PLD2

Chr 17

phospholipase D2

Also known as: PLD1C

NCBI Gene: 5338ENSG00000129219UniProt: O14939

The protein encoded by this gene catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline. The activity of the encoded enzyme is enhanced by phosphatidylinositol 4,5-bisphosphate and ADP-ribosylation factor-1. This protein localizes to the peripheral membrane and may be involved in cytoskeletal organization, cell cycle control, transcriptional regulation, and/or regulated secretion. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

204
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PLD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 168 VUS of 204 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.
1.06LOEUF
pLI 0.000
Z-score 1.15
OE 0.83 (0.66–1.06)
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.
0.12Z-score
OE missense 0.99 (0.92–1.06)
577 obs / 585.1 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.0.83 (0.66–1.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.92–1.06)
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.1.01
0≤1.21.6
LoF obs/exp: 46 / 55.2Missense obs/exp: 577 / 585.1Syn Z: -0.15

ClinVar Variant Classifications

204 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS168
Likely Benign8
Benign6
21
Pathogenic
1
Likely Pathogenic
168
VUS
8
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
1
156
11
0
168
Likely Benign
0
5
1
2
8
Benign
0
3
2
1
6
Total1164363204

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

View in ClinVar →

Protein Context — Lollipop Plot

PLD2 · 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
PHOSPHOLIPASE D2; PLD2
MIM #602384 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Syntenin and syndecan in the biogenesis of exosomes.
Friand V et al.·Biol Cell
2015Review
RNA binding protein RALY facilitates colorectal cancer metastasis via enhancing exosome biogenesis in m6A dependent manner.
Zhou J et al.·Int J Biol Macromol
2024
Essential role of PLD2 in hypoxia-induced stemness and therapy resistance in ovarian tumors.
Muñoz-Galván S et al.·J Exp Clin Cancer Res
2024
HIF1α/PLD2 axis linked to glycolysis induces T-cell immunity in oral lichen planus.
Wang F et al.·Biochim Biophys Acta Gen Subj
2020
Targeting phospholipase D in cancer, infection and neurodegenerative disorders.
Brown HA et al.·Nat Rev Drug Discov
2017Review
Phospholipase D2: A biomarker implicated in various pancreatic diseases beyond acute pancreatitis.
Tornel Avelar AI et al.·World J Gastroenterol
2025
The phospholipase D superfamily as therapeutic targets.
Frohman MA·Trends Pharmacol Sci
2015Review
Astragaloside IV Alleviates Colorectal Cancer Metastases by Regulating RALY/PLD2 Axis and Inhibiting Tumoral Exosome Biogenesis.
Li L et al.·Phytother Res
2026
[Phospholipase D: its role in metabolism processes and disease development].
Ramenskaia GV et al.·Biomed Khim
2018Review
Exosome Secretion and Epithelial-Mesenchymal Transition in Ovarian Cancer Are Regulated by Phospholipase D.
Onallah H et al.·Int J Mol Sci
2022
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