PLD2

Summary

PLD2 (phospholipase D2, HGNC:9068) is a protein-coding gene on chromosome 17p13.2, encoding Phospholipase D2 (O14939). Function as phospholipase selective for phosphatidylcholine.

The protein encoded by this gene catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline. The activity of the encoded enzyme is enhanced by phosphatidylinositol 4,5-bisphosphate and ADP-ribosylation factor-1. This protein localizes to the peripheral membrane and may be involved in cytoskeletal organization, cell cycle control, transcriptional regulation, and/or regulated secretion. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5338 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 187 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9068
Approved symbol	PLD2
Name	phospholipase D2
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000129219
Ensembl biotype	protein_coding
OMIM	602384
Entrez	5338

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 12 protein_coding, 8 retained_intron, 2 nonsense_mediated_decay

ENST00000263088, ENST00000571273, ENST00000572127, ENST00000572199, ENST00000572940, ENST00000573258, ENST00000574268, ENST00000574796, ENST00000575246, ENST00000575316, ENST00000575813, ENST00000575945, ENST00000576329, ENST00000576864, ENST00000576983, ENST00000879130, ENST00000879131, ENST00000879132, ENST00000879133, ENST00000928900, ENST00000964340, ENST00000964341

RefSeq mRNA: 2 — MANE Select: NM_002663 NM_001243108, NM_002663

CCDS: CCDS11057, CCDS58507

Canonical transcript exons

ENST00000263088 — 25 exons

Exon	Start	End
ENSE00000676905	4821793	4821907
ENSE00000886994	4819429	4819582
ENSE00001126213	4818297	4818385
ENSE00001126221	4818002	4818106
ENSE00001126318	4808274	4808416
ENSE00001126323	4807984	4808114
ENSE00001360015	4807152	4807225
ENSE00002681387	4822640	4823430
ENSE00003475241	4816620	4816746
ENSE00003484430	4817146	4817259
ENSE00003508147	4810802	4810951
ENSE00003544480	4814633	4814711
ENSE00003545577	4809100	4809205
ENSE00003549859	4809877	4810029
ENSE00003555968	4809298	4809363
ENSE00003590900	4814418	4814501
ENSE00003592063	4816937	4817055
ENSE00003592812	4819084	4819218
ENSE00003603465	4809493	4809551
ENSE00003609127	4809691	4809783
ENSE00003611606	4818774	4818823
ENSE00003614118	4815764	4815934
ENSE00003638098	4815476	4815586
ENSE00003670738	4807772	4807881
ENSE00003676693	4818494	4818607

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5855 / max 84.9924, expressed in 1735 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158945	7.5855	1735

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.17	gold quality
esophagus mucosa	UBERON:0002469	96.67	gold quality
skin of leg	UBERON:0001511	95.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.09	gold quality
ectocervix	UBERON:0012249	94.55	gold quality
right ovary	UBERON:0002118	94.54	gold quality
skin of abdomen	UBERON:0001416	94.53	gold quality
cerebellar hemisphere	UBERON:0002245	94.51	gold quality
cerebellar cortex	UBERON:0002129	94.33	gold quality
minor salivary gland	UBERON:0001830	94.09	gold quality
left ovary	UBERON:0002119	93.88	gold quality
tibial nerve	UBERON:0001323	93.38	gold quality
apex of heart	UBERON:0002098	93.20	gold quality
ventricular zone	UBERON:0003053	93.12	gold quality
mouth mucosa	UBERON:0003729	92.96	gold quality
esophagus	UBERON:0001043	92.88	gold quality
cerebellum	UBERON:0002037	92.74	gold quality
body of uterus	UBERON:0009853	92.64	gold quality
vagina	UBERON:0000996	92.59	gold quality
endocervix	UBERON:0000458	92.35	gold quality
zone of skin	UBERON:0000014	92.28	gold quality
pharyngeal mucosa	UBERON:0000355	92.25	gold quality
vena cava	UBERON:0004087	92.21	gold quality
saliva-secreting gland	UBERON:0001044	91.91	gold quality
right coronary artery	UBERON:0001625	91.69	gold quality
lateral globus pallidus	UBERON:0002476	91.61	gold quality
left uterine tube	UBERON:0001303	91.56	gold quality
right uterine tube	UBERON:0001302	91.40	gold quality
gall bladder	UBERON:0002110	91.11	gold quality
sural nerve	UBERON:0015488	90.94	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.96
E-MTAB-6386	no	275.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EWSR1, FLI1, NFKB

miRNA regulators (miRDB)

29 targeting PLD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-3170	95.84	64.32	721
HSA-MIR-887-3P	94.03	63.71	71
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Literature-anchored findings (GeneRIF, showing 40)

• activation of phospholipases D1 and D2 by S1P regulates the phosphorylation of extracellular-signal-regulated kinase and IL-8 secretion in Beas-2B cells (PMID:12149127)
• localizes to the plasma membrane of mast cells; stimulated by oleic acid (PMID:12374567)
• PLD2 activity is directly regulated by ADP-ribosylation factor 4, and this ARF4-mediated PLD2 activation stimulates AP-1-dependent transcription in the EGF-induced cellular response (PMID:12446727)
• PLD is regulated py phosphoinositides through the PH domain and the polybasic motif (PMID:12486109)
• PLD2 may play a key role in the regulation of agonist-induced endocytosis of the mu-opioid receptor (PMID:12519790)
• Phospholipase D(2) gene is a susceptibility locus for colorectal cancer in Japanese individuals. (PMID:12601529)
• elevated PLD activity generates survival signals allowing cells to overcome default apoptosis programs (PMID:12615079)
• PLD isozymes stimulate cell growth by repressing expression of p21 gene (PMID:12782287)
• phospholipase D2 was enriched in caveolae; PLD2 could be involved in MEK/ERK signaling cascades that are induced by the VEGF/VEGFR-2/PKC-delta pathway in endothelial cells (PMID:14704231)
• PLD2 functions at the plasma membrane to facilitate endocytosis of the angiotensin II type 1 receptor. (PMID:14718562)
• The phospholipase D2 possesses a PH domain, activation by phosphatidylinositol 4,5-disphosphate (PIP2) involves binding to a conserved cluster of basic residues. (PMID:15052337)
• Translocation of PLD2 to EGF-induced membrane ruffles has been observed in HeLa cells when coexpressed with PIP kinase Ialpha. (PMID:15052340)
• phospholipase D isozymes mediate EGCG-induced COX-2 expression through PKC and p38 in immortalized astroglial line and normal astrocyte cells (PMID:15210717)
• findings provide the first description of a mechanism for activation phospholipase D2 in a physiological setting and of a role for Fyn and Fgr in Fc epsilon RI-mediated signaling. (PMID:15282299)
• an increase in local membrane monomeric tubulin concentration inhibits PLD2 activity (PMID:15548524)
• ANP recruits a signal pathway associated with p38 MAPK, NHE-1 and PLD responsible for ROS production, suggesting a possible role for ANP as novel modulator of ROS generation in HepG2 cells (PMID:15665518)
• Phospholipase D2 (PLD2) enhances PKCzeta activity through direct interaction in a lipase activity-independent manner. (PMID:15798205)
• EWS-Fli1 may play a role in the regulation of PDGF-induced tumor proliferation-signaling enzymes via PLD2 expression in Ewing sarcoma cells (PMID:15919668)
• intracellular unsaturated acyl-CoA derivatives destabilize ABCA1 by activating a PLD2 signaling pathway (PMID:16118212)
• These results suggest that intact phosphorylation sites within the MARCKS ED are required for PLD activation and influence both membrane-cytoskeletal organization and cell viability. (PMID:16341931)
• Y(169) & Y(179) are in 2 consensus sites in PLD2 mediating SH2 interaction with Grb2. They are needed for recruiting Sos, but only overexpression of the PLD2 Y179F mutant resulted in more Ras activity, p44/42(Erk) phosphorylation & enhanced DNA synthesis. (PMID:16407827)
• PLD functions as a GTPase activating protein (GAP) through its phox homology domain (PX), which directly activates the GTPase domain of dynamin and increased epidermal growth factor receptor (EGFR) endocytosis at physiological EGF concentrations. (PMID:16622417)
• Data show that the G–>A (Gly901Asp) mutation of the human PLD2 gene results in catalytic inactivation of the encoded protein. (PMID:16824927)
• demonstration of the involvement of PLD1 and PLD2 and its enzymatic activity toward chemokines in the key physiologic process of leukocyte migration (PMID:16873675)
• gene expression is increased by EWS.Fli-1 and FLI-1 by binding to an erythroblast transformation-specific domain of the PLC2 promoter (PMID:16964281)
• Our findings establish a crucial role for PLD2 in the coupling of extracellular signals to Sos-mediated Ras activation, and provide new insights into the spatial coordination of this activation event. (PMID:17486115)
• Thus, LFA-1 acts through PLD2 to reshape the pattern of Ras activation downstream of the TCR (PMID:17486117)
• Plays a major role in promoting HIV-1 long terminal repeat transactivation and virus replication. (PMID:17627030)
• These results demonstrate for the first time that PLD1 and PLD2 isozymes enhance cobalt chlorde-induced COX-2 expression through differential signaling pathways in astroglioma cells. (PMID:17640750)
• Elevated phospholipase D2 is associated with colorectal carcinoma (PMID:17914593)
• Data suggest that recombinant human phospholipase D2 alone cannot induce apoptosis in HL-60 cells, but it can potentiate the apoptosis of HL-60 cells induced by camptothecin. (PMID:17977756)
• These findings indicate the involvement of phospholipase D activation in hBD-2 up-regulation in gingival epithelial cells. (PMID:17986621)
• Protein kinase C-epsilon regulates sphingosine 1-phosphate-mediated migration of human lung endothelial cells through activation of phospholipase D2, protein kinase C-zeta, and Rac1 (PMID:18296444)
• depletion of phospholipase D2 inhibited motility more severely, essential for the maintenance of keratocyte-like locomotion of NBT-II cells, presumably by regulating the actin cytoskeleton. (PMID:18344600)
• Data suggest that PLD2 is an early player upstream of the Ras-ERK1/2-IL-2 pathway in T-cells via phosphatidic acid and diacylglycerol production. (PMID:18423386)
• we present evidence for the presence of both PLD1 and PLD2 in platelets and indicate a role in platelet activation. (PMID:18432522)
• Expression of active PLD2 enhances processes favorable to lymphoma cell metastasis, whereas expression of inactive PLD2 inhibits metastasis. (PMID:18523140)
• The study results suggest that PLD2 is a new substrate of Cdk5 and that the phosphorylation of PLD2 by Cdk5 is involved in epidermal growth factor-dependent insulin secretion. (PMID:18625302)
• Phospholipase D2 is cleaved at two or three sites in the front of N-terminus and maintained anti-apoptotic potency in spite of its cleavage during apoptosis. (PMID:18694819)
• These results demonstrate a role of PLD in hyperoxia-mediated IQGAP1 activation through Rac1 in tyrosine phosphorylation of Src and cortactin, as well as in p47(phox) translocation and reactive oxygen species formation in human lung endothelial cells. (PMID:19366706)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pld2	ENSDARG00000034262
mus_musculus	Pld2	ENSMUSG00000020828
rattus_norvegicus	Pld2	ENSRNOG00000019604
drosophila_melanogaster	Pld	FBGN0286511
caenorhabditis_elegans		WBGENE00004040

Paralogs (1): PLD1 (ENSG00000075651)

Protein

Protein identifiers

Phospholipase D2 — O14939 (reviewed: O14939)

Alternative names: Choline phosphatase 2, PLD1C, Phosphatidylcholine-hydrolyzing phospholipase D2

All UniProt accessions (6): O14939, I3L1F3, I3L222, I3L381, I3L3I7, I3L4R5

UniProt curated annotations — full annotation on UniProt →

Function. Function as phospholipase selective for phosphatidylcholine. May have a role in signal-induced cytoskeletal regulation and/or endocytosis.

Subunit / interactions. Interacts with PIP5K1B. Interacts with EGFR.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by FGR.

Activity regulation. Stimulated by phosphatidylinositol 4,5-bisphosphate and slightly activated by the ADP-ribosylation factor-1 (ARF-1).

Similarity. Belongs to the phospholipase D family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14939-1	PLD2A	yes
O14939-3	PLD2C
O14939-4	PLD2B

RefSeq proteins (2): NP_001230037, NP_002654* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR001736	PLipase_D/transphosphatidylase	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015679	PLipase_D_fam	Family
IPR016555	PLipase_D_euk	Family
IPR025202	PLD-like_dom	Domain
IPR036871	PX_dom_sf	Homologous_superfamily

Pfam: PF00614, PF00787, PF13091

Enzyme classification (BRENDA):

• EC 3.1.4.4 — phospholipase D (BRENDA: 94 organisms, 465 substrates, 320 inhibitors, 67 Km, 27 kcat entries)
• EC 4.2.1.1 — carbonic anhydrase (BRENDA: 178 organisms, 196 substrates, 2137 inhibitors, 263 Km, 291 kcat entries)

Substrate kinetics (BRENDA)

30 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CO2	0.012–4700	194
PHOSPHATIDYLCHOLINE	0.0015–2.5	18
N-PALMITOYL-PHOSPHATIDYLETHANOLAMINE	0.0029–0.045	16
4-NITROPHENYL ACETATE	0.0024–30.53	16
H2CO3	0.434–112.7	16
DIOLEOYL-PHOSPHATIDYLCHOLINE	0.0015–3	4
LYSOPHOSPHATIDYLCHOLINE	1–3	4
HCO3-	9.3–37	4
P-NITROPHENYL ACETATE	3.86–6.8	4
EGG PHOSPHATIDYLCHOLINE	30.2–33.17	2
L-ALPHA-PHOSPHATIDYLCHOLINE	2.71–3.44	2
PHOSPHATIDYL-P-NITROPHENOL	0.075–1.16	2
PHOSPHATIDYLETHANOLAMINE	0.91–4	2
4-NITROPHENYL PHOSPHATE	0.935–2.195	2
1,2-DIBUTYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.16	1

Catalyzed reactions (Rhea), 2 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-sn-glycero-3-phosphate + choline + H(+) (RHEA:14445)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phosphate + choline + H(+) (RHEA:44872)

UniProt features (78 total): strand 23, helix 21, sequence conflict 10, sequence variant 7, turn 7, domain 4, region of interest 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6OHM	X-RAY DIFFRACTION	1.9
6OHO	X-RAY DIFFRACTION	2
6OHP	X-RAY DIFFRACTION	2.6
6OHQ	X-RAY DIFFRACTION	2.69
7SVP	X-RAY DIFFRACTION	2.9
6OHS	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14939-F1	89.55	0.75

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1483148	Synthesis of PG
R-HSA-1483166	Synthesis of PA
R-HSA-2029485	Role of phospholipids in phagocytosis
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle

MSigDB gene sets: 173 (showing top): GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_SYNAPTIC_VESICLE_RECYCLING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, PID_RHOA_PATHWAY, PID_ARF6_DOWNSTREAM_PATHWAY, GOBP_GLYCEROLIPID_METABOLIC_PROCESS

GO Biological Process (12): G protein-coupled receptor internalization (GO:0002031), phosphatidic acid biosynthetic process (GO:0006654), cytoskeleton organization (GO:0007010), small GTPase-mediated signal transduction (GO:0007264), phospholipid catabolic process (GO:0009395), synaptic vesicle recycling (GO:0036465), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), regulation of vesicle-mediated transport (GO:0060627), lipid metabolic process (GO:0006629), receptor-mediated endocytosis (GO:0006898), lipid catabolic process (GO:0016042), intracellular signal transduction (GO:0035556)

GO Molecular Function (5): D-type glycerophospholipase activity (GO:0004630), phosphatidylinositol binding (GO:0035091), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), brush border membrane (GO:0031526), presynapse (GO:0098793), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	2
RHO GTPase cycle	2
Fcgamma receptor (FCGR) dependent phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
desensitization of G protein-coupled receptor signaling pathway	1
receptor internalization	1
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
organelle organization	1
intracellular signaling cassette	1
phospholipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
transport	1
establishment of localization in cell	1
synaptic vesicle cycle	1
Fc receptor mediated stimulatory signaling pathway	1
phagocytosis	1
Fc-gamma receptor signaling pathway	1
vesicle-mediated transport	1
regulation of cellular process	1
regulation of transport	1
primary metabolic process	1
endocytosis	1
lipid metabolic process	1
catabolic process	1
intracellular anatomical structure	1
signal transduction	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
anion binding	1
molecular_function	1
binding	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1
brush border	1
apical plasma membrane	1

Protein interactions and networks

STRING

2248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLD2	NAPEPLD	Q6IQ20	919
PLD2	GPLD1	P80108	842
PLD2	ARF6	P26438	837
PLD2	ARF1	P10947	822
PLD2	DOCK2	Q92608	822
PLD2	SRC	P12931	777
PLD2	SDCBP	O00560	773
PLD2	RAC2	P15153	771
PLD2	RALA	P11233	743
PLD2	RPTOR	Q8N122	735
PLD2	PLD6	Q8N2A8	705
PLD2	PLD3	Q8IV08	665
PLD2	HCLS1	P14317	658
PLD2	CTTN	Q14247	653
PLD2	KCNK10	P57789	647

IntAct

125 interactions, top by confidence:

A	B	Type	Score
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
	PLD2	psi-mi:“MI:0915”(physical association)	0.770
PLD2		psi-mi:“MI:0915”(physical association)	0.770
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
PLD2	RAC2	psi-mi:“MI:0407”(direct interaction)	0.650
PLD2	RAC2	psi-mi:“MI:0915”(physical association)	0.650
GRB2	PLD2	psi-mi:“MI:0915”(physical association)	0.640
PLD2	GRB2	psi-mi:“MI:0915”(physical association)	0.640
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
TUBB	PLD2	psi-mi:“MI:0914”(association)	0.640
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
SPC24	PLD2	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
TUBA4A	TXNDC9	psi-mi:“MI:0914”(association)	0.640
PLD2		psi-mi:“MI:0915”(physical association)	0.590
	PLD2	psi-mi:“MI:0915”(physical association)	0.590
UNG	PLD2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (180): PLD2 (Affinity Capture-MS), PLD2 (Affinity Capture-MS), PLD2 (Affinity Capture-MS), PLD2 (Affinity Capture-MS), PLD2 (Affinity Capture-MS), PLD2 (Affinity Capture-MS), PLD2 (Affinity Capture-MS), PLD2 (Affinity Capture-MS), HIF1A (Affinity Capture-Western), PLD2 (Affinity Capture-Western), HIF1A (Reconstituted Complex), PLD2 (Affinity Capture-Western), EGLN1 (Affinity Capture-Western), PLD2 (Affinity Capture-Western), PLD2 (Reconstituted Complex)

ESM2 similar proteins: A4YTA9, A5EID1, A8IMV5, B3Q9Q6, B4S7P3, J9VTK7, O04865, O04883, O08684, O14939, O17405, O24308, O42938, O68984, O82549, P11035, P16638, P27783, P39863, P39867, P43101, P53396, P55939, P58766, P58991, P70496, P70498, P80581, P86387, P93400, P93844, P97813, Q00955, Q09706, Q13393, Q2IX63, Q32PF2, Q38882, Q41142, Q43007

Diamond homologs: O08684, O14939, P36126, P70496, P70498, P97813, Q09706, Q0V8L6, Q13393, Q54UK0, Q5BMR2, Q9LRZ5, Q9M9W8, Q9Z280, Q54Z25, O04865, O23078, O82549, P58766, P93400, P93733, Q38882, Q41142, Q43007, Q70EW5, Q9C888, Q9SSQ9, Q9T051, Q54WR4, P55939, Q9T052, Q9T053, P86387, P93844

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
PRKCA	up-regulates	PLD2	phosphorylation
JAK3	up-regulates	PLD2	phosphorylation
PRKCD	up-regulates	PLD2	phosphorylation
EGFR	“up-regulates activity”	PLD2	phosphorylation
P2RX7	up-regulates	PLD2
PLD2	up-regulates	ERK1/2
CDK5	“down-regulates activity”	PLD2	phosphorylation
CDK5	“up-regulates activity”	PLD2	phosphorylation
PTK2	“up-regulates activity”	PLD2	phosphorylation
GNAI1	down-regulates	PLD2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	20.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

187 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	145
Likely benign	7
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3610 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4807768:CTAGG:C	acceptor_loss	1.0000
17:4807770:A:AG	acceptor_gain	1.0000
17:4807770:A:AT	acceptor_loss	1.0000
17:4807770:AG:A	acceptor_gain	1.0000
17:4807771:G:GA	acceptor_gain	1.0000
17:4807771:GG:G	acceptor_gain	1.0000
17:4807771:GGAT:G	acceptor_gain	1.0000
17:4807866:G:GT	donor_gain	1.0000
17:4807869:G:GT	donor_gain	1.0000
17:4807879:CAG:C	donor_loss	1.0000
17:4807880:AGGTA:A	donor_loss	1.0000
17:4807881:GG:G	donor_loss	1.0000
17:4807882:GTAC:G	donor_loss	1.0000
17:4807891:G:GT	donor_gain	1.0000
17:4807891:G:T	donor_gain	1.0000
17:4807982:A:AG	acceptor_gain	1.0000
17:4807983:G:GG	acceptor_gain	1.0000
17:4807983:GCC:G	acceptor_gain	1.0000
17:4808134:G:GT	donor_gain	1.0000
17:4808135:G:T	donor_gain	1.0000
17:4808269:CCTAG:C	acceptor_loss	1.0000
17:4808270:CTAG:C	acceptor_loss	1.0000
17:4808271:TAGGT:T	acceptor_loss	1.0000
17:4808273:G:A	acceptor_loss	1.0000
17:4808393:GA:G	donor_gain	1.0000
17:4808413:CTCG:C	donor_loss	1.0000
17:4808415:CGG:C	donor_loss	1.0000
17:4808416:GG:G	donor_loss	1.0000
17:4808418:T:G	donor_loss	1.0000
17:4809292:C:G	acceptor_gain	1.0000

AlphaMissense

6069 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4818303:T:C	F643L	1.000
17:4818305:C:A	F643L	1.000
17:4818305:C:G	F643L	1.000
17:4819439:C:A	N773K	1.000
17:4819439:C:G	N773K	1.000
17:4808325:T:A	W98R	0.999
17:4808325:T:C	W98R	0.999
17:4808353:T:C	F107S	0.999
17:4814698:T:A	L387H	0.999
17:4814698:T:C	L387P	0.999
17:4815794:T:A	W439R	0.999
17:4815794:T:C	W439R	0.999
17:4815855:A:T	D459V	0.999
17:4816972:T:A	W540R	0.999
17:4816972:T:C	W540R	0.999
17:4817041:T:A	W563R	0.999
17:4817041:T:C	W563R	0.999
17:4818299:T:A	N641K	0.999
17:4818299:T:G	N641K	0.999
17:4818304:T:C	F643S	0.999
17:4818312:A:C	S646R	0.999
17:4818314:C:A	S646R	0.999
17:4818314:C:G	S646R	0.999
17:4819445:T:A	N775K	0.999
17:4819445:T:G	N775K	0.999
17:4819452:A:C	S778R	0.999
17:4819454:C:A	S778R	0.999
17:4819454:C:G	S778R	0.999
17:4808374:T:C	L114P	0.998
17:4809499:T:C	F188L	0.998

dbSNP variants (sampled 300 via entrez): RS1000158222 (17:4811763 G>A), RS1000190931 (17:4821123 C>A,T), RS1000257454 (17:4818935 G>A), RS1000375351 (17:4815764 G>A,T), RS1000521628 (17:4813787 A>G), RS1000626253 (17:4820934 G>A,C,T), RS1000760633 (17:4810578 G>C), RS1000926507 (17:4805255 CCGT>C), RS1001031469 (17:4822475 A>G,T), RS1001261062 (17:4813990 A>G), RS1001877975 (17:4809630 G>A,C), RS1002119902 (17:4816168 G>A,C), RS1002262641 (17:4821575 T>G), RS1002534858 (17:4816517 C>A,T), RS1002639041 (17:4805726 C>T)

Disease associations

OMIM: gene MIM:602384 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001413_9	Sphingolipid levels	1.000000e-09
GCST003155_22	Systemic lupus erythematosus	3.000000e-09
GCST003156_21	Systemic lupus erythematosus	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2734 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 78,474 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL81	RALOXIFENE	4	78,049
CHEMBL245621	HALOPEMIDE	2	425

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
FIPI	Inhibition	7.77	pIC50
VU0364739	Inhibition	7.7	pIC50
compound 69 [PMID: 19136975]	Inhibition	6.03	pIC50

Binding affinities (BindingDB)

149 measured of 150 human assays (183 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
cid_44573642	IC50	1 nM
N-[(2S)-1-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-1H-indole-2-carboxamide	IC50	1 nM
5-fluoranyl-N-[(2S)-1-[4-(2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-1H-indole-2-carboxamide	IC50	1 nM
cid_53470042	IC50	2 nM
N-[(2R)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]propan-2-yl]-1H-indole-2-carboxamide;2,2,2-trifluoroacetic acid	IC50	2 nM
VU0361535-1	IC50	2 nM
N-[(2S)-1-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-2-phenoxyacetamide;2,2,2-trifluoroacetic acid	IC50	2 nM
cid_53470207	IC50	2 nM
cid_44573690	IC50	3 nM
VU0404360-1	IC50	3 nM
N-[(2S)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]propan-2-yl]-3,4-difluorobenzamide;2,2,2-trifluoroacetic acid	IC50	3 nM
N-[(2S)-1-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]naphthalene-2-carboxamide;2,2,2-trifluoroacetic acid	IC50	3 nM
cid_44573687	IC50	4 nM
cid_21428895	IC50	4 nM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-chlorobenzamide;2,2,2-trifluoroacetic acid	IC50	4 nM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-fluorobenzamide;2,2,2-trifluoroacetic acid	IC50	4 nM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-3,4-difluorobenzamide;2,2,2-trifluoroacetic acid	IC50	4 nM
VU0359566-1	IC50	4 nM
4-chloro-N-[2-[4-(5-iodo-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]ethyl]benzamide;2,2,2-trifluoroacetic acid	IC50	5 nM
N-[(2S)-1-[1-[3,4-bis(fluoranyl)phenyl]-4-oxidanylidene-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]-5-fluoranyl-1H-indole-2-carboxamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	5 nM
3,4-bis(fluoranyl)-N-[(2S)-1-[4-(6-fluoranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	5 nM
4-chloranyl-N-[(2S)-1-[4-(5-chloranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	6 nM
N-[(2S)-3-methyl-1-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)butan-2-yl]-1H-indole-2-carboxamide;2,2,2-trifluoroacetic acid	IC50	7 nM
N-[(2S)-1-[4-(5-bromanyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-methyl-benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	7 nM
4-chloranyl-N-[(2S)-1-[4-(5-fluoranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	7 nM
VU0249424-1	IC50	7 nM
N-[(2S)-1-[4-(6-fluoranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-methyl-benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	8 nM
cid_21429000	IC50	9 nM
N-[2-[4-(5-iodo-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]ethyl]-2-phenyl-1-cyclopropanecarboxamide;2,2,2-trifluoroacetic acid	IC50	9 nM
N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]naphthalene-2-carboxamide;2,2,2-trifluoroacetic acid	IC50	10 nM
N-[(2S)-1-[4-(5-chloranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-fluoranyl-benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	10 nM
Halopemide	IC50	11 nM
N-[(2S)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-methylbenzamide;2,2,2-trifluoroacetic acid	IC50	11 nM
4-fluoro-N-[(2S)-1-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]propan-2-yl]benzamide;2,2,2-trifluoroacetic acid	IC50	11 nM
cid_44573689	IC50	12 nM
3,4-difluoro-N-[(2S)-1-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide;2,2,2-trifluoroacetic acid	IC50	12 nM
(1R,2R)-N-[(2S)-1-[4-(6-fluoranyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-2-phenyl-cyclopropane-1-carboxamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	12 nM
cis-(1R,2S)-N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-2-phenylcyclopropane-1-carboxamide	IC50	15 nM	US-9453017: Antiviral therapies with phospholipase D inhibitors
4-chloranyl-N-[(2S)-1-[4-(5-iodanyl-2-oxidanylidene-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	16 nM
N-[(2S)-1-[1-(3,4-difluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]quinoline-3-carboxamide;2,2,2-trifluoroacetic acid	IC50	16 nM
cid_53470346	IC50	16 nM
5-Fluoro-N-(2-(4-(2-Oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)ethyl)-1H-indole-2-carboxamide, 14	IC50	17 nM
N-[(2S)-1-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]quinoline-6-carboxamide	IC50	17 nM
cid_44573688	IC50	18 nM
cid_53470161	IC50	20 nM
[3H]4-OHT	IC50	21 nM
VU0409796-1	IC50	21 nM
cid_44573728	IC50	22 nM
3,4-dichloro-N-[(2S)-1-[4-(2-oxo-3H-benzimidazol-1-yl)-1-piperidinyl]propan-2-yl]benzamide;2,2,2-trifluoroacetic acid	IC50	23 nM
5-fluoranyl-N-[(2S)-3-methyl-1-(4-oxidanylidene-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)butan-2-yl]-1H-indole-2-carboxamide;2,2,2-tris(fluoranyl)ethanoic acid	IC50	26 nM

ChEMBL bioactivities

179 potent at pChembl≥5 of 186 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	IC50	2.5	nM	CHEMBL4475943
7.92	IC50	12	nM	CHEMBL4453586
7.85	IC50	14	nM	CHEMBL492972
7.82	IC50	15.15	nM	CHEMBL5555701
7.77	IC50	17	nM	CHEMBL398567
7.70	IC50	20	nM	CHEMBL2325485
7.70	IC50	20	nM	CHEMBL3925090
7.70	IC50	20	nM	CHEMBL4446255
7.70	IC50	20	nM	CHEMBL1254577
7.70	IC50	20	nM	CHEMBL398567
7.70	IC50	20	nM	CHEMBL246240
7.60	IC50	25	nM	CHEMBL1254736
7.58	IC50	26	nM	CHEMBL4594070
7.52	IC50	30	nM	CHEMBL471257
7.52	IC50	30	nM	CHEMBL1253900
7.46	IC50	35	nM	CHEMBL2325482
7.40	IC50	40	nM	CHEMBL1253820
7.38	IC50	42	nM	CHEMBL246032
7.38	IC50	42	nM	CHEMBL492971
7.37	IC50	43	nM	CHEMBL4436548
7.36	IC50	44	nM	CHEMBL2137046
7.30	IC50	50	nM	CHEMBL1254081
7.22	IC50	60	nM	CHEMBL3923136
7.22	IC50	60	nM	CHEMBL1254495
7.21	IC50	61	nM	CHEMBL523162
7.20	IC50	63	nM	CHEMBL1254653
7.19	IC50	64	nM	CHEMBL5085284
7.17	IC50	67	nM	CHEMBL4446255
7.16	IC50	70	nM	CHEMBL4515874
7.16	IC50	70	nM	CHEMBL1254823
7.16	IC50	70	nM	CHEMBL1254996
7.14	IC50	73	nM	CHEMBL1254908
7.12	IC50	76	nM	CHEMBL521990
7.10	IC50	79	nM	CHEMBL1213144
7.10	IC50	80	nM	CHEMBL1255082
7.08	IC50	84	nM	CHEMBL2325485
7.05	IC50	90	nM	CHEMBL471054
7.01	IC50	97	nM	CHEMBL492561
7.00	IC50	100	nM	CHEMBL3925090
7.00	IC50	100	nM	CHEMBL1255081
7.00	IC50	100	nM	CHEMBL1254176
6.96	IC50	110	nM	CHEMBL511475
6.94	IC50	115	nM	CHEMBL4570440
6.92	IC50	120	nM	CHEMBL2325487
6.92	IC50	120	nM	CHEMBL1254909
6.89	IC50	130	nM	CHEMBL1213097
6.89	IC50	130	nM	CHEMBL1213067
6.85	IC50	140	nM	CHEMBL4448918
6.85	IC50	140	nM	CHEMBL493010
6.85	IC50	140	nM	CHEMBL471056

PubChem BioAssay actives

208 with measured affinity, of 281 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[2-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0025	uM
N-[(2S)-1-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]-1H-indole-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0120	uM
3,4-difluoro-N-[2-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0140	uM
5-fluoro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-1H-indole-2-carboxamide	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.0150	uM
1-(4-methoxyphenyl)-3-phenylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.0150	uM
5-acetyl-N-[3,5-bis(trifluoromethyl)phenyl]-1H-indole-2-carboxamide	2073772: Inhibition of PLD2 (unknown origin)	ic50	0.0152	uM
N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-1H-indole-2-carboxamide	306650: Inhibition of PLD2	ic50	0.0200	uM
N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]naphthalene-2-carboxamide	1532921: Inhibition of PLD2 (unknown origin)	ic50	0.0200	uM
4-bromo-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	1532921: Inhibition of PLD2 (unknown origin)	ic50	0.0200	uM
4-bromo-N-[(2S)-1-[1-(3-methylphenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	729467: Inhibition of GFP-tagged PLD2 in human HEK293 cells assessed as deuterated 1-butanol incorporation pretreated for 5 mins prior to substrate addition measured after 30 mins by mass spectrometry	ic50	0.0200	uM
5-fluoro-N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0250	uM
N-[(2S)-1-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]naphthalene-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0260	uM
N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]-1-benzothiophene-2-carboxamide	349538: Inhibition of GFP-labeled PLD2 in human HEK293 cells	ic50	0.0300	uM
5-fluoro-N-[2-[1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0300	uM
4-fluoro-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	729467: Inhibition of GFP-tagged PLD2 in human HEK293 cells assessed as deuterated 1-butanol incorporation pretreated for 5 mins prior to substrate addition measured after 30 mins by mass spectrometry	ic50	0.0350	uM
N-[2-[1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]quinoline-3-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0400	uM
N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]quinoline-3-carboxamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0420	uM
4-chloro-N-[2-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0420	uM
N-[2-[(4R)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0430	uM
4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol	498478: Inhibition of GFP-tagged human PLD2 expressed in human HEK293 cells assessed as decrease in phosphatidylbutanol-[d9] production after 30 mins by mass spectrometric analysis	ic50	0.0440	uM
N-[2-[1-(4-chlorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-5-fluoro-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0500	uM
N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]naphthalene-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0600	uM
N-[2-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]quinoline-3-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0600	uM
4-chloro-N-[2-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0610	uM
N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]quinoline-3-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0630	uM
4-fluoro-N-[(2S)-1-[(5R)-5-(3-fluorophenyl)-2-oxo-1-oxa-3,9-diazaspiro[5.5]undecan-9-yl]propan-2-yl]benzamide	1827971: Inhibition of PLD2 (unknown origin) expressed in human HEK cells by immunoprecipitation	ic50	0.0640	uM
N-[2-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]-3-phenylprop-2-ynamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.0700	uM
N-[2-[1-(3-chlorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-4-fluorobenzamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0700	uM
N-[2-[1-(3,4-difluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]quinoline-3-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0700	uM
N-[2-[1-(3-chlorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-5-fluoro-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0730	uM
N-[2-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-4-fluorobenzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0760	uM
3,4,5-trimethoxy-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	498478: Inhibition of GFP-tagged human PLD2 expressed in human HEK293 cells assessed as decrease in phosphatidylbutanol-[d9] production after 30 mins by mass spectrometric analysis	ic50	0.0790	uM
N-[2-[1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]naphthalene-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.0800	uM
N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]quinoline-2-carboxamide	349538: Inhibition of GFP-labeled PLD2 in human HEK293 cells	ic50	0.0900	uM
N-[2-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-4-chlorobenzamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.0970	uM
N-[2-[1-(3,4-difluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-5-fluoro-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.1000	uM
N-[2-[1-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]-5-fluoro-1H-indole-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.1000	uM
N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]naphthalene-2-carboxamide	349538: Inhibition of GFP-labeled PLD2 in human HEK293 cells	ic50	0.1100	uM
N-[(2S)-1-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]quinoline-3-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.1150	uM
3-methyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.1200	uM
N-[2-[1-(3,4-difluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]naphthalene-2-carboxamide	515549: Inhibition of human GST-tagged PLD2A in human HEK293 cells	ic50	0.1200	uM
3,4-difluoro-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	729467: Inhibition of GFP-tagged PLD2 in human HEK293 cells assessed as deuterated 1-butanol incorporation pretreated for 5 mins prior to substrate addition measured after 30 mins by mass spectrometry	ic50	0.1200	uM
1-(4-methoxyphenyl)-3-naphthalen-1-ylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.1250	uM
4-chloro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	498482: Inhibition of human PLD2 assessed as release of methyl-[3H]choline from choline-methyl-[3H]dipalmitoylphosphatidylcholine after 30 mins by exogenous substrate assay	ic50	0.1300	uM
3,4-difluoro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	498478: Inhibition of GFP-tagged human PLD2 expressed in human HEK293 cells assessed as decrease in phosphatidylbutanol-[d9] production after 30 mins by mass spectrometric analysis	ic50	0.1300	uM
N-[(2S)-1-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl]naphthalene-2-carboxamide	349538: Inhibition of GFP-labeled PLD2 in human HEK293 cells	ic50	0.1400	uM
N-[2-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]naphthalene-2-carboxamide	418767: Inhibition of GFP-labelled human PLD2 HEK293 cells	ic50	0.1400	uM
N-[(2S)-1-[(4R)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]-1H-indole-2-carboxamide	1532925: Inhibition of GFP-fused PLD2 (unknown origin) expressed in HEK293 cells by cellular assay	ic50	0.1400	uM
1-tert-butyl-3-naphthalen-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.1500	uM
1-methyl-3-phenylpyrazolo[3,4-d]pyrimidin-4-amine	1800492: PLD In Vitro Kinetic Assay from Article 10.1111/cbdd.12319: “1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D.”	ic50	0.1500	uM

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Testosterone	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
1-Butanol	decreases reaction, increases activity, affects localization, affects reaction	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases abundance, decreases reaction, increases expression, increases reaction, increases activity	1
epigallocatechin gallate	increases reaction, decreases reaction, increases expression	1
phosphatidylbutanol	affects reaction, increases abundance, increases reaction	1
Go 6976	decreases reaction, increases expression, increases reaction	1
SB 203580	decreases reaction, increases expression, increases reaction	1
2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole	decreases reaction, increases expression, increases reaction	1
ilimaquinone	decreases reaction, increases activity	1
(N)-methanocarba-2MeSADP	affects reaction, increases phosphorylation	1
jinfukang	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetylcysteine	decreases reaction, increases expression, increases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases expression	1
beta-Endorphin	increases activity	1
Calcitriol	increases expression, affects cotreatment	1
Cholesterol	affects reaction, increases export, decreases reaction	1
Cisplatin	affects cotreatment, increases expression	1
Fentanyl	increases activity	1

ChEMBL screening assays

40 unique, capped per target: 36 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1220056	Binding	Inhibition of PLD2 mediated cancer cell migration in human MDA-231 cells at 200 nM by transwell invasion assay	Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. — Nat Chem Biol
CHEMBL1794370	Functional	PUBCHEM_BIOASSAY: Cellular PLD2 concentration response. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID588854]	PubChem BioAssay data set

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2B6	Abcam HeLa PLD2 KO	Cancer cell line	Female
CVCL_F1P6	HyCyte HCT 116 KO-hPLD2	Cancer cell line	Male
CVCL_TE44	HAP1 PLD2 (-) 1	Cancer cell line	Male
CVCL_TE45	HAP1 PLD2 (-) 2	Cancer cell line	Male
CVCL_TE46	HAP1 PLD2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.