PLCD3

Chr 17

phospholipase C delta 3

Also known as: PLC-delta-3

NCBI Gene: 113026UniProt: Q8N3E9

This gene encodes a member of the phospholipase C family, which catalyze the hydrolysis of phosphatidylinositol 4,5-bisphosphate to generate the second messengers diacylglycerol and inositol 1,4,5-trisphosphate (IP3). Diacylglycerol and IP3 mediate a variety of cellular responses to extracellular stimuli by inducing protein kinase C and increasing cytosolic Ca(2+) concentrations. This enzyme localizes to the plasma membrane and requires calcium for activation. Its activity is inhibited by spermine, sphingosine, and several phospholipids. [provided by RefSeq, Jul 2008]

0
Active trials
10
Pathogenic / LP
126
ClinVar variants
2
Pubs (1 yr)
1.6
Missense Z
0.81
LOEUF
Clinical Summary— PLCD3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 116 VUS of 126 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

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.
0.81LOEUF
pLI 0.000
Z-score 2.34
OE 0.54 (0.36–0.81)
Tolerant

Typical tolerance to LoF variation

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.
1.59Z-score
OE missense 0.79 (0.72–0.86)
362 obs / 457.7 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.0.54 (0.36–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.72–0.86)
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.0.84
0≤1.21.6
LoF obs/exp: 16 / 29.8Missense obs/exp: 362 / 457.7Syn Z: 1.75

ClinVar Variant Classifications

126 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS116
10
Pathogenic
116
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
114
2
0
116
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0114120126

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

View in ClinVar →

Protein Context — Lollipop Plot

PLCD3 · 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 Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Etiology and Pathogenesis of Hemifacial Microsomia.
Chen Q et al.·J Dent Res
2018Review
LncRNA PLCD3-OT1 Functions as a CeRNA to Prevent Age-Related Cataract by Sponging miR-224-5p and Regulating PLCD3 Expression.
Xiang J et al.·Invest Ophthalmol Vis Sci
2019
Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.
Mei Z et al.·Alzheimers Dement
2025
Phospholipase C Delta 3 inhibits apoptosis and promotes proliferation, migration, and invasion of thyroid cancer cells via Hippo pathway.
Lin L et al.·Acta Biochim Biophys Sin (Shanghai)
2021
Analysis of the regulatory role of miR-34a-5p/PLCD3 in the progression of osteoarthritis.
Ying P et al.·Funct Integr Genomics
2023
Phosphoinositide cycle gene polymorphisms affect the plasma lipid profile in the Quebec Family Study.
Dolley G et al.·Mol Genet Metab
2009
Noteworthy prognostic value of phospholipase C delta genes in early stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy and potential molecular mechanisms.
Zhou X et al.·Cancer Med
2020Cohort
A novel telomere-related gene prognostic signature for survival and drug treatment efficiency prediction in lung adenocarcinoma.
Chen H et al.·Aging (Albany NY)
2023
Digital gene expression analysis might aid in the diagnosis of thyroid cancer.
Armanious H et al.·Curr Oncol
2020
Common variants in or near FGF5, CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans.
Liu C et al.·J Hypertens
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients