PON2

protein-coding

paraoxonase 2, the group of Paraoxonases

Gene summary

This gene encodes a member of the paraoxonase gene family, which includes three known members located adjacent to each other on the long arm of chromosome 7. The encoded protein is ubiquitously expressed in human tissues, membrane-bound, and may act as a cellular antioxidant, protecting cells from oxidative stress. Hydrolytic activity against acylhomoserine lactones, important bacterial quorum-sensing mediators, suggests the encoded protein may also play a role in defense responses to pathogenic bacteria. Mutations in this gene may be associated with vascular disease and a number of quantitative phenotypes related to diabetes. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000305.3

Inheritance

—

ClinVar variants

U:51B:23

Top phenotype

PON2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr7:95,404,862-95,435,329

External References & Databases

Ensembl (ENSG00000105854)

Transcript & Mutation Effects

hg38 • Region Span ~30.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PON2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 8

PON2-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000305.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				10 clinvar	5 clinvar	15
missense			47 clinvar	7 clinvar	1 clinvar	55
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	51	17	6	74

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000305.3	RefSeq	NP_000296.2	9	MANE Select
ENST00000222572.8	Ensembl	ENSP00000222572.3	9	MANE Select
NM_001018161.2	RefSeq	NP_001018171.1	9	Standard
ENST00000433091.6	Ensembl	ENSP00000404622.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phase I biotransformations, non P450
Metabolism of lipids
Synthesis of 5-eicosatetraenoic acids
Arachidonic acid metabolism
Metabolism

Biological Process

response to oxidative stress
response to toxic substance
lipoxygenase pathway
aromatic compound catabolic process

Molecular Function

arylesterase activity
identical protein binding
metal ion binding
acyl-L-homoserine-lactone lactonohydrolase activity

Cellular Component

extracellular region
nucleus
mitochondrion
lysosome
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000222572
Coding exons: 9
Length: 30336
Individuals with no LoFs: 125428
Homozygous LoFs: 2
Heterozygous LoFs: 318
Defined: 125748
p: 0.00127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.755	154	183	0.843	0.00000893	2306
Missense (PolyPhen)		31	36.806	0.84225		465
Synonymous	-0.343	73	69.4	1.05	0.00000342	697
Loss of Function	1.49	9	15.3	0.589	7.09e-7	207

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.0013	0.0012	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00065	0.00065	rare
European (Non-Finnish)	0.0020	0.0019	notable
South Asian	0.00082	0.00082	rare
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Capable of hydrolyzing lactones and a number of aromatic carboxylic acid esters. Has antioxidant activity. Is not associated with high density lipoprotein. Prevents LDL lipid peroxidation, reverses the oxidation of mildly oxidized LDL, and inhibits the ability of MM-LDL to induce monocyte chemotaxis. {ECO:0000269|PubMed:11579088, ECO:0000269|PubMed:15772423}.;

Recessive Scores

pRec: 0.516

Intolerance Scores

LoFtool: 0.823
RVIS EVS: 0.4
RVIS percentile EVS: 76.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High