PON1

paraoxonase 1, the group of Paraoxonases

Basic information

Region (hg38): 7:95297676-95324532

Previous symbols: [ "PON" ]

Links

ENSG00000005421

∙ NCBI:5444 ∙ OMIM:168820 ∙ HGNC:9204 ∙ Uniprot:P27169 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Clopidogrel treatment, sensitivity to	AD/AR	Pharmacogenomic	Among other associations, variants may be associated with susceptibility to stent thrombosis, possibly related to clopidogrel metabolism, and may thus have pharmacogenomic importance	General	8896566; 11888590; 12454802; 21170047

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PON1 gene.

not_specified (22 variants)
not_provided (9 variants)
PON1-related_disorder (2 variants)
Amyotrophic_lateral_sclerosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PON1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000446.7. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	1 clinvar	4
missense			24 clinvar	4 clinvar	1 clinvar	29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	24	7	2

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PON1	protein_coding	protein_coding	ENST00000222381	9	98686

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.81e-11	0.161	125592	0	156	125748	0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.725	151	178	0.847	0.00000863	2309
Missense in Polyphen		48	62.636	0.76633		818
Synonymous	0.259	67	69.7	0.961	0.00000363	684
Loss of Function	0.578	17	19.8	0.860	0.00000118	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00226	0.00226
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000422	0.000387
Middle Eastern	0.000435	0.000435
South Asian	0.00183	0.00183
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation. {ECO:0000269|PubMed:10479665, ECO:0000269|PubMed:15772423}.;
Disease: DISEASE: Microvascular complications of diabetes 5 (MVCD5) [MIM:612633]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end- stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Homozygosity for the Leu-55 allele is strongly associated with the development of retinal disease in diabetic patients.;
Pathway: Clopidogrel Metabolism Pathway;Clopidogrel Action Pathway;Phase I biotransformations, non P450;Metabolism of lipids;Synthesis of 5-eicosatetraenoic acids;Arachidonic acid metabolism;Metabolism;Fatty acid metabolism (Consensus)

Recessive Scores

pRec: 0.611

Intolerance Scores

loftool: 0.787
rvis_EVS: 0.75
rvis_percentile_EVS: 86.65

Haploinsufficiency Scores

pHI: 0.129
hipred: N
hipred_score: 0.241
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.725

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pon1
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Gene ontology

Biological process: cholesterol metabolic process;response to toxic substance;positive regulation of cholesterol efflux;dephosphorylation;lipoxygenase pathway;aromatic compound catabolic process;response to nutrient levels;positive regulation of transporter activity;negative regulation of plasma lipoprotein oxidation;carboxylic acid catabolic process;organophosphate catabolic process;phosphatidylcholine metabolic process;positive regulation of binding;response to fatty acid;response to fluoride
Cellular component: extracellular region;extracellular space;high-density lipoprotein particle;spherical high-density lipoprotein particle;intracellular membrane-bounded organelle;extracellular exosome;blood microparticle
Molecular function: aryldialkylphosphatase activity;arylesterase activity;calcium ion binding;phospholipid binding;protein homodimerization activity;acyl-L-homoserine-lactone lactonohydrolase activity