PON3

Chr 7

paraoxonase 3

NCBI Gene: 5446ENSG00000105852UniProt: Q15166

This gene is a member of the paraoxonase family and lies in a cluster on chromosome 7 with the other two family members. The encoded protein is secreted into the bloodstream and associates with high-density lipoprotein (HDL). The protein also rapidly hydrolyzes lactones and can inhibit the oxidation of low-density lipoprotein (LDL), a function that is believed to slow the initiation and progression of atherosclerosis. Alternatively spliced variants which encode different protein isoforms have been described; however, only one has been fully characterized. [provided by RefSeq, Jul 2008]

96
ClinVar variants
17
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PON3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 51 VUS of 96 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.
1.26LOEUF
pLI 0.000
Z-score 0.80
OE 0.78 (0.50–1.26)
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.
-0.05Z-score
OE missense 1.01 (0.90–1.14)
190 obs / 188.2 exp
Tolerant

Tolerant to missense variation

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.0.78 (0.50–1.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.90–1.14)
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.0.97
0≤1.21.6
LoF obs/exp: 12 / 15.4Missense obs/exp: 190 / 188.2Syn Z: 0.23

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
VUS51
Likely Benign8
Benign19
Conflicting1
17
Pathogenic
51
VUS
8
Likely Benign
19
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
0
0
0
VUS
0
49
2
0
51
Likely Benign
0
2
1
5
8
Benign
0
4
12
3
19
Conflicting
—1
Total05532896

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

View in ClinVar →

Protein Context — Lollipop Plot

PON3 · 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
PARAOXONASE 3; PON3
MIM #602720 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metals and Paraoxonases.
Costa LG et al.·Adv Neurobiol
2017Review
Paraoxonases and infectious diseases.
Camps J et al.·Clin Biochem
2017Review
Paraoxonase genes and disease.
Hegele RA·Ann Med
1999Review
PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.
Zhu L et al.·Am J Surg Pathol
2024
Omics data integration analysis identified new biological insights into chronic antibody-mediated rejection (CAMR).
Bruschi M et al.·J Transl Med
2025
Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities.
Draganov DI et al.·J Lipid Res
2005
Regulation of Human Hydrolases and Its Implications in Pharmacokinetics and Pharmacodynamics.
Jung SM et al.·Drug Metab Dispos
2024Review
The human paraoxonase gene cluster as a target in the treatment of atherosclerosis.
She ZG et al.·Antioxid Redox Signal
2012Review
Protective effects of transgene expressed human PON3 against CCl4-induced subacute liver injury in mice.
Peng W et al.·Biomed Pharmacother
2009
Paraoxonase 3: Structure and Its Role in Pathophysiology of Coronary Artery Disease.
Priyanka K et al.·Biomolecules
2019Review
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