PLCD1

Chr 3ADAR

phospholipase C delta 1

Also known as: NDNC3, PLC-III

NCBI Gene: 5333ENSG00000187091UniProt: P51178OMIM: 602142

The protein catalyzes hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into second messengers diacylglycerol (DAG) and inositol triphosphate (IP3) for intracellular signal transduction. Mutations cause hereditary leukonychia (nonsyndromic congenital nail disorder), which can be inherited in either autosomal dominant or autosomal recessive patterns. The gene shows very low constraint to loss-of-function variation (pLI near zero), suggesting tolerance to protein-truncating variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismAD/ARLOEUF 1.101 OMIM phenotype
Clinical Summary— PLCD1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 169 VUS of 268 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.02
OE 0.83 (0.62–1.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.24Z-score
OE missense 0.97 (0.90–1.05)
445 obs / 459.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.83 (0.62–1.10)
0≤0.351.4
Missense OE0.97 (0.90–1.05)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 33 / 40.0Missense obs/exp: 445 / 459.6Syn Z: 0.10
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPLCD1-related familial multiple pilomatricomasOTHERAD
limitedPLCD1-related nail disorder, nonsyndromic congenital (leukonychia)OTHERAD
DN
0.5967th %ile
GOF
0.7027th %ile
LOF
0.3260th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

GOFOur results implicate this p.Glu396Lys variant of PLCD1 from germline leading to gain-of-function of PLCd1 as a causative genetic defect in familial multiple pilomatricomas.PMID:32795530

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

268 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic6
VUS169
Likely Benign29
Benign28
Conflicting1
14
Pathogenic
6
Likely Pathogenic
169
VUS
29
Likely Benign
28
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
10
0
14
Likely Pathogenic
4
1
1
0
6
VUS
0
159
10
0
169
Likely Benign
0
11
4
14
29
Benign
0
5
16
7
28
Conflicting
—1
Total71774121247

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

View in ClinVar →

Protein Context — Lollipop Plot

PLCD1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Phospholipase C delta 1 inhibits WNT/beta-catenin and EGFR-FAK-ERK signaling and is disrupted by promoter CpG methylation in renal cell carcinoma
Xie J et al.·Clin Epigenetics
2023
The tumor suppressor activity of DLC1 requires the interaction of its START domain with Phosphatidylserine, PLCD1, and Caveolin-1
Sanchez-Solana B et al.·Mol Cancer
2021
PLCD1: A Potential Therapeutic Target in the Treatment of Esophageal Squamous Cell Carcinoma?
Wang YD et al.·Dig Dis Sci
2021
Case of familial trichilemmal cyst caused by a recurrent monoallelic mutational mechanism in the PLCD1 gene.
Aoki Y et al.·J Dermatol
2024Functional
Corrigendum to "Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer" [Exp Cell Res. 2015 Mar 15; 332(2):179-89].
Mu H et al.·Exp Cell Res
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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