TISIDB

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm, perinuclear region Endoplasmic reticulum membrane Lipid-anchor Cytoplasmic side Golgi apparatus membrane Lipid-anchor Cytoplasmic side Late endosome membrane Lipid-anchor Cytoplasmic side
Domain	PF00169 PH domain PF00614 Phospholipase D Active site motif PF13091 PLD-like domain PF00787 PX domain
Function	Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0006654 phosphatidic acid biosynthetic process GO:0007265 Ras protein signal transduction GO:0016042 lipid catabolic process GO:0030031 cell projection assembly GO:0030033 microvillus assembly GO:0032528 microvillus organization GO:0032530 regulation of microvillus organization GO:0032534 regulation of microvillus assembly GO:0046473 phosphatidic acid metabolic process GO:0048017 inositol lipid-mediated signaling GO:0060491 regulation of cell projection assembly
Molecular Function	GO:0004620 phospholipase activity GO:0004630 phospholipase D activity GO:0005543 phospholipid binding GO:0008081 phosphoric diester hydrolase activity GO:0016298 lipase activity GO:0035091 phosphatidylinositol binding GO:0042578 phosphoric ester hydrolase activity GO:0070290 N-acylphosphatidylethanolamine-specific phospholipase D activity
Cellular Component	GO:0005765 lysosomal membrane GO:0005770 late endosome GO:0010008 endosome membrane GO:0016324 apical plasma membrane GO:0030139 endocytic vesicle GO:0031902 late endosome membrane GO:0044440 endosomal part GO:0045177 apical part of cell GO:0098852 lytic vacuole membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04014 Ras signaling pathway hsa04024 cAMP signaling pathway hsa04071 Sphingolipid signaling pathway hsa04144 Endocytosis hsa04666 Fc gamma R-mediated phagocytosis hsa04724 Glutamatergic synapse hsa04912 GnRH signaling pathway hsa00564 Glycerophospholipid metabolism hsa00565 Ether lipid metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis R-HSA-1483206: Glycerophospholipid biosynthesis R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-6798695: Neutrophil degranulation R-HSA-1483257: Phospholipid metabolism R-HSA-2029485: Role of phospholipids in phagocytosis R-HSA-1483166: Synthesis of PA R-HSA-1483148: Synthesis of PG

> KEGG and Reactome Pathway

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KEGG

hsa04014 Ras signaling pathway
hsa04024 cAMP signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04144 Endocytosis
hsa04666 Fc gamma R-mediated phagocytosis
hsa04724 Glutamatergic synapse
hsa04912 GnRH signaling pathway
hsa00564 Glycerophospholipid metabolism
hsa00565 Ether lipid metabolism
hsa01100 Metabolic pathways

Reactome

R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-1483206: Glycerophospholipid biosynthesis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-6798695: Neutrophil degranulation
R-HSA-1483257: Phospholipid metabolism
R-HSA-2029485: Role of phospholipids in phagocytosis
R-HSA-1483166: Synthesis of PA
R-HSA-1483148: Synthesis of PG

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PLD1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between PLD1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23804711	Chronic Lymphocytic Leukemia	Promote immunity	Transendothelial migration (TEM) of normal lymphocytes into lymph nodes requires the chemokine-induced activation of Rap1 and αLβ2 integrin. However, in most cases of CLL, Rap1 is refractory to chemokine stimulation, resulting in failed αLβ2 activation and TEM unless α4β1 is coexpressed. In this study, we show that the inability of CXCL12 to induce Rap1 GTP loading in CLL cells results from failure of Rap1-containing endosomes to translocate to the plasma membrane. Taken together, our findings indicate that chemokine unresponsiveness in CLL lymphocytes results from failure of Arf1/phospholipase D1-mediated translocation of Rap1 to the plasma membrane for GTP loading and may be a specific feature of anergy induced by DNA Ags.

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of PLD1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of PLD1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.628	0.112
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.232	0.337
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.196	0.822
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.405	0.152
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.803	0.637
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.099	0.964
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.244	0.602
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.573	0.679
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.111	0.942
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.35	0.731
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.966	0.516
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.301	0.00971

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PLD1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	4.1	-0.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PLD1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PLD1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PLD1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PLD1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PLD1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PLD1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PLD1
Name	phospholipase D1, phosphatidylcholine-specific
Aliases	choline phosphatase 1; phosphatidylcholine-hydrolyzing phospholipase D1; hPLD1; PLD 1; Phospholipase D1
Chromosomal Location	3q26
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PLD1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PLD1.

ID	Name	Drug Type	Targets	#Targets
DB00122	Choline	Small Molecule	ACHE, BCHE, CHRNA7, PCYT1A, PCYT1B, PHOSPHO1, PLD1, PLD2	8
DB05301	LAX-101	Small Molecule	CASP1, PLD1	2

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