PON1

paraoxonase 1, the group of Paraoxonases

Basic information

Region (hg38): 7:95297675-95324532

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 provided (36 variants)
• Inborn genetic diseases (5 variants)
• Coronary artery disease, susceptibility to (2 variants)
• Enzyme activity finding (2 variants)
• Microvascular complications of diabetes, susceptibility to, 5 (1 variants)
• Coronary artery spasm 2, susceptibility to (1 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			7	2	3	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					26	26
Total	0	0	7	3	30

Variants in PON1

This is a list of pathogenic ClinVar variants found in the PON1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-95299242-AAC-A			Benign (Jun 20, 2021)
7-95301923-T-TA			Benign (Jun 19, 2021)
7-95301923-T-TAA			Benign (Jun 20, 2021)
7-95301959-T-C			Benign (Jun 20, 2021)
7-95302075-C-T			Benign (Jun 21, 2021)
7-95302113-AAAAAAAAAC-A			Benign (Jun 20, 2021)
7-95302248-A-T			Uncertain significance (Jun 04, 2021)
7-95302288-C-T		not specified	Uncertain significance (Jun 29, 2022)
7-95302317-G-T		not specified	Uncertain significance (Nov 08, 2021)
7-95302632-G-GA			Benign (Jun 20, 2021)
7-95306277-C-T			Likely benign (Aug 16, 2018)
7-95306337-T-G		not specified	Uncertain significance (Sep 22, 2023)
7-95306352-G-T		not specified	Uncertain significance (Aug 23, 2021)
7-95306358-T-C		Amyotrophic lateral sclerosis	Uncertain significance (Mar 31, 2020)
7-95306593-A-G			Benign (Jun 20, 2021)
7-95308100-C-T		PON1-related disorder	Likely benign (Mar 18, 2019)
7-95308106-C-T			Benign (Aug 08, 2018)
7-95308134-T-C		Coronary artery disease, susceptibility to • Coronary artery spasm 2, susceptibility to • Enzyme activity finding • PON1-related disorder	Benign (Oct 18, 2019)
7-95308156-A-T		not specified	Uncertain significance (Jan 03, 2024)
7-95308312-G-A			Benign (Jun 20, 2021)
7-95308384-T-TAA			Benign (Jun 19, 2021)
7-95308475-CGT-C			Benign (Jun 20, 2021)
7-95308475-CGTGT-C			Benign (Jun 19, 2021)
7-95308475-CGTGTGT-C			Benign (Jun 19, 2021)
7-95308475-CGTGTGTGT-C			Benign (Jun 19, 2021)

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

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