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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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PLCD1
phospholipase C delta 1
Chromosome 3 Β· 3p22.2
NCBI Gene: 5333Ensembl: ENSG00000187091.15HGNC: HGNC:9060UniProt: A0A384MR47
102PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
phosphatidylinositol-4,5-bisphosphate phospholipase C activityextracellular exosomecytoplasmic side of plasma membraneprotein bindingnonsyndromic congenital nail disorder 3Epidermal Inclusion Cystsebaceous gland diseasetrichilemmal cyst
✦AI Summary

PLCD1 (phospholipase C delta 1) is a phosphatidylinositol-specific phospholipase C enzyme that mediates production of the second messengers diacylglycerol and inositol 1,4,5-trisphosphate 1, binding phosphatidylinositol 4,5-bisphosphate to regulate intracellular signaling 2. The enzyme is essential for trophoblast and placental development and plays critical roles in calcium homeostasis and intracellular movement. PLCD1 functions as a tumor suppressor in multiple cancer types. In breast cancer, PLCD1 is frequently downregulated through promoter methylation (52-78% of tumors), and ectopic expression inhibits proliferation, induces apoptosis, and triggers G2/M cell cycle arrest 34. Similarly, in esophageal squamous cell carcinoma, PLCD1 suppresses proliferation, invasion, and migration via inhibition of Wnt/Ξ²-catenin signaling 5. In cardiovascular disease, the MIR503HG/miR-191-5p/PLCD1 pathway regulates apoptosis and inflammation in abdominal aortic aneurysm 6. Germline PLCD1 mutations cause non-syndromic congenital nail disorder and familial skin appendage tumors. Gain-of-function variants increase enzymatic activity, promoting keratinocyte proliferation through PKC/PKD/ERK1/2 pathway activation and TRPV6 channel closure, leading to pilomatricomas 7. PLCD1 knockout mice exhibit progressive hair loss and hair follicle abnormalities, demonstrating its essential role in hair development 8.

Sources cited
1
PLCD1 mediates production of second messengers diacylglycerol and inositol 1,4,5-trisphosphate
PMID: 9188725
2
PLCD1 binds phosphatidylinositol 4,5-bisphosphate
PMID: 7890667
3
PLCD1 is a tumor suppressor with frequent promoter methylation in breast cancer that induces G2/M arrest
PMID: 20657189
4
PLCD1 overexpression inhibits breast cancer cell proliferation through apoptosis induction and migration suppression
PMID: 25655282
5
PLCD1 suppresses esophageal squamous cell carcinoma proliferation via Wnt/Ξ²-catenin pathway inhibition
PMID: 32236884
6
PLCD1 is regulated by the MIR503HG/miR-191-5p axis in abdominal aortic aneurysm pathogenesis
PMID: 37228901
7
Germline PLCD1 gain-of-function variants cause multiple pilomatricomas through PKC/PKD/ERK1/2 pathway activation
PMID: 32795530
8
PLCD1 knockout causes progressive hair loss and hair follicle abnormalities in mice
PMID: 29793503
9
PLCD1 gene expression is regulated by neuropeptide Y in endothelial cells
PMID: 24903829
Disease Associationsβ“˜21
nonsyndromic congenital nail disorder 3Open Targets
0.63Moderate
Epidermal Inclusion CystOpen Targets
0.49Moderate
sebaceous gland diseaseOpen Targets
0.44Moderate
trichilemmal cystOpen Targets
0.44Moderate
Follicular CystOpen Targets
0.43Moderate
hair anomalyOpen Targets
0.43Moderate
osteoarthritis, hipOpen Targets
0.43Moderate
skin appendage disorderOpen Targets
0.37Weak
leukonychia totalisOpen Targets
0.37Weak
osteoarthritisOpen Targets
0.34Weak
skin diseaseOpen Targets
0.34Weak
total hip arthroplastyOpen Targets
0.34Weak
Alzheimer diseaseOpen Targets
0.13Weak
breast cancerOpen Targets
0.08Suggestive
chondrosarcomaOpen Targets
0.07Suggestive
oral squamous cell carcinomaOpen Targets
0.07Suggestive
renal cell carcinomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
triple-negative breast cancerOpen Targets
0.06Suggestive
lung adenocarcinomaOpen Targets
0.06Suggestive
Nail disorder, non-syndromic congenital, 3UniProt
Pathogenic Variants8
NM_006225.4(PLCD1):c.1588C>T (p.Arg530Ter)Pathogenic
not provided|Nonsyndromic congenital nail disorder 3
β˜…β˜…β˜†β˜†2023β†’ Residue 530
NM_006225.4(PLCD1):c.992G>A (p.Arg331Gln)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 331
NM_006225.4(PLCD1):c.1483del (p.Met495fs)Likely pathogenic
PLCD1-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 495
NM_006225.4(PLCD1):c.1738C>T (p.Gln580Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 580
NM_006225.4(PLCD1):c.1155dup (p.Ile386fs)Likely pathogenic
PLCD1-related disorder
β˜†β˜†β˜†β˜†2024β†’ Residue 386
NM_006225.4(PLCD1):c.1724-5_1728delPathogenic
Nonsyndromic congenital nail disorder 3
β˜†β˜†β˜†β˜†2011
NM_006225.4(PLCD1):c.562T>C (p.Cys188Arg)Pathogenic
Nonsyndromic congenital nail disorder 3
β˜†β˜†β˜†β˜†2011β†’ Residue 188
NM_006225.4(PLCD1):c.1246C>T (p.Arg416Ter)Pathogenic
Nonsyndromic congenital nail disorder 3
β˜†β˜†β˜†β˜†2011β†’ Residue 416
View on ClinVar β†—
Related Genes
PRKCAProtein interaction96%PRKCBProtein interaction95%PI4K2BProtein interaction95%PI4K2AProtein interaction94%PIKFYVEProtein interaction94%PTENProtein interaction93%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
79%
Lung
59%
Heart
41%
Liver
35%
Brain
22%
Gene Interaction Network
Click a node to explore
PLCD1PRKCAPRKCBPI4K2BPI4K2APIKFYVEPTEN
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P51178
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.95LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.65–0.95]
RankingsWhere PLCD1 stands among ~20K protein-coding genes
  • #4,688of 20,598
    Most Researched102 Β· top quartile
  • #3,055of 5,498
    Most Pathogenic Variants8
  • #8,944of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedPLCD1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer.
PMID: 25655282
Exp Cell Res Β· 2015
1.00
2
PLCD1 and Pilar Cysts.
PMID: 31543210
J Invest Dermatol Β· 2019
0.90
3
Germline Mutation of PLCD1 Contributes to Human Multiple Pilomatricomas through Protein Kinase D/Extracellular Signal-Regulated Kinase1/2 Cascade and TRPV6.
PMID: 32795530
J Invest Dermatol Β· 2021
0.80
4
PLCD1 Suppressed Cellular Proliferation, Invasion, and Migration via Inhibition of Wnt/Ξ²-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma.
PMID: 32236884
Dig Dis Sci Β· 2021
0.70
5
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].
PMID: 35149087
Exp Cell Res Β· 2022
0.60