PON3

paraoxonase 3, the group of Paraoxonases

Basic information

Region (hg38): 7:95359871-95396375

Links

ENSG00000105852 ∙ NCBI:5446 ∙ OMIM:602720 ∙ HGNC:9206 ∙ Uniprot:Q15166 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PON3 gene.

• not provided (28 variants)
• Inborn genetic diseases (15 variants)
• not specified (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 PON3 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				4	3	7
missense			17		5	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding					11	11
Total	0	0	17	4	19

Variants in PON3

This is a list of pathogenic ClinVar variants found in the PON3 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-95359943-C-CT			Benign (Jun 20, 2021)
7-95360006-G-A			Benign (Dec 31, 2019)
7-95360067-C-T			Benign (Dec 31, 2019)
7-95360099-C-G		not specified	Uncertain significance (Jun 22, 2023)
7-95360122-T-A		not specified	Uncertain significance (May 22, 2023)
7-95360125-G-A		not specified	Uncertain significance (Oct 25, 2022)
7-95360136-C-T			Likely benign (Dec 20, 2018)
7-95360361-C-T			Benign (Jun 20, 2021)
7-95362320-T-C			Benign (Jun 20, 2021)
7-95362417-T-A		not specified	Uncertain significance (Jan 10, 2023)
7-95362452-G-A			Likely benign (Dec 27, 2017)
7-95362752-A-G			Benign (Dec 31, 2019)
7-95362764-A-T		not specified	Uncertain significance (Oct 26, 2022)
7-95362797-A-G		not specified	Uncertain significance (Feb 17, 2023)
7-95362932-T-C			Benign (Jun 19, 2021)
7-95363596-G-A			Benign (Jun 19, 2021)
7-95363866-T-C		not specified	Uncertain significance (Feb 10, 2022)
7-95363882-T-C		not specified	Uncertain significance (Dec 20, 2023)
7-95363949-A-G			Benign/Likely benign (Jan 01, 2023)
7-95364002-T-A		not specified	Uncertain significance (Jan 23, 2024)
7-95364022-G-T			Benign (Jun 10, 2021)
7-95364062-C-T		not specified	Uncertain significance (Oct 31, 2018)
7-95367414-G-T		not specified	Uncertain significance (Mar 28, 2022)
7-95367415-T-A		not specified	Uncertain significance (Dec 13, 2023)
7-95367420-C-T			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PON3	protein_coding	protein_coding	ENST00000265627	9	36425

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.10e-7	0.464	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0462	190	188	1.01	0.00000950	2326
Missense in Polyphen		57	62.764	0.90816		820
Synonymous	0.227	68	70.4	0.966	0.00000367	681
Loss of Function	0.804	12	15.4	0.779	6.56e-7	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000218	0.000217
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000230	0.000229
Middle Eastern	0.000218	0.000217
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents. {ECO:0000269|PubMed:15772423}.
• 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: 0.111

Intolerance Scores

• loftool: 0.744
• rvis_EVS: 0.64
• rvis_percentile_EVS: 83.98

Haploinsufficiency Scores

• pHI: 0.108
• hipred: N
• hipred_score: 0.184
• ghis: 0.410

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.917

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pon3
• Phenotype: immune system 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: response to toxic substance;phenylacetate catabolic process;dephosphorylation;lipoxygenase pathway;aromatic compound catabolic process;negative regulation of superoxide anion generation;coumarin catabolic process;carboxylic acid catabolic process
• Cellular component: extracellular region;extracellular space;intracellular membrane-bounded organelle;extracellular exosome
• Molecular function: aryldialkylphosphatase activity;arylesterase activity;3,4-dihydrocoumarin hydrolase activity;protein homodimerization activity;metal ion binding;acyl-L-homoserine-lactone lactonohydrolase activity