PLPP3

Chr 1

phospholipid phosphatase 3

Also known as: Dri42, LPP3, PAP2B, PPAP2B, VCIP

NCBI Gene: 8613ENSG00000162407UniProt: O14495

The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. This protein is a membrane glycoprotein localized at the cell plasma membrane. It has been shown to actively hydrolyze extracellular lysophosphatidic acid and short-chain phosphatidic acid. The expression of this gene is found to be enhanced by epidermal growth factor in Hela cells. [provided by RefSeq, Mar 2010]

51
ClinVar variants
10
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PLPP3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 32 VUS of 51 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.38LOEUF
pLI 0.917
Z-score 3.00
OE 0.08 (0.03–0.38)
Highly constrained

More LoF-intolerant than ~75% of genes

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.
1.43Z-score
OE missense 0.71 (0.61–0.82)
134 obs / 189.5 exp
Tolerant

Mild missense constraint

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.0.08 (0.03–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.61–0.82)
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.0.88
0≤1.21.6
LoF obs/exp: 1 / 12.4Missense obs/exp: 134 / 189.5Syn Z: 0.86

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS32
7
Pathogenic
3
Likely Pathogenic
32
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
3
0
3
VUS
0
28
4
0
32
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02814042

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

View in ClinVar →

Protein Context — Lollipop Plot

PLPP3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Polyenylphosphatidylcholine alleviates cardiorenal fibrosis, injury and dysfunction in spontaneously hypertensive rats by regulating Plpp3 signaling.
Zhang Y et al.·Front Cardiovasc Med
2024🔓 Open Access
Phospholipid Phosphatase 3 (PLPP3) Induces Oxidative Stress to Accelerate Ovarian Aging in Pigs.
Quan H et al.·Cells
2024🔓 Open Access
FTO-dependent m6A modification of Plpp3 in circSCMH1-regulated vascular repair and functional recovery following stroke.
Li B et al.·Nat Commun
2023🔓 Open AccessFunctional
Plpp3, a novel regulator of pluripotency exit and endodermal differentiation of mouse embryonic stem cells.
Montané-Romero ME et al.·Biol Open
2023🔓 Open AccessFunctional
Coronary Artery Disease Risk-Associated Plpp3 Gene and Its Product Lipid Phosphate Phosphatase 3 Regulate Experimental Atherosclerosis.
Mueller PA et al.·Arterioscler Thromb Vasc Biol
2019
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