PLA2G3

Chr 22

phospholipase A2 group III

Also known as: GIII-SPLA2, SPLA2III, sPLA2-III

NCBI Gene: 50487ENSG00000100078UniProt: Q9NZ20

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]

119
ClinVar variants
18
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PLA2G3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 79 VUS of 119 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.15LOEUF
pLI 0.000
Z-score 0.98
OE 0.79 (0.55–1.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.07Z-score
OE missense 1.01 (0.92–1.11)
307 obs / 303.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.79 (0.55–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.92–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 19 / 24.2Missense obs/exp: 307 / 303.5Syn Z: -1.16

ClinVar Variant Classifications

119 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic1
VUS79
Likely Benign14
17
Pathogenic
1
Likely Pathogenic
79
VUS
14
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
1
0
1
VUS
1
77
1
0
79
Likely Benign
0
13
0
1
14
Benign
0
0
0
0
0
Total190191111

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PLA2G3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Group III phospholipase A2 downregulation attenuated survival and metastasis in ovarian cancer and promotes chemo-sensitization.
Ray U et al.·J Exp Clin Cancer Res
2021
Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis.
Taketomi Y et al.·Nat Immunol
2013
TAT&RGD Peptide-Modified Naringin-Loaded Lipid Nanoparticles Promote the Osteogenic Differentiation of Human Dental Pulp Stem Cells.
Zheng CY et al.·Int J Nanomedicine
2022
Comprehensive exploration of programmed cell death landscape in lung adenocarcinoma combining multi-omic analysis and experimental verification.
Yu P et al.·Sci Rep
2025
Identification of gene expression levels in primary melanoma associated with clinically meaningful characteristics.
Gorlov I et al.·Melanoma Res
2018
Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease.
Yeo KK et al.·Catheter Cardiovasc Interv
2018
Myeloid cell differentiation-related gene signature for predicting clinical outcome, immune microenvironment, and treatment response in lung adenocarcinoma.
Wu D et al.·Sci Rep
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools