PON2

paraoxonase 2, the group of Paraoxonases

Basic information

Region (hg38): 7:95404861-95435329

Links

ENSG00000105854 ∙ NCBI:5445 ∙ OMIM:602447 ∙ HGNC:9205 ∙ Uniprot:Q15165 ∙ 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 PON2 gene.

• not specified (22 variants)
• not provided (21 variants)
• Inborn genetic diseases (9 variants)
• PARAOXONASE 2 POLYMORPHISM (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PON2 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				8	2	10
missense			14	4	4	22
nonsense						0
start loss						0
frameshift			2			2
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region			2			2
non coding			1	1	11	13
Total	0	0	17	14	17

Variants in PON2

This is a list of pathogenic ClinVar variants found in the PON2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-95405326-C-T		not specified	Uncertain significance (Aug 01, 2023)
7-95405463-G-C		PARAOXONASE 2 POLYMORPHISM	Benign (Jun 09, 2021)
7-95405509-A-T			Benign (Jun 20, 2021)
7-95406125-C-T		not specified	Likely benign (Sep 25, 2021)
7-95406140-C-T			Likely benign (Mar 13, 2017)
7-95406141-G-A			Uncertain significance (-)
7-95406152-G-A		not specified	Likely benign (Aug 01, 2023)
7-95406193-C-T		not specified	Uncertain significance (Jan 24, 2023)
7-95406270-A-T			Benign (Jun 19, 2021)
7-95406821-A-T			Benign (Jun 19, 2021)
7-95407039-T-C		not specified	Uncertain significance (Apr 05, 2023)
7-95407056-A-C		not specified	Benign/Likely benign (Nov 20, 2023)
7-95407066-T-C		not specified	Uncertain significance (Nov 27, 2023)
7-95409887-A-G		not specified	Benign (Feb 03, 2020)
7-95409894-G-A		not specified	Uncertain significance (May 18, 2023)
7-95409919-T-C		not specified	Likely benign (Jun 15, 2020)
7-95409936-A-G		not specified	Likely benign (Aug 06, 2023)
7-95409980-AAAC-A		not specified	Likely benign (Apr 02, 2019)
7-95410026-T-G		not specified	Uncertain significance (Jan 05, 2022)
7-95410082-C-G			Benign (Dec 31, 2019)
7-95410133-C-T			Benign (Jun 19, 2021)
7-95411676-T-C			Likely benign (Nov 01, 2017)
7-95411684-G-A		PON2-related disorder	Likely benign (Sep 19, 2019)
7-95411691-C-T		not specified	Benign (Jul 10, 2022)
7-95411704-G-C		PARAOXONASE 2 POLYMORPHISM	Benign (Jun 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PON2	protein_coding	protein_coding	ENST00000222572	9	30336

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000544	0.891	125428	2	318	125748	0.00127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.755	154	183	0.843	0.00000893	2306
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00170	0.00170
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000647	0.000647
European (Non-Finnish)	0.00195	0.00194
Middle Eastern	0.0000544	0.0000544
South Asian	0.000819	0.000817
Other	0.00147	0.00147

dbNSFP

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}.
• 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: 0.516

Intolerance Scores

• loftool: 0.823
• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.15

Haploinsufficiency Scores

• pHI: 0.132
• hipred: N
• hipred_score: 0.248
• ghis: 0.462

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pon2
• Phenotype: immune system phenotype; hematopoietic 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); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: response to oxidative stress;response to toxic substance;lipoxygenase pathway;aromatic compound catabolic process
• Cellular component: extracellular region;nucleus;mitochondrion;lysosome;plasma membrane
• Molecular function: arylesterase activity;identical protein binding;metal ion binding;acyl-L-homoserine-lactone lactonohydrolase activity