Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

PLCD1 (phospholipase C, delta 1)

Written2011-01Xiaotong Hu
Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China

(Note : for Links provided by Atlas : click)


HGNC Alias name"1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1
 Phospholipase C ??1"
HGNC Previous name"phospholipase C, delta 1"
LocusID (NCBI) 5333
Atlas_Id 43927
Location 3p22.2  [Link to chromosome band 3p22]
Location_base_pair Starts at 38007496 and ends at 38029642 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PLCD1.png]
Local_order The PLCD1 gene is located between the VILL gene and the DLEC1 gene.
  PLCD1 starts at 38048987 bp and ends at 38071253 bp from pter on Chr3p22-p21.3 and located between VILL and DLEC1 gene.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
GAPDH (12p13.31) / PLCD1 (3p22.2)INS-IGF2 (11p15.5) / PLCD1 (3p22.2)


  Closed and opened boxes represent coding and non-coding sequences of PLCD1 gene, respectively.
Description The PLCD1 gene is a functioning gene and contains 15 exons and spans 22.17 kb.
Transcription The variant 1 (NM_001130964) encodes the longer isoform 1 (NP_001124436). The variant 2 (NM_006225.3) contains an alternate 5' terminal exon compared to transcript variant 1, and initiates translation from an in-frame upstream AUG, resulting in a shorter isoform 2 (NP_006216) with a different N-terminus compared to isoform 1.


  Protein domain organization of the mammalian PLCD1.
Description The deduced 777-amino acid isoform 1 (NM_001130964) and 756-amino acid isoform 2 (NP_006216) shares 95% sequence homology with the rat protein. They contain a N-terminal PH domain, 2 EF-hand1 domains, PI-PLC X-box, PI-PLC Y-box and C2 region.
Expression Expressed high or medium in CNS (brain), hematopoietic (blood), liver and pancreas, digestive (GI-tract), respiratory (lung), male and female tissues, placenta, urinary tract (kidney) skin and soft tissues but no expression in cardio vascular and endocrine tissues.
Localisation Intracellular: cytoplasm and nucleus.
Function Catalyzing the hydrolysis of phosphatidylinositol 4,5 biphosphate to generate diacylglycerol and inositol 1,4,5 triphosphate. Mediating a wide variety of cellular stimuli. Shuttling between the nucleus and the cytoplasm, and nuclear import is mediated by its Ca2+-dependent interaction with importin beta 1. Playing an important suppressive role in the development and progression of cancers such as esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC).
Homology The PLCD1 gene is conserved in dog, cow, mouse, rat, chicken, zebrafish, and A. thaliana.


  The mutation location is highlighted in red and this mutation occured in 17% (1/6) skin samples.
AA Mutation: p.E226K (Substitution - Missense).
CDS Mutation: c.676G>A (Substitution).

Implicated in

Entity Esophageal squamous cell carcinoma
Prognosis Firstly, four commonly deleted regions (CDRs) at 3p26.3, 3p22, 3p21.3 and 3p14.2 were identified. Absent and down-regulated expression of several candidate TSGs, including CHL1, PCAF, RBMS3, PLCD1 and CACNA2D3, were detected in primary ESCC tumors and ESCC cell lines. These results provided evidence that minimal deleted regions at 3p26.3, 3p22, 3p21.3 and 3p14.2 containing potential TSGs may contribute to the pathogenesis of esophageal cancer.
Secondly, absent expression of PLC delta 1 was detected in 26 of 50 (52%) primary ESCCs and 4 of 9 (44.4%) ESCC cell lines, which was significantly associated with DNA copy number loss and promoter hypermethylation (P < 0.05). Functional studies showed that PLC delta 1 was able to suppress both in vitro and in vivo tumorigenic ability of ESCC cells, including foci formation, colony formation in soft agar, and tumor formation in nude mice. The tumor-suppressive mechanism of PLC delta 1 was associated with its role in the cell cycle arrest at the G(1)-S checkpoint by up-regulation of p21 and down-regulation of phosphorylated Akt (Ser(473)). In addition, down-regulation of PLC delta 1 protein was significantly correlated with ESCC metastasis (P = 0.014), which was associated with its function in increasing cell adhesion and inhibiting cell mobility. These results suggest that PLC delta 1 plays an important suppressive role in the development and progression of ESCC.
Entity Breast carcinoma
Prognosis PLCD1 are more highly expressed in the transformed cell lines compared to MCF-10A. To test whether PLCd1 or PLCd3 played any role in tumor cell proliferation or cell migration. RNAi mediated knockdown of PLCD1 reduced proliferation of the MDA-MB-231 cells. Morphological changes including cell rounding, and surface blebbing and nuclear fragmentation were observed. These changes were accompanied by reductions in cell migration activities. On the other hand, PLCD1 knockdown failed to cause comparable morphological changes in the normal MCF-10A line, but did reduce cell proliferation and migration. Taken together, these data are consistent with the idea that PLCD1 support the growth and migration of normal and neoplastic mammary epithelial cells in vitro.
However there is contrasted results published in another paper. Their results suggested that PLCD1 is a functional tumor suppressor inducing G(2)/M arrest and frequently methylated in breast cancer.
Entity Gastric cancer
Prognosis Located at the important tumor suppressor locus, 3p22, PLCD1 encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. We identified PLCD1 as a downregulated gene in aerodigestive carcinomas through expression profiling and epigenetic characterization. We found that PLCD1 was expressed in all normal adult tissues but low or silenced in 84% (16/19) gastric cancer cell lines, well correlated with its CpG island (CGI) methylation status. Methylation was further detected in 62% (61/98) gastric primary tumors, but none of normal gastric mucosa tissues. PLCD1 methylation was significantly correlated with tumor high stage. Detailed methylation analysis of 37 CpG sites at the PLCD1 CGI by bisulfite genomic sequencing confirmed its methylation. PLCD1 silencing could be reversed by pharmacological demethylation with 5-aza-2'-deoxycytidine, indicating a direct epigenetic silencing. Ectopic expression of PLCD1 in silenced gastric tumor cells dramatically inhibited their clonogenicity and migration, possibly through downregulating MMP7 expression and hampering the reorganization of cytoskeleton through cofilin inactivation by phosphorylation. Thus, epigenetic inactivation of PLCD1 is common and tumor-specific in gastric cancer, and PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis.
Entity Colon carcinomas
Prognosis Decreased levels of the PLC delta 1 protein were seen in most colon carcinomas (12 of 13 paired samples) and PLC delta 1 protein was not detected in any of the carcinoma cell lines.
Entity Rat colon neoplasms
Prognosis The expression of PLC-delta expression in rat colon neoplasms induced by methylazoxymethanol (MAM) acetate was examined. Large-bowel neoplasms were observed in five of 10 rats given MAM acetate 40 weeks after treatment. PLC-delta expression in the neoplasms was not detected by northern blot analysis, and a low level of expression was detected by immunoblot analysis, although PLC-delta expression was apparent in the non-neoplastic colon mucosae of MAM acetate-treated rats as well as in the colon mucosae of control rats.
Entity Insulinoma
Note Insulinoma MIN6 cells.
Prognosis To study the effects of enhanced phosphoinositide hydrolysis on insulin secretion, phosphoinositide-specific phospholipase Cbeta1 (PLCbeta1) or PLCdelta1 was overexpressed in insulinoma MIN6 cells via adenoviral vectors. Inositol phosphate production stimulated by KCl or glucose in both PLCbeta1- and PLCdelta1-overexpressing cells were greater than that in control cells, reduced phosphatidylinositol-4,5-bisphosphate levels were observed in these cells stimulated by NaF or KCl. These data suggest that excessive phosphoinositide hydrolysis inhibits secretagogue-induced insulin release in MIN6 cells.
Entity Pheochromocytoma
Note Pheochromocytoma PC12 cells.
Prognosis PLCD1 is recruited from the cytoplasm to lipid rafts after CCH-induced Ca2+ mobilization following the activation of PLCbeta by GPCR and PLCD1 is activated only in lipid rafts by localized capacitative entry of extracellular Ca2+. PLCD1, p122RhoGAP and RhoA in combination could constitute a unique functional unit for the regulation of both phosphoinositide/Ca2+ signaling and the actin cytoskeleton in the periphery of specified membrane domains. This would provide further insights into the molecular mechanisms of cancer development.


Characterization of a novel tumor-suppressor gene PLC delta 1 at 3p22 in esophageal squamous cell carcinoma.
Fu L, Qin YR, Xie D, Hu L, Kwong DL, Srivastava G, Tsao SW, Guan XY.
Cancer Res. 2007 Nov 15;67(22):10720-6.
PMID 18006814
Phospholipase C delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer.
Hu XT, Zhang FB, Fan YC, Shu XS, Wong AH, Zhou W, Shi QL, Tang HM, Fu L, Guan XY, Rha SY, Tao Q, He C.
Oncogene. 2009 Jul 2;28(26):2466-75. Epub 2009 May 18.
PMID 19448674
Enhanced phosphoinositide hydrolysis via overexpression of phospholipase C beta1 or delta1 inhibits stimulus-induced insulin release in insulinoma MIN6 cells.
Ishihara H, Wada T, Kizuki N, Asano T, Yazaki Y, Kikuchi M, Oka Y.
Biochem Biophys Res Commun. 1999 Jan 8;254(1):77-82.
PMID 9920735
Genomic structure of the human PLCD1 (phospholipase C delta 1) locus on 3p22-->p21.3.
Ishikawa S, Takahashi T, Ogawa M, Nakamura Y.
Cytogenet Cell Genet. 1997;78(1):58-60.
PMID 9345909
Expression of phospholipases gamma 1, beta 1, and delta 1 in primary human colon carcinomas and colon carcinoma cell lines.
Nomoto K, Tomita N, Miyake M, Xhu DB, LoGerfo PR, Weinstein IB.
Mol Carcinog. 1995 Mar;12(3):146-52.
PMID 7893368
Single-nucleotide polymorphism-mass array reveals commonly deleted regions at 3p22 and 3p14.2 associate with poor clinical outcome in esophageal squamous cell carcinoma.
Qin YR, Fu L, Sham PC, Kwong DL, Zhu CL, Chu KK, Li Y, Guan XY.
Int J Cancer. 2008 Aug 15;123(4):826-30.
PMID 18508313
Expression and function of phospholipase C in breast carcinoma.
Rebecchi MJ, Raghubir A, Scarlata S, Hartenstine MJ, Brown T, Stallings JD.
Adv Enzyme Regul. 2009;49(1):59-73. Epub 2009 Jan 20.
PMID 19344632
PLCD1 is a functional tumor suppressor inducing G(2)/M arrest and frequently methylated in breast cancer.
Xiang T, Li L, Fan Y, Jiang Y, Ying Y, Putti TC, Tao Q, Ren G.
Cancer Biol Ther. 2010 Sep;10(5):520-7. Epub 2010 Sep 21.
PMID 20657189
Recruitment and activation of phospholipase C (PLC)-delta1 in lipid rafts by muscarinic stimulation of PC12 cells: contribution of p122RhoGAP/DLC1, a tumor-suppressing PLCdelta1 binding protein.
Yamaga M, Kawai K, Kiyota M, Homma Y, Yagisawa H.
Adv Enzyme Regul. 2008;48:41-54. Epub 2007 Nov 19.
PMID 18157946
Reduced expression of phospholipase C-delta, a signal-transducing enzyme, in rat colon neoplasms induced by methylazoxymethanol acetate.
Yoshimi N, Wang A, Makita H, Suzui M, Mori H, Okano Y, Banno Y, Nozawa Y.
Mol Carcinog. 1994 Dec;11(4):192-6.
PMID 7528022


This paper should be referenced as such :
Hu, X
PLCD1 (phospholipase C, delta 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(8):670-673.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)PLCD1   9060
Entrez_Gene (NCBI)PLCD1    phospholipase C delta 1
GeneCards (Weizmann)PLCD1
Ensembl hg19 (Hinxton)ENSG00000187091 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000187091 [Gene_View]  ENSG00000187091 [Sequence]  chr3:38007496-38029642 [Contig_View]  PLCD1 [Vega]
ICGC DataPortalENSG00000187091
TCGA cBioPortalPLCD1
Genatlas (Paris)PLCD1
SOURCE (Princeton)PLCD1
Genetics Home Reference (NIH)PLCD1
Genomic and cartography
GoldenPath hg38 (UCSC)PLCD1  -     chr3:38007496-38029642 -  3p22.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PLCD1  -     3p22.2   [Description]    (hg19-Feb_2009)
GoldenPathPLCD1 - 3p22.2 [CytoView hg19]  PLCD1 - 3p22.2 [CytoView hg38]
genome Data Viewer NCBIPLCD1 [Mapview hg19]  
OMIM151600   602142   
Gene and transcription
Genbank (Entrez)AB209862 AK090774 AK098690 AK127813 AK292324
RefSeq transcript (Entrez)NM_001130964 NM_006225
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PLCD1
Alternative Splicing GalleryENSG00000187091
Gene ExpressionPLCD1 [ NCBI-GEO ]   PLCD1 [ EBI - ARRAY_EXPRESS ]   PLCD1 [ SEEK ]   PLCD1 [ MEM ]
Gene Expression Viewer (FireBrowse)PLCD1 [ Firebrowse - Broad ]
GenevisibleExpression of PLCD1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5333
GTEX Portal (Tissue expression)PLCD1
Human Protein AtlasENSG00000187091-PLCD1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP51178   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP51178  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP51178
Splice isoforms : SwissVarP51178
Catalytic activity : Enzyme3.1.4.11 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   [ MEROPS ]
Domaine pattern : Prosite (Expaxy)C2 (PS50004)    EF_HAND_1 (PS00018)    EF_HAND_2 (PS50222)    PH_DOMAIN (PS50003)    PIPLC_X_DOMAIN (PS50007)    PIPLC_Y_DOMAIN (PS50008)   
Domains : Interpro (EBI)C2_dom    C2_domain_sf    EF-hand-dom_pair    EF_Hand_1_Ca_BS    EF_hand_dom    PH-like_dom_sf    PH_domain    PI-PLC_fam    PLC-delta1    PLC-like_Pdiesterase_TIM-brl    PLC_EF-hand-like    PLipase_C_PInositol-sp_X_dom    PLipase_C_Pinositol-sp_Y   
Domain families : Pfam (Sanger)C2 (PF00168)    EF-hand_like (PF09279)    PI-PLC-X (PF00388)    PI-PLC-Y (PF00387)   
Domain families : Pfam (NCBI)pfam00168    pfam09279    pfam00388    pfam00387   
Domain families : Smart (EMBL)C2 (SM00239)  EFh (SM00054)  PH (SM00233)  PLCXc (SM00148)  PLCYc (SM00149)  
Conserved Domain (NCBI)PLCD1
Blocks (Seattle)PLCD1
Human Protein Atlas [tissue]ENSG00000187091-PLCD1 [tissue]
Peptide AtlasP51178
IPIIPI00746030   IPI00016461   
Protein Interaction databases
IntAct (EBI)P51178
Ontologies - Pathways
Ontology : AmiGO"angiogenesis  phosphatidylinositol phospholipase C activity  calcium ion binding  phosphatidylinositol-4,5-bisphosphate binding  cytoplasm  cytosol  plasma membrane  phospholipid metabolic process  lipid catabolic process  GTPase activating protein binding  regulation of cell proliferation  inositol phosphate metabolic process  phosphatidylinositol-mediated signaling  labyrinthine layer blood vessel development  extracellular exosome"  
Ontology : EGO-EBI"angiogenesis  phosphatidylinositol phospholipase C activity  calcium ion binding  phosphatidylinositol-4,5-bisphosphate binding  cytoplasm  cytosol  plasma membrane  phospholipid metabolic process  lipid catabolic process  GTPase activating protein binding  regulation of cell proliferation  inositol phosphate metabolic process  phosphatidylinositol-mediated signaling  labyrinthine layer blood vessel development  extracellular exosome"  
Pathways : KEGGInositol phosphate metabolism    Calcium signaling pathway    Phosphatidylinositol signaling system    Thyroid hormone signaling pathway   
REACTOMEP51178 [protein]
REACTOME PathwaysR-HSA-1855204 [pathway]   
NDEx NetworkPLCD1
Atlas of Cancer Signalling NetworkPLCD1
Wikipedia pathwaysPLCD1
Orthology - Evolution
GeneTree (enSembl)ENSG00000187091
Phylogenetic Trees/Animal Genes : TreeFamPLCD1
Homologs : HomoloGenePLCD1
Homology/Alignments : Family Browser (UCSC)PLCD1
Gene fusions - Rearrangements
Fusion Cancer (Beijing)GAPDH [12p13.31]  -  PLCD1 [3p22.2]  [FUSC001361]
Fusion : FusionGDB3.1.4.11   
Fusion : Fusion_HubGAPDH--PLCD1    INS-IGF2--PLCD1    NKAIN4--PLCD1    PLCD1--CORO1B   
Fusion : QuiverPLCD1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPLCD1 [hg38]
Exome Variant ServerPLCD1
GNOMAD BrowserENSG00000187091
Varsome BrowserPLCD1
Genomic Variants (DGV)PLCD1 [DGVbeta]
DECIPHERPLCD1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPLCD1 
ICGC Data PortalPLCD1 
TCGA Data PortalPLCD1 
Broad Tumor PortalPLCD1
OASIS PortalPLCD1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPLCD1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPLCD1
Mutations and Diseases : HGMDPLCD1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PLCD1
DgiDB (Drug Gene Interaction Database)PLCD1
DoCM (Curated mutations)PLCD1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PLCD1 (select a term)
NCG6 (London) select PLCD1
Cancer3DPLCD1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM151600    602142   
Genetic Testing Registry PLCD1
NextProtP51178 [Medical]
Target ValidationPLCD1
Huge Navigator PLCD1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA33388
Pharm GKB PathwaysPA152530845   
Clinical trialPLCD1
canSAR (ICR)PLCD1 (select the gene name)
DataMed IndexPLCD1
PubMed83 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Feb 19 17:57:46 CET 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us