PLA2G2A

protein-coding

phospholipase A2 group IIA, the group of Phospholipases

Gene summary

The protein encoded by this gene is a member of the phospholipase A2 family (PLA2). PLA2s constitute a diverse family of enzymes with respect to sequence, function, localization, and divalent cation requirements. This gene product belongs to group II, which contains secreted form of PLA2, an extracellular enzyme that has a low molecular mass and requires calcium ions for catalysis. It catalyzes the hydrolysis of the sn-2 fatty acid acyl ester bond of phosphoglycerides, releasing free fatty acids and lysophospholipids, and thought to participate in the regulation of the phospholipid metabolism in biomembranes. Several alternatively spliced transcript variants with different 5' UTRs have been found for this gene.[provided by RefSeq, Sep 2009]

Previous symbols:

PLA2B
PLA2L

MANE transcript

NM_001395463.1

Inheritance

ClinVar variants

P:1U:24B:6

Top phenotype

PLA2G2A-related disorder

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr1:19,975,431-19,980,416

External References & Databases

Ensembl (ENSG00000188257)

Transcript & Mutation Effects

hg38 • Region Span ~5.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

colorectal cancerNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0005575

Submitter: Labcorp Genetics (formerly Invitae)

colorectal cancerLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005575

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLA2G2A variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 24

PLA2G2A-related disorderTotal: 3

not providedTotal: 3

Familial colorectal cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001395463.1. 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			23 clinvar	2 clinvar	2 clinvar	27
nonsense						0
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	1	0	24	3	3	31

Highest pathogenic variant AF is 0.00003780648

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001395463.1	RefSeq	NP_001382392.1	4	MANE Select
ENST00000482011.3	Ensembl	ENSP00000504762.1	4	MANE Select
NM_000300.4	RefSeq	NP_000291.1	4	Standard
NM_001161727.2	RefSeq	NP_001155199.1	4	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

phospholipid metabolic process
phosphatidic acid biosynthetic process
positive regulation of macrophage derived foam cell differentiation
lipid catabolic process
antimicrobial humoral response

Molecular Function

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

Cellular Component

extracellular region
extracellular space
endoplasmic reticulum
endoplasmic reticulum membrane
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375111
Coding exons: 4
Length: 5008
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.684	64	81.4	0.787	0.00000480	945
Missense (PolyPhen)		16	31.237	0.51221		371
Synonymous	-0.563	36	32.0	1.13	0.00000188	259
Loss of Function	1.18	2	4.80	0.417	2.03e-7	66

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides (PubMed:2925633). Thought to participate in the regulation of phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Independent of its catalytic activity, acts as a ligand for integrins (PubMed:18635536, PubMed:25398877). Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 (PubMed:18635536, PubMed:25398877). Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:25398877). Induces cell proliferation in an integrin-dependent manner (PubMed:18635536). {ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:2925633}.;

Recessive Scores

pRec: 0.195

Intolerance Scores

LoFtool: 0.829
RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.971

Gene Damage Prediction

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