PLD1

Summary

PLD1 (phospholipase D1, HGNC:9067) is a protein-coding gene on chromosome 3q26.31, encoding Phospholipase D1 (Q13393). Function as phospholipase selective for phosphatidylcholine.

This gene encodes a phosphatidylcholine-specific phospholipase which catalyzes the hydrolysis of phosphatidylcholine in order to yield phosphatidic acid and choline. The enzyme may play a role in signal transduction and subcellular trafficking. Alternative splicing results in multiple transcript variants with both catalytic and regulatory properties.

Source: NCBI Gene 5337 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PLD1-related congenital heart disease (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 395 total — 15 pathogenic, 12 likely-pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9067
Approved symbol	PLD1
Name	phospholipase D1
Location	3q26.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000075651
Ensembl biotype	protein_coding
OMIM	602382
Entrez	5337

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 14 protein_coding, 6 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000351298, ENST00000356327, ENST00000418087, ENST00000440204, ENST00000446289, ENST00000460926, ENST00000463281, ENST00000465816, ENST00000467432, ENST00000471075, ENST00000475273, ENST00000481505, ENST00000489995, ENST00000497307, ENST00000498278, ENST00000861047, ENST00000861048, ENST00000861049, ENST00000861050, ENST00000861051, ENST00000861052, ENST00000861053, ENST00000959554, ENST00000959555, ENST00000959556

RefSeq mRNA: 2 — MANE Select: NM_002662 NM_001130081, NM_002662

CCDS: CCDS3216, CCDS46957

Canonical transcript exons

ENST00000351298 — 27 exons

Exon	Start	End
ENSE00000446890	171688676	171688876
ENSE00000780377	171686685	171686798
ENSE00000780378	171687371	171687584
ENSE00000826235	171708755	171708838
ENSE00000826236	171709560	171709709
ENSE00001015327	171713893	171714045
ENSE00001791884	171600404	171603302
ENSE00001820986	171810399	171810483
ENSE00003460297	171677566	171677694
ENSE00003477151	171734865	171734970
ENSE00003495840	171620386	171620520
ENSE00003522841	171726018	171726076
ENSE00003553247	171676715	171676833
ENSE00003565148	171733444	171733509
ENSE00003573341	171692332	171692442
ENSE00003575848	171659213	171659301
ENSE00003597684	171735492	171735637
ENSE00003614968	171737532	171737659
ENSE00003619170	171605299	171605416
ENSE00003634040	171724696	171724788
ENSE00003641757	171644910	171645023
ENSE00003643036	171612279	171612432
ENSE00003646525	171662060	171662170
ENSE00003667546	171674500	171674613
ENSE00003678637	171642840	171642889
ENSE00003682124	171699745	171699826
ENSE00003687155	171737892	171738082

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 98.22.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5241 / max 128.4012, expressed in 753 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45608	13.6451	1667
45600	1.8445	493
45610	0.3678	111
203027	0.2145	93
45609	0.2090	88
45611	0.1155	50
45607	0.1048	38
45601	0.0806	34
45606	0.0726	22
45596	0.0338	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	98.22	gold quality
adrenal tissue	UBERON:0018303	94.98	gold quality
right adrenal gland cortex	UBERON:0035827	93.06	gold quality
esophagus mucosa	UBERON:0002469	92.52	gold quality
right adrenal gland	UBERON:0001233	92.36	gold quality
lower esophagus mucosa	UBERON:0035834	92.02	gold quality
duodenum	UBERON:0002114	91.95	gold quality
tongue squamous epithelium	UBERON:0006919	91.73	gold quality
left adrenal gland	UBERON:0001234	91.54	gold quality
corpus callosum	UBERON:0002336	91.33	gold quality
left adrenal gland cortex	UBERON:0035825	91.21	gold quality
adrenal gland	UBERON:0002369	91.17	gold quality
adrenal cortex	UBERON:0001235	91.09	gold quality
skin of abdomen	UBERON:0001416	90.77	gold quality
skin of leg	UBERON:0001511	90.64	gold quality
jejunal mucosa	UBERON:0000399	90.17	gold quality
left ovary	UBERON:0002119	90.09	gold quality
gingiva	UBERON:0001828	89.80	gold quality
gingival epithelium	UBERON:0001949	89.75	gold quality
zone of skin	UBERON:0000014	89.14	gold quality
epithelium of esophagus	UBERON:0001976	89.06	gold quality
secondary oocyte	CL:0000655	88.95	gold quality
colonic epithelium	UBERON:0000397	88.84	gold quality
esophagus squamous epithelium	UBERON:0006920	88.84	gold quality
mouth mucosa	UBERON:0003729	88.71	gold quality
squamous epithelium	UBERON:0006914	88.59	gold quality
rectum	UBERON:0001052	88.55	gold quality
minor salivary gland	UBERON:0001830	88.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.47	gold quality
skin of hip	UBERON:0001554	88.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	13.62
E-ANND-3	yes	8.57
E-MTAB-10596	no	185.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, CEBPA, CEBPB, CTNNB1, EWSR1, FLI1, NFATC2, NFKB, PGR, RXRA, SP1, TCF4, TCF7L2, VDR, ZHX2

miRNA regulators (miRDB)

109 targeting PLD1, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230

Literature-anchored findings (GeneRIF, showing 40)

• alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells (PMID:11821392)
• regulation of polymorphonuclear leukocyte degranulation and oxidant production (PMID:11830497)
• Detecting protein-phospholipid interactions. Epidermal growth factor-induced activation of phospholipase D1b in situ (PMID:11950840)
• binding of the Rho family member Cdc42 to PLD1 and the subsequent stimulation of its enzymatic activity are distinct events (PMID:12011045)
• PLD1 is threonine-phosphorylated in human-airway epithelial cells by a PKCdelta and src dependent mechanism (PMID:12014986)
• 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)
• activity regulated by actin in a polymerization-dependent, isoform-specific manner (PMID:12388543)
• activated by ADP-ribosylated RhoA (PMID:12593858)
• 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 D confers rapamycin resistance in human breast cancer cells. Elevated PLD activity in MCF-7 cells also caused rapamycin resistance for S6 kinase phosphorylation and serum-induced Myc expression. (PMID:12813467)
• protein kinase C alpha associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation-independent manner in melanoma cells, which contributes to the cell’s high invasive potential. (PMID:12839565)
• results indicate that PKCdelta inhibits TPA-induced PLD1 activation mediated by PKCalpha through the association with PLD1 (PMID:14596936)
• isoenzyme PLD1 is stimulated by phorbol ester and requires ADP-ribosylation factor, protein kinase C and Rho proteins for full activity (PMID:14646617)
• phospholipase D causes translocation of protein kinase C (PKC)betaII but not PKCbetaI to a juxtanuclear subset of recycling endosomes (PMID:15067001)
• phospholipase D isozymes mediate EGCG-induced COX-2 expression through PKC and p38 in immortalized astroglial line and normal astrocyte cells (PMID:15210717)
• PLD1 activity by regulating phosphatidic acid formation controls the early signals initiated by FcepsilonRI aggregation that lead to mast cell degranulation.PH (PMID:15339843)
• importance of phospholipase D in the oncogenic ability of Ras (PMID:15668389)
• phospholipase D suppresses protein phosphatase 2A and is involved in the mTOR survival pathway in the transformation of human cells (PMID:16109716)
• PLD1 is activated by exclusion from lipid rafts and that this activation conveys antiproliferative signals in lymphoid cells (PMID:16339545)
• 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)
• overexpression of PLD1 decreases, and down-presenilin 1, through its loop region, binds to phospholipase D1 (PLD1), thereby recruiting it to the Golgi/trans-Golgi network (PMID:16449386)
• adhesion stimulates PLD activity, and that PLD1 regulates the initial stages of phagocyte adhesion (PMID:16517737)
• endogenous PLD1 is a critical factor in the organization of the actin-based cytoskeleton, with regard to cell adhesion and migration (PMID:16608858)
• 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)
• demonstration of the involvement of PLD1 and PLD2 and its enzymatic activity toward chemokines in the key physiologic process of leukocyte migration (PMID:16873675)
• PLD1 may play a crucial role in collagen type I production through mTOR signaling in human dermal fibroblast. (PMID:16919239)
• We show that human PLD1b (hPLD1b) is an actin-binding protein and the N-terminus is predominantly involved in this interaction. (PMID:16978840)
• PLD1 regulates 8-Br-cAMP-induced decidualization through PLA2G1B, and PLD1 upregulation is essential for decidualization of endometrial stromal cells. (PMID:17065600)
• TNFalpha/CHX-induced cell death was significantly lowered in cells overexpressing PLD1 (PMID:17069807)
• isoform selective Arf/PLD interaction and not Arf/PtdIns4P5K will be the critical trigger in the formation of distinct, optimal triples of Arf/PLDs/PtdIns4P5Ks (PMID:17071135)
• Our results indicate a possible role for novel PKC isoforms in the regulation of P2X(7)-mediated PLD activity. (PMID:17130901)
• VDR and retinoid X receptor alpha (RXRalpha) binds to the VDRE and increases PLD1 gene expression in HaCaT cells. (PMID:17433303)
• 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)
• PLD control over expression of the Mac-1 activation epitope is critical for neutrophil migration to fMLP but not C5a. (PMID:17724165)
• PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas. (PMID:17726467)
• phospho-cofilin by its stimulatory effect on PLD1 may control a large variety of cellular functions. (PMID:17853892)
• These findings indicate the involvement of phospholipase D activation in hBD-2 up-regulation in gingival epithelial cells. (PMID:17986621)
• These results suggest that elevated expression and activity of PLD attenuate phorbol myristate acetate-induced Egr-1 expression via PI3K pathway. (PMID:18067864)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pld1a	ENSDARG00000056228
danio_rerio	pld1b	ENSDARG00000057125
mus_musculus	Pld1	ENSMUSG00000027695
rattus_norvegicus	Pld1	ENSRNOG00000028156
drosophila_melanogaster	Pld	FBGN0286511
caenorhabditis_elegans		WBGENE00004040

Paralogs (1): PLD2 (ENSG00000129219)

Protein

Protein identifiers

Phospholipase D1 — Q13393 (reviewed: Q13393)

Alternative names: Choline phosphatase 1, Phosphatidylcholine-hydrolyzing phospholipase D1

All UniProt accessions (4): Q13393, C9IY79, F8WBV7, H7C0L3

UniProt curated annotations — full annotation on UniProt →

Function. Function as phospholipase selective for phosphatidylcholine. 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.

Subunit / interactions. Interacts with PIP5K1B.

Subcellular location. Cytoplasm. Perinuclear region. Endoplasmic reticulum membrane. Golgi apparatus membrane. Late endosome membrane.

Tissue specificity. Expressed abundantly in the pancreas and heart and at high levels in brain, placenta, spleen, uterus and small intestine.

Disease relevance. Cardiac valvular dysplasia 1 (CVDP1) [MIM:212093] An autosomal recessive form of congenital heart defects, characterized by valvular malformations involving the pulmonic, tricuspid and mitral valves. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Stimulated by phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, activated by the phosphokinase C-alpha, by the ADP-ribosylation factor-1 (ARF-1), and to a lesser extent by GTP-binding proteins: RHO A, RAC-1 and CDC42. Inhibited by oleate.

Similarity. Belongs to the phospholipase D family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13393-1	PLD1A	yes
Q13393-2	PLD1B
Q13393-3	PLD1C
Q13393-4	PLD1D

RefSeq proteins (2): NP_001123553, NP_002653* (*=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: PF00169, 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)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PHOSPHATIDYLCHOLINE	0.0015–2.5	18
N-PALMITOYL-PHOSPHATIDYLETHANOLAMINE	0.0029–0.045	16
DIOLEOYL-PHOSPHATIDYLCHOLINE	0.0015–3	4
LYSOPHOSPHATIDYLCHOLINE	1–3	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
1,2-DIBUTYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.16	1
1-PALMITOYL-2-OLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.271	1
BIS(P-NITROPHENYL)PHOSPHATE	0.6	1
DIBUTYROYLPHOSPHATIDYLCHOLINE	0.2	1
DIHEPTANOYLPHOSPHATIDYLCHOLINE	0.23	1
DIHEXANOYLPHOSPHATIDYLCHOLINE	2.64	1
DIPALMITOYLPHOSPHATIDYLCHOLINE	0.78	1

Catalyzed reactions (Rhea), 3 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-sn-glycero-3-phosphate + choline + H(+) (RHEA:14445)
• ethanol + a 1,2-diacyl-sn-glycero-3-phosphocholine = 1,2-diacyl-sn-glycero-3-phosphoethanol + choline (RHEA:44868)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phosphate + choline + H(+) (RHEA:44872)

UniProt features (69 total): helix 22, strand 20, splice variant 5, sequence variant 5, turn 5, domain 4, modified residue 3, lipid moiety-binding region 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6U8Z	X-RAY DIFFRACTION	1.8
6OHR	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13393-F1	81.92	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 241, 499, 561, 629, 240

Function

Pathways and Gene Ontology

Reactome pathways

8 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-6798695	Neutrophil degranulation
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle

MSigDB gene sets: 379 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, BOYAULT_LIVER_CANCER_SUBCLASS_G56_DN, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, chr3q26, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_TRANSLATION

GO Biological Process (13): phosphatidic acid biosynthetic process (GO:0006654), chemotaxis (GO:0006935), small GTPase-mediated signal transduction (GO:0007264), Ras protein signal transduction (GO:0007265), phospholipid catabolic process (GO:0009395), cellular response to nutrient (GO:0031670), regulation of microvillus assembly (GO:0032534), positive regulation of translation (GO:0045727), regulation of vesicle-mediated transport (GO:0060627), regulation of synaptic vesicle cycle (GO:0098693), lipid metabolic process (GO:0006629), 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 (19): Golgi membrane (GO:0000139), lysosomal membrane (GO:0005765), endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), endocytic vesicle (GO:0030139), cytoplasmic vesicle (GO:0031410), late endosome membrane (GO:0031902), specific granule membrane (GO:0035579), perinuclear region of cytoplasm (GO:0048471), tertiary granule membrane (GO:0070821), cholinergic synapse (GO:0098981), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), organelle subcompartment (GO:0031984)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	4
Glycerophospholipid biosynthesis	2
Fcgamma receptor (FCGR) dependent phagocytosis	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
endomembrane system	3
intracellular anatomical structure	2
cytoplasmic vesicle	2
intracellular membrane-bounded organelle	2
secretory granule membrane	2
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
response to chemical	1
taxis	1
intracellular signaling cassette	1
small GTPase-mediated signal transduction	1
phospholipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
response to nutrient	1
cellular response to nutrient levels	1
cellular response to chemical stimulus	1
microvillus assembly	1
regulation of microvillus organization	1
regulation of plasma membrane bounded cell projection assembly	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
vesicle-mediated transport	1
regulation of cellular process	1
regulation of transport	1
regulation of vesicle-mediated transport	1
synaptic vesicle cycle	1
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
signal transduction	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
anion binding	1
molecular_function	1
binding	1

Protein interactions and networks

STRING

1964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLD1	GPLD1	P80108	841
PLD1	PEA15	Q15121	731
PLD1	PIK3C3	Q8NEB9	695
PLD1	PSEN1	P49768	692
PLD1	RALA	P11233	690
PLD1	RHEB	Q15382	676
PLD1	ARF6	P26438	674
PLD1	RAB3A	P20336	647
PLD1	RALB	P11234	647
PLD1	ARF1	P10947	610
PLD1	RHOA	P06749	608
PLD1	RAB8B	Q92930	603
PLD1	SNCAIP	Q9Y6H5	590
PLD1	SCAMP2	O15127	563
PLD1	PSENEN	Q9NZ42	549

IntAct

119 interactions, top by confidence:

A	B	Type	Score
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
OSBPL5	NAGLU	psi-mi:“MI:0914”(association)	0.640
ZRANB2	PIP4K2A	psi-mi:“MI:0914”(association)	0.610
PLD1	CFL1	psi-mi:“MI:0407”(direct interaction)	0.570
CFL1	PLD1	psi-mi:“MI:0915”(physical association)	0.570
CFL1	PLD1	psi-mi:“MI:0403”(colocalization)	0.570
PLD1	FANCG	psi-mi:“MI:0915”(physical association)	0.560
PLD1	TCF3	psi-mi:“MI:0915”(physical association)	0.560
PLD1	TP53BP1	psi-mi:“MI:0915”(physical association)	0.560
PLD1	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
PLD1	SPIRE1	psi-mi:“MI:0915”(physical association)	0.560
PLD1	SYNC	psi-mi:“MI:0915”(physical association)	0.560
PLD1	ASCL4	psi-mi:“MI:0915”(physical association)	0.560
PLD1	INCA1	psi-mi:“MI:0915”(physical association)	0.560
PLD1	LIAT1	psi-mi:“MI:0915”(physical association)	0.560
APP	PLD1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (199): PLD1 (Affinity Capture-Western), RHEB (Reconstituted Complex), PLD1 (Biochemical Activity), HIF1A (Affinity Capture-Western), HIF1A (Reconstituted Complex), PLD1 (Affinity Capture-Western), PLD1 (Reconstituted Complex), PLD1 (Affinity Capture-Western), PLD1 (Reconstituted Complex), VHL (Reconstituted Complex), EGLN1 (Affinity Capture-Western), PLD1 (Affinity Capture-MS), PLD1 (Affinity Capture-MS), PLD1 (Affinity Capture-MS), PLD1 (Affinity Capture-MS)

ESM2 similar proteins: C0LT23, D3YXJ0, E9PUQ8, F4JKI3, F4JQ95, G5EF51, O02697, O08684, O14829, O35655, P42336, P42338, P49621, P52429, P70496, Q13093, Q13393, Q16760, Q1PDI2, Q21029, Q28262, Q2TBM9, Q3SWT6, Q3U213, Q49MI3, Q56YN3, Q5JK52, Q5R6Y2, Q5XH30, Q60E60, Q62976, Q64398, Q6NS52, Q6USK2, Q7XQT2, Q7ZW00, Q80VJ4, Q86XP1, Q8BTI9, Q8C0L9

Diamond homologs: O04865, O04883, O23078, O82549, P55939, P58766, P70496, P86387, P93400, P93733, P93844, Q13393, Q38882, Q41142, Q43007, Q43270, Q70EW5, Q9C5Y0, Q9C888, Q9SSQ9, Q9T051, Q9T052, Q9T053, Q9Z280, O08684, O14939, P36126, P70498, P97813, Q09706, Q0V8L6, Q54UK0, Q5BMR2, Q9LRZ5, Q9M9W8, Q54Z25, A6QQP7, O75923, Q9ESD7, Q54WR4

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PRKAA2	up-regulates	PLD1	phosphorylation
RHEB	up-regulates	PLD1	binding
AMPK	up-regulates	PLD1	phosphorylation
PLD1	up-regulates	“phosphatidic acid”	“chemical modification”
PRKCA	up-regulates	PLD1	phosphorylation
RHOA	up-regulates	PLD1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	12
Uncertain significance	194
Likely benign	65
Benign	71

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1071285	NM_002662.5(PLD1):c.880A>T (p.Lys294Ter)	Pathogenic
1313339	NM_002662.5(PLD1):c.607-2A>C	Pathogenic
2042304	NM_002662.5(PLD1):c.1276_1279del (p.Ala426fs)	Pathogenic
2074815	NM_002662.5(PLD1):c.2416del (p.Ile805_Leu806insTer)	Pathogenic
2424512	NC_000003.11:g.(?171376983)(171410252_?)del	Pathogenic
2903572	NM_002662.5(PLD1):c.2178del (p.Ala727fs)	Pathogenic
3239271	NM_002662.5(PLD1):c.472C>T (p.Arg158Ter)	Pathogenic
3251798	NM_002662.5(PLD1):c.2034del (p.Trp678fs)	Pathogenic
4056489	NM_002662.5(PLD1):c.892C>T (p.Arg298Ter)	Pathogenic
426089	NM_002662.5(PLD1):c.1325A>C (p.His442Pro)	Pathogenic
426091	NM_002662.5(PLD1):c.2882+2T>C	Pathogenic
4748179	NM_002662.5(PLD1):c.1745del (p.Ser582fs)	Pathogenic
4775586	NM_002662.5(PLD1):c.2914G>T (p.Glu972Ter)	Pathogenic
4798150	NM_002662.5(PLD1):c.904_905del (p.Leu302fs)	Pathogenic
4812895	NM_002662.5(PLD1):c.665+1G>A	Pathogenic
1067422	NM_002662.5(PLD1):c.1753+1G>A	Likely pathogenic
1211263	NM_002662.5(PLD1):c.2681A>C (p.Tyr894Ser)	Likely pathogenic
1696830	NM_002662.5(PLD1):c.2023C>T (p.Arg675Trp)	Likely pathogenic
2441876	NM_002662.5(PLD1):c.2602C>T (p.Gln868Ter)	Likely pathogenic
2445423	NM_002662.5(PLD1):c.1062-2A>T	Likely pathogenic
2582520	NM_002662.5(PLD1):c.1403T>A (p.Val468Asp)	Likely pathogenic
3780441	NM_002662.5(PLD1):c.1061+1G>A	Likely pathogenic
3780442	NM_002662.5(PLD1):c.1708del (p.His570fs)	Likely pathogenic
426090	NM_002662.5(PLD1):c.1484_1485del (p.Thr495fs)	Likely pathogenic
4680876	NM_002662.5(PLD1):c.2338G>A (p.Glu780Lys)	Likely pathogenic
992859	NM_002662.5(PLD1):c.2083C>T (p.Arg695Cys)	Likely pathogenic
992976	NM_002662.5(PLD1):c.498del (p.Ser167fs)	Likely pathogenic

SpliceAI

5567 predictions. Top by Δscore:

Variant	Effect	Δscore
3:171603301:ACCTG:A	acceptor_loss	1.0000
3:171611502:A:AC	donor_gain	1.0000
3:171612274:CTGA:C	donor_loss	1.0000
3:171612275:TGA:T	donor_loss	1.0000
3:171612276:GACC:G	donor_loss	1.0000
3:171612277:A:AG	donor_loss	1.0000
3:171612278:C:T	donor_loss	1.0000
3:171612428:AGAGC:A	acceptor_gain	1.0000
3:171612429:GAGC:G	acceptor_gain	1.0000
3:171612430:AGC:A	acceptor_gain	1.0000
3:171612430:AGCC:A	acceptor_loss	1.0000
3:171612431:GC:G	acceptor_gain	1.0000
3:171612431:GCC:G	acceptor_loss	1.0000
3:171612432:CC:C	acceptor_gain	1.0000
3:171612432:CCTG:C	acceptor_loss	1.0000
3:171612433:C:CC	acceptor_gain	1.0000
3:171642834:A:AC	donor_gain	1.0000
3:171642834:ACTT:A	donor_loss	1.0000
3:171642835:C:CC	donor_gain	1.0000
3:171642835:CTT:C	donor_loss	1.0000
3:171642836:TTACG:T	donor_loss	1.0000
3:171642837:T:TG	donor_loss	1.0000
3:171642838:A:AC	donor_gain	1.0000
3:171642838:AC:A	donor_loss	1.0000
3:171642838:ACG:A	donor_gain	1.0000
3:171642838:ACGCT:A	donor_gain	1.0000
3:171642839:C:CA	donor_gain	1.0000
3:171642839:CG:C	donor_gain	1.0000
3:171642839:CGC:C	donor_gain	1.0000
3:171642839:CGCT:C	donor_gain	1.0000

AlphaMissense

7149 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:171612422:G:C	N913K	1.000
3:171612422:G:T	N913K	1.000
3:171662149:A:G	W751R	1.000
3:171662149:A:T	W751R	1.000
3:171676729:A:G	W701R	1.000
3:171676729:A:T	W701R	1.000
3:171676798:A:G	W678R	1.000
3:171676798:A:T	W678R	1.000
3:171676821:C:A	R670M	1.000
3:171677632:A:G	W644R	1.000
3:171677632:A:T	W644R	1.000
3:171688756:A:G	W487R	1.000
3:171688756:A:T	W487R	1.000
3:171688834:A:G	W461R	1.000
3:171688834:A:T	W461R	1.000
3:171708759:A:G	W381R	1.000
3:171708759:A:T	W381R	1.000
3:171603301:A:T	V1001D	0.999
3:171605340:A:G	W987R	0.999
3:171605340:A:T	W987R	0.999
3:171612384:T:A	E926V	0.999
3:171612386:A:C	S925R	0.999
3:171612386:A:T	S925R	0.999
3:171612388:T:G	S925R	0.999
3:171612407:G:C	S918R	0.999
3:171612407:G:T	S918R	0.999
3:171612409:T:G	S918R	0.999
3:171612412:G:T	R917S	0.999
3:171612416:A:C	N915K	0.999
3:171612416:A:T	N915K	0.999

dbSNP variants (sampled 300 via entrez): RS1000016274 (3:171748812 T>C,G), RS1000024940 (3:171640480 T>C), RS1000027283 (3:171771657 G>A,T), RS1000037097 (3:171696386 TAGG>T), RS1000067498 (3:171605241 GC>G), RS1000077274 (3:171605615 G>A), RS1000119416 (3:171658856 A>T), RS1000130189 (3:171690072 A>G), RS1000152096 (3:171734236 T>G), RS1000154370 (3:171696144 C>A,T), RS1000156267 (3:171740433 A>G), RS1000159754 (3:171778493 G>T), RS1000165499 (3:171708491 A>G), RS1000165877 (3:171795860 G>C), RS1000198600 (3:171708312 C>A)

Disease associations

OMIM: gene MIM:602382 | disease phenotypes: MIM:212093

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiac valvular defect, developmental	Definitive	Autosomal recessive
PLD1-related congenital heart disease	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
PLD1-related congenital heart disease	Definitive	AR

Mondo (2): cardiac valvular defect, developmental (MONDO:0008913), PLD1-related congenital heart disease (MONDO:1010144)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565882	Cardiac Valvular Defect, Developmental (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2536 (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 — Phosphatidylcholine-specific phospholipase D

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
FIPI	Inhibition	8.02	pIC50
compound 69 [PMID: 19136975]	Inhibition	7.34	pIC50

Binding affinities (BindingDB)

180 measured of 183 human assays (216 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
4-Methyl-N-(2-(4-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)ethyl)benzamide, 52	IC50	1.7 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

ChEMBL bioactivities

232 potent at pChembl≥5 of 239 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL4453586
9.00	IC50	1	nM	CHEMBL398567
8.70	IC50	2	nM	CHEMBL2304616
8.70	IC50	2	nM	CHEMBL493521
8.52	IC50	3	nM	CHEMBL492561
8.52	IC50	3	nM	CHEMBL492558
8.46	IC50	3.5	nM	CHEMBL492559
8.43	IC50	3.7	nM	CHEMBL3947795
8.43	IC50	3.7	nM	CHEMBL524182
8.40	IC50	4	nM	CHEMBL493010
8.40	IC50	4	nM	CHEMBL521990
8.40	IC50	4	nM	CHEMBL492972
8.40	IC50	4	nM	CHEMBL523011
8.26	IC50	5.5	nM	CHEMBL492704
8.22	IC50	6	nM	CHEMBL2325485
8.22	IC50	6	nM	CHEMBL3357311
8.22	IC50	6	nM	CHEMBL4446255
8.20	IC50	6.3	nM	CHEMBL1213097
8.19	IC50	6.4	nM	CHEMBL494145
8.15	IC50	7	nM	CHEMBL492971
8.13	IC50	7.4	nM	CHEMBL522488
8.10	IC50	8	nM	CHEMBL246032
8.10	IC50	8	nM	CHEMBL521677
8.05	IC50	8.9	nM	CHEMBL1213066
8.02	IC50	9.5	nM	CHEMBL398567
8.00	IC50	10	nM	CHEMBL494183
8.00	IC50	10	nM	CHEMBL492589
8.00	IC50	10	nM	CHEMBL1254495
7.96	IC50	11	nM	CHEMBL492588
7.96	IC50	11	nM	CHEMBL492572
7.92	IC50	12	nM	CHEMBL492369
7.92	IC50	12	nM	CHEMBL493736
7.85	IC50	14	nM	CHEMBL398568
7.82	IC50	15	nM	CHEMBL3947795
7.80	IC50	16	nM	CHEMBL4448918
7.80	IC50	16	nM	CHEMBL4514153
7.77	IC50	17	nM	CHEMBL3357312
7.77	IC50	17	nM	CHEMBL1213067
7.75	IC50	18	nM	CHEMBL3357310
7.75	IC50	18	nM	CHEMBL523162
7.72	IC50	19	nM	CHEMBL1213069
7.70	IC50	20	nM	CHEMBL2325482
7.70	IC50	20	nM	CHEMBL1213068
7.68	IC50	21	nM	CHEMBL3357315
7.68	IC50	21	nM	CHEMBL3357311
7.68	IC50	21	nM	CHEMBL492797
7.68	IC50	21	nM	HALOPEMIDE
7.68	IC50	21	nM	CHEMBL4475943
7.66	IC50	22	nM	CHEMBL5085284
7.66	IC50	22	nM	CHEMBL1213141

PubChem BioAssay actives

355 with measured affinity, of 428 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
5-fluoro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-1H-indole-2-carboxamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0010	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	1532924: Inhibition of PLD1 in human Calu1 cells	ic50	0.0010	uM
4-methyl-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	1799396: d.311 Enzymatic Inhibition Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ic50	0.0017	uM
N-[(2S)-1-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]naphthalene-2-carboxamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0020	uM
(2S)-N-[2-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-2-phenylcyclopropane-1-carboxamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0020	uM
N-[(2S)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-3,4-difluorobenzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0030	uM
N-[2-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-4-chlorobenzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0030	uM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-3,4-difluorobenzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0035	uM
trans-(1R,2R)-N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-2-phenylcyclopropane-1-carboxamide	1532920: Inhibition of PLD1 (unknown origin)	ic50	0.0037	uM
N-[2-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-4-fluorobenzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0040	uM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-chlorobenzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0040	uM
N-[2-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]naphthalene-2-carboxamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0040	uM
3,4-difluoro-N-[2-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0040	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	0.0050	uM
N-[(2S)-1-[4-(5-bromo-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]naphthalene-2-carboxamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0055	uM
N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propyl]-1H-indole-2-carboxamide	1174992: Inhibition of PLD2 (unknown origin) expressed in HEK293-gfp cells by cell-based assay	ic50	0.0060	uM
4-bromo-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	1532920: Inhibition of PLD1 (unknown origin)	ic50	0.0060	uM
4-bromo-N-[(2S)-1-[1-(3-methylphenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	729468: Inhibition of PLD1 in human Calu-1 cells assessed as deuterated 1-butanol incorporation pretreated for 5 mins prior to substrate addition measured after 30 mins by mass spectrometry	ic50	0.0060	uM
4-chloro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0063	uM
4-chloro-N-[(2S)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0064	uM
4-chloro-N-[2-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0070	uM
4-chloro-N-[(2S)-1-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0074	uM
N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]quinoline-3-carboxamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0080	uM
trans-(1R,2R)-N-[(2S)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-2-phenylcyclopropane-1-carboxamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0080	uM
4,5-dibromo-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]furan-2-carboxamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0089	uM
N-[2-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-4-methylbenzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0100	uM
N-[(2S)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-4-fluorobenzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0100	uM
N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]naphthalene-2-carboxamide	515548: Inhibition of PLD1 in human calu1 cells	ic50	0.0100	uM
N-[(2S)-1-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]naphthalene-2-carboxamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0110	uM
4-fluoro-N-[(2S)-1-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]benzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0110	uM
N-[2-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-4-fluorobenzamide	1799396: d.311 Enzymatic Inhibition Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ic50	0.0110	uM
trans-(1R,2R)-N-[(2S)-1-[4-(6-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propan-2-yl]-2-phenylcyclopropane-1-carboxamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0120	uM
4-fluoro-N-[2-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0120	uM
N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-1-benzothiophene-2-carboxamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0140	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	1532924: Inhibition of PLD1 in human Calu1 cells	ic50	0.0160	uM
N-[(2S)-1-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]propan-2-yl]-3-phenylprop-2-ynamide	1532924: Inhibition of PLD1 in human Calu1 cells	ic50	0.0160	uM
3,4-difluoro-N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propyl]benzamide	1174992: Inhibition of PLD2 (unknown origin) expressed in HEK293-gfp cells by cell-based assay	ic50	0.0170	uM
3,4-difluoro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0170	uM
5-fluoro-N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propyl]-1H-indole-2-carboxamide	1174992: Inhibition of PLD2 (unknown origin) expressed in HEK293-gfp cells by cell-based assay	ic50	0.0180	uM
4-chloro-N-[2-[4-(5-fluoro-2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	418766: Inhibition of human PLD1 in Calu1 cells	ic50	0.0180	uM
3,4-dichloro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0190	uM
9-oxo-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]fluorene-4-carboxamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0200	uM
4-fluoro-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide	729468: Inhibition of PLD1 in human Calu-1 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
1-methyl-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	0.0200	uM
3,4-difluoro-N-[2-[3-fluoro-4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]benzamide	1174991: Inhibition of PLD1 (unknown origin) expressed in human Calu1 cells by cell-based assay	ic50	0.0210	uM
N-[2-[(4S)-4-(4-fluorophenyl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl]ethyl]-1H-indole-2-carboxamide	1532924: Inhibition of PLD1 in human Calu1 cells	ic50	0.0210	uM
N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]naphthalene-2-carboxamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0210	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	1827970: Inhibition of PLD1 (unknown origin) expressed in human HEK cells by immunoprecipitation assay	ic50	0.0220	uM
N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]furan-2-carboxamide	1799397: Calu-1 Cell-Based Assay from Article 10.1038/nchembio.140: “Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.”	ec50	0.0220	uM
N-[(2S)-1-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl]naphthalene-2-carboxamide	349537: Inhibition of PLD1 in human Calu1 cells	ic50	0.0250	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
sodium arsenite	increases abundance, decreases expression, affects cotreatment	4
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	4
bisphenol A	decreases expression, increases expression, increases methylation	3
Smoke	decreases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Tretinoin	increases expression	3
trichostatin A	increases expression	2
epigallocatechin gallate	increases expression, increases reaction, affects cotreatment, decreases expression	2
perfluoro-n-nonanoic acid	decreases expression, increases expression	2
Resveratrol	affects cotreatment, increases expression, decreases activity, increases activity, increases localization	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Hydrogen Peroxide	decreases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	decreases expression	2
Tobacco Smoke Pollution	decreases expression, decreases reaction, increases expression, increases phosphorylation, affects reaction (+1 more)	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
sotorasib	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	increases expression, increases reaction, increases activity, increases abundance, affects reaction (+1 more)	1
ethylene dichloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
oxophenylarsine	decreases reaction, increases expression, increases phosphorylation	1
hydroquinone	decreases expression	1
muconaldehyde	decreases expression	1

ChEMBL screening assays

33 unique, capped per target: 29 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1220060	Binding	Inhibition of PLD1 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
CHEMBL1794331	Functional	PUBCHEM_BIOASSAY: Cellular PLD1 concentration response. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID588854]	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1YG	Abcam A-549 PLD1 KO	Cancer cell line	Male
CVCL_D2CM	Abcam HCT 116 PLD1 KO	Cancer cell line	Male
CVCL_TE42	HAP1 PLD1 (-) 1	Cancer cell line	Male
CVCL_TE43	HAP1 PLD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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