PLA2G3

protein-coding

phospholipase A2 group III, the group of Phospholipases

Gene summary

This gene encodes a protein that belongs to the secreted phospholipase A2 family, whose members include the bee venom enzyme. The encoded enzyme functions in lipid metabolism and catalyzes the calcium-dependent hydrolysis of the sn-2 acyl bond of phospholipids to release arachidonic acid and lysophospholipids. This enzyme acts as a negative regulator of ciliogenesis, and may play a role in cancer development by stimulating tumor cell growth and angiogenesis. This gene is associated with oxidative stress, and polymorphisms in this gene are linked to risk for Alzheimer's disease. [provided by RefSeq, Apr 2014]

MANE transcript

NM_015715.5

Inheritance

—

ClinVar variants

U:81B:14

Top phenotype

Essential tremor

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr22:31,134,807-31,140,508

External References & Databases

Ensembl (ENSG00000100078)

Transcript & Mutation Effects

hg38 • Region Span ~5.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLA2G3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 1

Essential tremorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015715.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			78 clinvar	13 clinvar		91
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	81	14	0	95

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015715.5	RefSeq	NP_056530.2	7	MANE Select
ENST00000215885.4	Ensembl	ENSP00000215885.3	7	MANE Select
ENST00000927606.1	Ensembl	ENSP00000597665.1	6	Standard
ENST00000927606.2	Ensembl	ENSP00000597665.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ether lipid metabolism - Homo sapiens (human)
Glycerophospholipid metabolism - Homo sapiens (human)
Fat digestion and absorption - Homo sapiens (human)
Vascular smooth muscle contraction - Homo sapiens (human)
alpha-Linolenic acid metabolism - Homo sapiens (human)

Biological Process

acrosome assembly
phospholipid metabolic process
sperm axoneme assembly
lipid catabolic process
lipoxygenase pathway

Molecular Function

phospholipase A2 activity
metal ion binding
calcium-dependent phospholipase A2 activity
phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine)
phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine)

Cellular Component

extracellular region
extracellular space
centriole
plasma membrane
mast cell granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000215885
Coding exons: 7
Length: 5799
Individuals with no LoFs: 124208
Homozygous LoFs: 3
Heterozygous LoFs: 1537
Defined: 125748
p: 0.00614

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0713	307	304	1.01	0.0000176	3258
Missense (PolyPhen)		64	74.826	0.85531		916
Synonymous	-1.16	137	121	1.13	0.00000666	1041
Loss of Function	0.976	19	24.2	0.786	0.00000139	216

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.0086	0.0086	notable
Ashkenazi Jewish	0.027	0.027	notable
East Asian	0.00038	0.00038	rare
Finnish	0.0015	0.0015	notable
European (Non-Finnish)	0.0072	0.0071	notable
South Asian	0.0013	0.0013	notable
Other	0.010	0.010	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: PA2 catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-sn-phosphoglycerides. Shows an 11-fold preference for phosphatidylglycerol over phosphatidylcholine (PC). Preferential cleavage: 1-palmitoyl-2-linoleoyl- phosphatidylethanolamine (PE) > 1-palmitoyl-2-linoleoyl-PC > 1- palmitoyl-2-arachidonoyl-PC > 1-palmitoyl-2-arachidonoyl-PE. Plays a role in ciliogenesis. {ECO:0000269|PubMed:12522102, ECO:0000269|PubMed:20393563}.;

Recessive Scores

pRec: 0.0982

Intolerance Scores

LoFtool: 0.915
RVIS EVS: 1.29
RVIS percentile EVS: 93.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0384

Gene Damage Prediction

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