PON1: Paraoxonase 1 - A Key Player in Organophosphate Detoxification and Cardiovascular Protection
Comprehensive genomic and proteomic analysis of PON1, including its role in oxidative stress, lipid metabolism, and disease association.
Gene Information Card
| Symbol | PON1 |
|---|---|
| Full Name | Paraoxonase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.3 |
| NCBI Gene ID | 5444 ncbi.nlm.nih.gov/gene/5444 |
| Ensembl ID | ENSG00000005421 |
| UniProt ID | P27169 |
| OMIM ID | 168820 |
| HGNC ID | 9204 |
| Aliases | ESA, PON, PONase, A-esterase, arylesterase, serum aryldialkylphosphatase |
Description
PON1 (paraoxonase 1) encodes a member of the paraoxonase family of calcium-dependent hydrolases. The encoded enzyme is primarily synthesized in the liver and secreted into the blood, where it associates with high-density lipoprotein (HDL). PON1 hydrolyzes organophosphate insecticides (e.g., paraoxon), nerve agents, and aromatic esters, and also exhibits lactonase activity. It protects against oxidative modification of low-density lipoproteins (LDL) and plays a role in cardiovascular disease, diabetes, and Alzheimer's disease. Common coding polymorphisms (Q192R, L55M) influence enzyme activity and substrate specificity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Coronary Artery Disease | Reduced PON1 activity leads to increased oxidative stress and LDL oxidation, promoting atherosclerosis. | Multiple case-control studies; meta-analyses show association between PON1 Q192R and CAD risk. |
| Organophosphate Poisoning | PON1 hydrolyzes organophosphates; low activity variants increase susceptibility to toxicity. | Epidemiological studies and in vitro assays; ClinVar records. |
| Type 2 Diabetes | Oxidative stress and altered HDL function; PON1 polymorphisms affect diabetes risk. | Association studies; OMIM #168820. |
| Alzheimer's Disease | Oxidative damage and lipid peroxidation; PON1 may modulate amyloid-beta toxicity. | Case-control studies; limited evidence. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 48.2 | High |
| Kidney | 12.1 | Medium |
| Lung | 5.3 | Low |
| Colon | 3.8 | Low |
| Blood (whole blood) | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 62.5 | High expression; primary site of synthesis |
| HEK293 (embryonic kidney) | 8.4 | Moderate expression |
| A549 (lung) | 2.1 | Low expression |
| K562 (leukemia) | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Q192R (rs662) | Missense | ~30-40% (global) | Alters substrate specificity: R192 hydrolyzes paraoxon faster, Q192 hydrolyzes diazoxon and soman faster. |
| L55M (rs854560) | Missense | ~10-20% (global) | Affects protein stability and activity; M55 associated with lower PON1 levels. |
| C-108T (rs705379) | Promoter | ~40-50% (global) | Reduces transcription; associated with lower PON1 expression. |
Mutation functional classification
Loss of Function (LOF)
L55M (rs854560) reduces enzyme stability and serum PON1 activity; promoter variant C-108T decreases transcription.
Gain of Function (GOF)
Q192R (rs662) increases hydrolysis of paraoxon but decreases hydrolysis of other substrates (e.g., diazoxon).
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for PON1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Organophosphate detoxification (Reactome: R-HSA-2161522)
• HDL-mediated lipid transport and metabolism (Reactome: R-HSA-174824)
• Oxidative stress response (KEGG: hsa05016)
Protein Summary
Paraoxonase 1 (PON1) is a 354-amino acid, 43 kDa calcium-dependent hydrolase synthesized in the liver and secreted into plasma, where it binds to HDL. The enzyme possesses arylesterase, lactonase, and organophosphatase activities. It protects LDL and HDL from oxidative modification by hydrolyzing lipid peroxides. PON1 activity varies widely among individuals due to common polymorphisms (Q192R, L55M) and environmental factors. Reduced PON1 activity is associated with increased risk of cardiovascular disease, diabetes, and susceptibility to organophosphate toxicity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PON1 Knockout HEK293 Cell Line | EDJ-KQ513 | Human | 5444 | Details Get a Quote |
| SPON1 Knockout HEK293 Cell Line | EDJ-KQ7039 | Human | 10418 | Details Get a Quote |
| PON1 Knockout A-549 Cell Line | EDJ-KQ20184 | Human | 5444 | Details Get a Quote |
| PON1 Knockout HeLa Cell Line | EDJ-KQ54174 | Human | 5444 | Details Get a Quote |
| SPON1 Knockout HeLa Cell Line | EDJ-KQ55405 | Human | 10418 | Details Get a Quote |
| SPON1 Knockout A-549 Cell Line | EDJ-KQ63885 | Human | 10418 | Details Get a Quote |
| PON1 Knockout HCT 116 Cell Line | EDJ-KQ71138 | Human | 5444 | Details Get a Quote |
| SPON1 Knockout HCT 116 Cell Line | EDJ-KQ72343 | Human | 10418 | Details Get a Quote |
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