | PON2 reduces oxidative modification of LDL; loss of function increases atherosclerosis risk. | PMID: 20031578, ClinVar |
| Type 2 Diabetes | PON2 polymorphisms (e.g., C311S) affect insulin sensitivity and oxidative stress. | PMID: 19073726, NCBI |
| Cancer (e.g., breast, prostate) | PON2 overexpression promotes cell survival via antioxidant activity; variants modulate risk. | PMID: 23444367, COSMIC |
| Alzheimer's Disease | PON2 protects against oxidative damage in neurons; reduced activity linked to neurodegeneration. | PMID: 21907147, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 10.2 | Medium |
| Liver | 15.8 | High |
| Kidney | 8.3 | Medium |
| Lung | 6.1 | Low |
| Pancreas | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 14.2 | High expression |
| SH-SY5Y (neuronal) | 11.0 | Moderate expression |
| MCF7 (breast) | 9.5 | Moderate expression |
| A549 (lung) | 5.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.311C>G (p.Cys311Ser) | Missense | 0.25 (global) | Reduced lactonase activity; associated with CAD and diabetes |
| c.148A>G (p.Asn148Asp) | Missense | 0.10 | Altered enzyme stability; possible cancer risk modifier |
| c.584C>T (p.Thr195Ile) | Missense | 0.05 | Decreased antioxidant capacity |
Mutation functional classification
Loss of Function (LOF)
C311S variant reduces lactonase activity and antioxidant protection, increasing oxidative stress.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported.
Dominant Negative (DN)
Not described for PON2.
View complete mutation data：
Gene Ontology (GO)
| • arylesterase activity (GO:0004064) | • hydrolase activity (GO:0016787) |
| • lactonase activity (GO:0016791) | • hemoglobin binding (GO:0030097) |
| • protein binding (GO:0005515) | • lipid metabolic process (GO:0006629) |
| • response to oxidative stress (GO:0006979) | • oxidation-reduction process (GO:0055114) |
Pathways
• REACT: R-HSA-6798695 - Neutrophil degranulation
• REACT: R-HSA-8957275 - Oxidative stress induced senescence
• REACT: R-HSA-2168880 - Metabolism of lipids and lipoproteins
Protein Summary
PON2 is a 40 kDa intracellular protein localized to the endoplasmic reticulum, mitochondria, and plasma membrane. It exhibits lactonase and arylesterase activities, hydrolyzing oxidized phospholipids and homocysteine thiolactone. PON2 protects cells from oxidative stress-induced apoptosis and inflammation. Its expression is regulated by oxidative stress and dietary factors. The C311S polymorphism is the most studied variant, associated with reduced enzyme activity and increased risk for cardiovascular and metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PON2 Knockout HEK293 Cell Line | EDJ-KQ2477 | Human | 5445 | Details Get a Quote |
| PON2 Knockout A-549 Cell Line | EDJ-KQ23046 | Human | 5445 | Details Get a Quote |
| PON2 Knockout HCT 116 Cell Line | EDJ-KQ23047 | Human | 5445 | Details Get a Quote |
| PON2 Knockout HeLa Cell Line | EDJ-KQ23048 | Human | 5445 | Details Get a Quote |
| SPON2 Knockout HEK293 Cell Line | EDJ-KQ50967 | Human | 10417 | Details Get a Quote |
| SPON2 Knockout HeLa Cell Line | EDJ-KQ55404 | Human | 10417 | Details Get a Quote |
| SPON2 Knockout A-549 Cell Line | EDJ-KQ63884 | Human | 10417 | Details Get a Quote |
| SPON2 Knockout HCT 116 Cell Line | EDJ-KQ72342 | Human | 10417 | Details Get a Quote |
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