PON3

paraoxonase 3, the group of Paraoxonases

Basic information

Region (hg38): 7:95359872-95396375

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 24.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_000940.3	NP_000931.1	9	yes	-
ENST00000265627.10	ENSP00000265627.5	9	yes	-
ENST00000418617.5	ENSP00000393174.1	2	-	-
ENST00000427422.5	ENSP00000413276.1	7	-	-

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_specified (51 variants)
• not_provided (17 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. These statistics are base on transcript: NM_000940.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	1	6
missense			49	2	4	55
nonsense				1		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	49	8	5

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
		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

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

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