PLA2G7

Summary

PLA2G7 (phospholipase A2 group VII, HGNC:9040) is a protein-coding gene on chromosome 6p12.3, encoding Platelet-activating factor acetylhydrolase (Q13093). Lipoprotein-associated calcium-independent phospholipase A2 involved in phospholipid catabolism during inflammatory and oxidative stress response.

The protein encoded by this gene is a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. Defects in this gene are a cause of platelet-activating factor acetylhydrolase deficiency. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 7941 — RefSeq curated summary.

At a glance

• Gene–disease (curated): platelet-activating factor acetylhydrolase deficiency (Limited, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 117 total — 3 likely-pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005084

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9040
Approved symbol	PLA2G7
Name	phospholipase A2 group VII
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Aliases	PAFAH, LDL-PLA2, Lp-PLA2
Ensembl gene	ENSG00000146070
Ensembl biotype	protein_coding
OMIM	601690
Entrez	7941

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000274793, ENST00000537365, ENST00000878321, ENST00000878322, ENST00000960372

RefSeq mRNA: 2 — MANE Select: NM_005084 NM_001168357, NM_005084

CCDS: CCDS4917

Canonical transcript exons

ENST00000274793 — 12 exons

Exon	Start	End
ENSE00000973734	46722783	46722925
ENSE00000973737	46716384	46716528
ENSE00000973739	46712269	46712337
ENSE00000973740	46711496	46711619
ENSE00000973741	46710545	46710658
ENSE00000973742	46709327	46709418
ENSE00000973743	46707991	46708161
ENSE00000973744	46705153	46705301
ENSE00001139724	46735180	46735375
ENSE00001176697	46704201	46704696
ENSE00003518608	46714460	46714553
ENSE00003569297	46716975	46717096

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 96.41.

FANTOM5 (CAGE): breadth broad, TPM avg 23.8374 / max 1041.2175, expressed in 535 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73856	21.0565	511
73855	2.6160	236
73857	0.1649	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	96.41	gold quality
decidua	UBERON:0002450	94.18	gold quality
vermiform appendix	UBERON:0001154	87.95	gold quality
monocyte	CL:0000576	86.67	gold quality
mononuclear cell	CL:0000842	86.41	gold quality
leukocyte	CL:0000738	85.84	gold quality
lymph node	UBERON:0000029	85.44	gold quality
spleen	UBERON:0002106	85.41	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.30	gold quality
placenta	UBERON:0001987	82.76	gold quality
rectum	UBERON:0001052	81.33	gold quality
endometrium	UBERON:0001295	81.01	gold quality
caecum	UBERON:0001153	79.45	gold quality
palpebral conjunctiva	UBERON:0001812	79.42	gold quality
thyroid gland	UBERON:0002046	78.38	gold quality
left lobe of thyroid gland	UBERON:0001120	77.94	gold quality
visceral pleura	UBERON:0002401	77.14	gold quality
islet of Langerhans	UBERON:0000006	77.05	gold quality
colonic mucosa	UBERON:0000317	76.60	gold quality
gall bladder	UBERON:0002110	76.59	gold quality
trabecular bone tissue	UBERON:0002483	76.36	gold quality
right lobe of thyroid gland	UBERON:0001119	76.29	gold quality
upper leg skin	UBERON:0004262	75.99	gold quality
granulocyte	CL:0000094	74.92	gold quality
right lung	UBERON:0002167	74.38	gold quality
prostate gland	UBERON:0002367	74.30	gold quality
epithelium of nasopharynx	UBERON:0001951	74.21	silver quality
nasopharynx	UBERON:0001728	74.20	silver quality
superficial temporal artery	UBERON:0001614	74.14	gold quality
upper lobe of left lung	UBERON:0008952	73.19	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	457.27
E-MTAB-6701	yes	44.36
E-CURD-112	yes	19.53
E-ANND-3	yes	7.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MECP2, NFE2L3

miRNA regulators (miRDB)

18 targeting PLA2G7, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-630	97.50	66.38	921
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-4509	96.19	65.80	900

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of hPLA2G7 by adenoviral gene transfer in mice diminished the neointima formation (restenosis) induced by a wire-guided denudation of endothelium of the common left carotid and spontaneous atherosclerosis in aortic roots. (PMID:11369691)
• The genetic mutation of plasma PAF-AH gene appear to be an independent risk factor for AAA (abdominal aortic aneurysm) (PMID:11807372)
• the ratio of HDL-associated PAF-AH-total plasma enzyme activity may be useful as a potential marker of atherogenicity in subjects with primary hypercholesterolemia. (PMID:11861667)
• electrotransfer of the human plasma PAF-AH gene to skeletal muscle reduces the extent of atherosclerosis in apoE(-/-) mice (PMID:12428682)
• role as oxidized phospholipid hydrolase of high density lipoprotein particles (PMID:12466264)
• colony-stimulating factors may modulate the local concentration of platelet-activating factor in the decidua via their inhibitory or stimulatory effect on the secretion of platelet-activating factor acetylhydrolase (PMID:12548211)
• Human plasma PAF-AH exerts an antiatherogenic effect by binding to all the lipoproteins and thereby protecting them from oxidation, producing less proatherogenic lipoproteins and preserving HDL functions. (PMID:12649088)
• This genotype is not major determinant of population genetic risk of coronary heart disease(CHD), but association of this genotype with low levels of Lp-PLA(2) strongly support pro-inflammatory causative, and not consequential, role of Lp-PLA(2) in CHD. (PMID:12801611)
• Platelet-activating factor inhibits PAF-AH secretion by decidual macrophages.Inhibitory action is mediated by signal transduction involving intracellular calcium and protein kinase C. (PMID:14671207)
• The PAF-AH gene missense mutation has no relation to either susceptibility or severity of conventional multiple sclerosis, yet its activity is down-regulated, and it may confer the severity of female opticospinal-MS. (PMID:15081260)
• Ala379 substitution to Val in PLA2G7 was less frequent in CAD patients than in controls, was associated with a lower risk of future CAD and showed higher plasma activity, thus Val379 may be protective against development of CAD. (PMID:15115767)
• mutations InsA191 and I317N impair function of the Lp-PLA2 gene in lipoprotein-associated phospholipase A2 deficiency patients (PMID:15148590)
• the mechanism by which LPS modulates expression of PAF AH at the transcriptional level (PMID:15215249)
• OxLDL accumulates in arteries in nonhyperlipidemic transgenic animals within 1 week after injury and local expression of human PAFAH reduces this accumulation and exerts antiinflammatory, antithrombotic, and antiproliferative effects (PMID:15956136)
• The findings show that the 994(G–> T) mutation of plasma PAF-AH gene may be an independent risk for atherosclerotic cerebral infarction, but not for lacunar infarction. (PMID:16086290)
• lipoprotein-associated phospholipase A(2) activity, but not the enzyme mass, is a marker of small, dense LDL in human plasma (PMID:16223884)
• PAF acetylhydrolases play key roles in the hydrolysis of F2-isoprostanes esterified on phospholipids in vivo (PMID:16371369)
• Lp-PLA2 activity and PLA2G7 A379V genotype were related to mediators of atherosclerosis in a diabetic study. (PMID:16438975)
• Lipoprotein-associated phospholipase A(2) (Lp-PLA(2))is strongly correlated with several cardiovascular risk factors. (PMID:16530769)
• PON1 is neither a PLOOH peroxidase nor hydrolase and that the phospholipase A(2)-like activity previously attributed to PON1 in natural enzyme preparations was actually due to novel PLOOH hydrolytic activity of contaminating PAF-AH (PMID:17090529)
• COX-2 and PAF-AH play a role in the occurrence of MODS (PMID:17092424)
• Lipoprotein-associated phospholipase A2 A379V variant is associated with body composition changes in response to exercise training. (PMID:17174223)
• The distribution of platelet-activating factor acetylhydrolase (PAF-AH) was associated with paroxysmal atrial fibrillation (AF) and may be a marker of inflammation in patients with paroxysmal AF. (PMID:17251670)
• Early coronary atherosclerosis in humans is characterized by local production of Lp-PLA2. Local coronary production of lysophosphatidylcholine, the active product of Lp-PLA2, is associated with endothelial dysfunction. (PMID:17502572)
• The increased values of VEGF, PLA2-LDL and P-selectin in patients with long standing pulmonary hypertension are related to severe endothelial dysfunction and may have prognostic values. (PMID:17509958)
• LDL-C level showed a significant interaction with the G994T genotype in Japanese (PMID:17587752)
• inactivation of PAF, produced by TEC, by the overexpression of plasma PAF-AH affects survival, migration, and the angiogenic response of TEC both in vitro and in vivo (PMID:17908960)
• PAF-AcH could play an anti-inflammatory role by reducing the concentration of PAF. (PMID:17981297)
• We described two new highly polymorphic markers located 31 bp downstream of the last nucleotide of exon 12 in the 3’ UTR region of the gene PLA2G7 (PMID:18001304)
• Race and sex independently influence Lp-PLA2 activity and mass (PMID:18061193)
• Lp-PLA2 may have different mechanisms of action among American and Japanese men. Lp-PLA2 levels can not explain the observed CAC differences between the two populations. (PMID:18094516)
• Electrospray ionization mass spectrometry identifies substrates and products of lipoprotein-associated phospholipase A2 in oxidized human low density lipoprotein (PMID:18165686)
• Elevated levels of Lp-PLA(2)(lipoprotein-associated phospholipase A2) activity and mass, respectively, were in this study, independently of established risk factors related to the incidence of ischemic stroke (PMID:18201705)
• PLA2G7 represents an important, potentially functional candidate in the pathophysiology of coronary artery disease based on replicated associations using two independent datasets and multiple statistical approaches. (PMID:18204052)
• Lp-PLA(2) was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA(2) (PMID:18259035)
• These findings strongly support a role for Lp-PLA2 in the pathophysiology and clinical presentation of cerebrovascular disease. (PMID:18356547)
• association of Lp-PLA(2) levels with arterial disease events implies a role for this enzyme in atherogenesis, our findings suggest that it is not prothrombotic. (PMID:18383322)
• Lp-PLA2 is independently associated with progression of cardiac allograft vasculopathy and predicts a higher incidence of cardiovascular events and cardiovascular death in transplant patients (PMID:18408575)
• The aim of the present study was to evaluate the contribution of the PAFAH gene Arg92His, Ile198Thr and Ala379Val polymorphisms to resistance toward developing cardiovascular events in healthy Sicilian octogenarians. (PMID:18431085)
• mouse and human PAF-AHs associate with human HDL particles of different density (PMID:18434304)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pla2g7	ENSDARG00000003584
mus_musculus	Pla2g7	ENSMUSG00000023913
rattus_norvegicus	Pla2g7	ENSRNOG00000025691
caenorhabditis_elegans	paf-1	WBGENE00003906
caenorhabditis_elegans		WBGENE00003907

Paralogs (1): PAFAH2 (ENSG00000158006)

Protein

Protein identifiers

Platelet-activating factor acetylhydrolase — Q13093 (reviewed: Q13093)

Alternative names: 1-alkyl-2-acetylglycerophosphocholine esterase, 2-acetyl-1-alkylglycerophosphocholine esterase, Group-VIIA phospholipase A2, LDL-associated phospholipase A2, PAF 2-acylhydrolase

All UniProt accessions (1): Q13093

UniProt curated annotations — full annotation on UniProt →

Function. Lipoprotein-associated calcium-independent phospholipase A2 involved in phospholipid catabolism during inflammatory and oxidative stress response. At the lipid-aqueous interface, hydrolyzes the ester bond of fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity). Specifically targets phospholipids with a short-chain fatty acyl group at sn-2 position. Can hydrolyze phospholipids with long fatty acyl chains, only if they carry oxidized functional groups. Hydrolyzes and inactivates platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a potent pro-inflammatory signaling lipid that acts through PTAFR on various innate immune cells. Hydrolyzes oxidatively truncated phospholipids carrying an aldehyde group at omega position, preventing their accumulation in low-density lipoprotein (LDL) particles and uncontrolled pro-inflammatory effects. As part of high-density lipoprotein (HDL) particles, can hydrolyze phospholipids having long-chain fatty acyl hydroperoxides at sn-2 position and protect against potential accumulation of these oxylipins in the vascular wall. Catalyzes the release from membrane phospholipids of F2-isoprostanes, lipid biomarkers of cellular oxidative damage.

Subcellular location. Secreted. Extracellular space.

Tissue specificity. Plasma. Secreted by macrophages (at protein level).

Post-translational modifications. N-glycosylated. Macrophage-derived PLA2G7 carries sialylated complex-type N-glycans that hinder its binding to HDL particles.

Disease relevance. Platelet-activating factor acetylhydrolase deficiency (PAFAD) [MIM:614278] An enzymatic deficiency that results in exacerbated bodily response to inflammatory agents. It can be associated with several disease states including inflammatory gastrointestinal disorders, asthma and atopy. Asthmatic individuals with PAFAD may manifest aggravated respiratory symptoms. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated upon monocyte differentiation toward macrophage lineage.

Similarity. Belongs to the AB hydrolase superfamily. Lipase family.

RefSeq proteins (2): NP_001161829, NP_005075* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016715	PAF_acetylhydro_eukaryote	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF03403

Enzyme classification (BRENDA):

• EC 3.1.1.4 — phospholipase A2 (BRENDA: 129 organisms, 452 substrates, 710 inhibitors, 90 Km, 14 kcat entries)
• EC 3.1.1.47 — 1-alkyl-2-acetylglycerophosphocholine esterase (BRENDA: 15 organisms, 161 substrates, 92 inhibitors, 50 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
1-O-ALKYL-2-ACETYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0052–0.392	18
PHOSPHATIDYLCHOLINE	0.05–17	12
1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.94–13.85	7
PHOSPHATIDYLETHANOLAMINE	0.02–10.5	5
ACETYLATED PLATELET-ACTIVATION FACTOR	0.082–0.206	4
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOPHORYLCHOLINE	1.12–5.13	3
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	3–3.92	3
1,2-DIOCTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.12–3.2	3
1-HEXADECYL-2-ACETYL-SN-GLYCEROL-3-PHOSPHOCHOLIN	0.0137–0.0142	2
1-PALMITOYL-2-ARACHIDONYLPHOSPHATIDYLCHOLINE	0.0016–0.0033	2
LECITHIN	8.3–8.5	2
1-PALMITOYL-2-(5-OXOVALEROYL)-SN-GLYCERO-3-PHOSP	0.0193–0.0431	2
F2-ISOPROSTANE-PHOSPHOCHOLINE	—	2
(3E)-3-[(3AS,7AS)-3-METHYL-2-OXO-6-(PROPAN-2-YLI	0.742	1
(3R,3AS,5AS,8BR)-3,5A,5B-TRIMETHYL-3A,4,5,5A,5B,	0.746	1

Catalyzed reactions (Rhea), 12 shown:

• a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-sn-glycero-3-phosphocholine + acetate + H(+) (RHEA:17777)
• 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+) (RHEA:40479)
• 1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine + H2O = 5-oxopentanoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:40483)
• 1-hexadecanoyl-2-[9-hydroperoxy-(10E-octadecenoyl)]-sn-glycero-3-phosphocholine + H2O = 9-hydroperoxy-10E-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41151)
• 1-hexadecanoyl-2-(10-hydroperoxy-8E-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 10-hydroperoxy-(8E)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41155)
• 1-hexadecanoyl-2-glutaroyl-sn-glycero-3-phosphocholine + H2O = glutarate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41159)
• 1-hexadecanoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine + H2O = 9-oxononanoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41179)
• 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-octadecyl-sn-glycero-3-phosphocholine + acetate + H(+) (RHEA:41183)
• 1-hexadecanoyl-2-propionyl-sn-glycero-3-phosphocholine + H2O = propanoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41191)
• 1-hexadecanoyl-2-butanoyl-sn-glycero-3-phosphocholine + H2O = butanoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41195)
• 1-hexadecanoyl-2-pentanoyl-sn-glycero-3-phosphocholine + H2O = pentanoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41199)
• 1-hexadecanoyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + acetate + H(+) (RHEA:41203)

UniProt features (65 total): mutagenesis site 18, helix 16, strand 15, sequence variant 7, active site 3, turn 2, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3D59	X-RAY DIFFRACTION	1.5
3F97	X-RAY DIFFRACTION	1.7
3F98	X-RAY DIFFRACTION	1.7
5YEA	X-RAY DIFFRACTION	1.8
5YE8	X-RAY DIFFRACTION	1.85
5YE9	X-RAY DIFFRACTION	1.88
5LP1	X-RAY DIFFRACTION	1.91
5JAU	X-RAY DIFFRACTION	1.95
5JAT	X-RAY DIFFRACTION	2.04
5JAD	X-RAY DIFFRACTION	2.05
5LZ5	X-RAY DIFFRACTION	2.05
5JAH	X-RAY DIFFRACTION	2.06
5JAL	X-RAY DIFFRACTION	2.06
5JAO	X-RAY DIFFRACTION	2.06
5JAS	X-RAY DIFFRACTION	2.06
5LZ9	X-RAY DIFFRACTION	2.06
5LZ4	X-RAY DIFFRACTION	2.07
3D5E	X-RAY DIFFRACTION	2.1
3F96	X-RAY DIFFRACTION	2.1
5LZ2	X-RAY DIFFRACTION	2.1
5LZ7	X-RAY DIFFRACTION	2.1
6M06	X-RAY DIFFRACTION	2.1
5JAR	X-RAY DIFFRACTION	2.11
5LZ8	X-RAY DIFFRACTION	2.11
5JAN	X-RAY DIFFRACTION	2.12
5LYY	X-RAY DIFFRACTION	2.17
6M08	X-RAY DIFFRACTION	2.19
3F9C	X-RAY DIFFRACTION	2.3
5YE7	X-RAY DIFFRACTION	2.31
5I8P	X-RAY DIFFRACTION	2.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13093-F1	87.94	0.79

Functional residue map

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

Catalytic / active sites (3): 273 (nucleophile); 296 (charge relay system); 351 (charge relay system)

Glycosylation sites (2): 423, 433

Mutagenesis-validated functional residues (18):

Position	Phenotype
108	activity is higher than wild-type.
114	impairs the association with ldl particles.
115	impairs the association with ldl particles.
116	reduces the association with ldl particles.
117	reduces the association with ldl particles.
205	impairs the association with ldl particles.
273	loss of activity.
286	almost no activity.
286	diminishes activity.
296	loss of activity.
304	no change in activity.
338	activity is higher than wild-type.
351	loss of activity.
367	reduces the association with hdl particles.
368	impairs the association with hdl particles.
369	impairs the association with hdl particles.
370	reduces the association with hdl particles.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-422085	Synthesis, secretion, and deacylation of Ghrelin

MSigDB gene sets: 272 (showing top): MODULE_172, GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CERVERA_SDHB_TARGETS_1_DN, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_GLYCEROLIPID_METABOLIC_PROCESS

GO Biological Process (12): peptide hormone processing (GO:0016486), low-density lipoprotein particle remodeling (GO:0034374), lipid oxidation (GO:0034440), plasma lipoprotein particle oxidation (GO:0034441), phosphatidylcholine catabolic process (GO:0034638), platelet activating factor metabolic process (GO:0046469), positive regulation of inflammatory response (GO:0050729), platelet activating factor catabolic process (GO:0062234), positive regulation of monocyte chemotaxis (GO:0090026), lipid metabolic process (GO:0006629), phospholipid catabolic process (GO:0009395), lipid catabolic process (GO:0016042)

GO Molecular Function (6): 1-alkyl-2-acetylglycerophosphocholine esterase activity (GO:0003847), phospholipid binding (GO:0005543), hydrolase activity, acting on ester bonds (GO:0016788), obsolete calcium-independent phospholipase A2 activity (GO:0047499), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): extracellular region (GO:0005576), low-density lipoprotein particle (GO:0034362), high-density lipoprotein particle (GO:0034364), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Peptide hormone metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma lipoprotein particle remodeling	2
glycerophospholipid catabolic process	2
plasma lipoprotein particle	2
hormone metabolic process	1
signaling receptor ligand precursor processing	1
lipid modification	1
phosphatidylcholine metabolic process	1
glycerophospholipid metabolic process	1
ether lipid metabolic process	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
glycerol ether catabolic process	1
platelet activating factor metabolic process	1
monocyte chemotaxis	1
positive regulation of leukocyte chemotaxis	1
positive regulation of mononuclear cell migration	1
regulation of monocyte chemotaxis	1
primary metabolic process	1
phospholipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
lipid metabolic process	1
catabolic process	1
carboxylic ester hydrolase activity	1
lipid binding	1
hydrolase activity	1
binding	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G7	APOB	P04114	784
PLA2G7	APOA1	P02647	742
PLA2G7	PON1	P27169	719
PLA2G7	LPCAT2	Q7L5N7	719
PLA2G7	CRP	P02741	715
PLA2G7	PLA2G2A	P14555	712
PLA2G7	KCNMB1	P78475	679
PLA2G7	APOE	P02649	677
PLA2G7	PLA2G10	O15496	663
PLA2G7	MPO	P05164	628
PLA2G7	PLA2G4A	P47712	624
PLA2G7	APOA2	P02652	619
PLA2G7	PLA2G15	Q8NCC3	612
PLA2G7	CEACAM4	O75871	601
PLA2G7	PLA2G1B	P04054	579

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
PLA2G7	PTPRN	psi-mi:“MI:0915”(physical association)	0.560
PLA2G7	TUBA3C	psi-mi:“MI:0914”(association)	0.350
PLA2G7	metE	psi-mi:“MI:0915”(physical association)	0.000
fadH	PLA2G7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): PTPRN (Affinity Capture-MS), PTPRN (Affinity Capture-MS), PTPRN (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), PDXP (Affinity Capture-MS)

ESM2 similar proteins: A2A7Z8, A7LB60, P08910, P0DKC5, P0DKC6, P22760, P70683, P83006, Q05AK6, Q0P5B7, Q13093, Q14032, Q1LZ86, Q28017, Q32LS6, Q4R2Y9, Q4V8A1, Q502J0, Q5EA42, Q5PPS7, Q5VUY0, Q5VUY2, Q5XI64, Q5ZJL8, Q5ZKL5, Q60963, Q63276, Q6DHN0, Q6GLL2, Q6IE26, Q6P093, Q7L211, Q7M370, Q7SY73, Q7Z5M8, Q802V6, Q80UX8, Q8BM81, Q8IUS5, Q8R2Y0

Diamond homologs: P70683, P79106, P83006, Q13093, Q22943, Q28017, Q28262, Q60963, Q8VDG7, Q90678, Q99487

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NFE2L3	“up-regulates quantity by expression”	PLA2G7	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	80
Likely benign	21
Benign	6

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1028854	NM_005084.4(PLA2G7):c.470+1G>A	Likely pathogenic
3065950	NM_005084.4(PLA2G7):c.109+2T>C	Likely pathogenic
3384855	NM_005084.4(PLA2G7):c.664-2A>G	Likely pathogenic

SpliceAI

1488 predictions. Top by Δscore:

Variant	Effect	Δscore
6:46705299:CCC:C	acceptor_gain	1.0000
6:46705300:CCC:C	acceptor_gain	1.0000
6:46710540:CTTA:C	donor_loss	1.0000
6:46710541:TTA:T	donor_loss	1.0000
6:46710543:A:AC	donor_gain	1.0000
6:46710544:C:CC	donor_gain	1.0000
6:46710668:T:C	acceptor_gain	1.0000
6:46710668:T:TC	acceptor_gain	1.0000
6:46710671:T:C	acceptor_gain	1.0000
6:46710671:T:TC	acceptor_gain	1.0000
6:46735173:T:TA	donor_gain	1.0000
6:46735178:A:AC	donor_gain	1.0000
6:46735179:C:CC	donor_gain	1.0000
6:46735179:CT:C	donor_gain	1.0000
6:46705300:CC:C	acceptor_gain	0.9900
6:46705301:CC:C	acceptor_gain	0.9900
6:46708172:T:C	acceptor_gain	0.9900
6:46710656:TACC:T	acceptor_loss	0.9900
6:46710657:ACC:A	acceptor_loss	0.9900
6:46710658:CCTAA:C	acceptor_gain	0.9900
6:46710662:A:AC	acceptor_gain	0.9900
6:46710662:A:C	acceptor_gain	0.9900
6:46710664:A:AC	acceptor_gain	0.9900
6:46717092:CCATG:C	acceptor_gain	0.9900
6:46717093:CATGC:C	acceptor_gain	0.9900
6:46722941:T:TC	acceptor_gain	0.9900
6:46735182:AGG:A	donor_gain	0.9900
6:46705302:C:CC	acceptor_gain	0.9800
6:46705302:CTAAA:C	acceptor_loss	0.9800
6:46708172:T:TC	acceptor_gain	0.9800

AlphaMissense

2934 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:46709379:A:G	S273P	0.992
6:46710647:T:A	R225S	0.985
6:46710647:T:G	R225S	0.985
6:46704639:A:G	L416P	0.983
6:46705169:G:C	F391L	0.983
6:46705169:G:T	F391L	0.983
6:46705171:A:G	F391L	0.983
6:46712275:T:A	E178V	0.982
6:46716471:A:G	W97R	0.982
6:46716471:A:T	W97R	0.982
6:46716515:C:G	R82P	0.980
6:46705276:C:G	D356H	0.979
6:46712308:A:G	L167P	0.979
6:46709372:C:T	G275D	0.978
6:46712287:A:T	V174D	0.978
6:46714482:A:G	S150P	0.978
6:46709384:C:T	G271E	0.977
6:46705291:G:C	H351D	0.976
6:46709372:C:A	G275V	0.976
6:46710648:C:G	R225T	0.975
6:46708065:G:C	F322L	0.974
6:46708065:G:T	F322L	0.974
6:46708067:A:G	F322L	0.974
6:46712305:G:T	A168E	0.974
6:46708145:C:G	D296H	0.972
6:46712271:G:C	H179Q	0.972
6:46712271:G:T	H179Q	0.972
6:46711603:C:G	A186P	0.971
6:46712284:G:T	A175D	0.971
6:46709374:A:C	F274L	0.970

dbSNP variants (sampled 300 via entrez): RS1000012755 (6:46706609 C>G,T), RS1000046564 (6:46720047 G>A), RS1000266270 (6:46726166 C>A,T), RS1000306509 (6:46732323 T>C), RS1000505492 (6:46719327 A>C,T), RS1000554568 (6:46715951 A>G), RS1000906452 (6:46716141 A>G), RS1000917276 (6:46733703 G>A,T), RS1000958966 (6:46723787 T>G), RS1001027369 (6:46721712 C>A,T), RS1001219913 (6:46705591 AC>A), RS1001267548 (6:46713349 G>A), RS1001307316 (6:46717776 A>C,G), RS1001585446 (6:46734230 G>A), RS1001724230 (6:46718744 G>A)

Disease associations

OMIM: gene MIM:601690 | disease phenotypes: MIM:614278

GenCC curated gene-disease

Disease	Classification	Inheritance
platelet-activating factor acetylhydrolase deficiency	Limited	Autosomal recessive

Mondo (1): platelet-activating factor acetylhydrolase deficiency (MONDO:0013663)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0040175	Platelet-activating factor acetylhydrolase deficiency
HP:0040178	Increased level of platelet-activating factor

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000671_3	Lipoprotein-associated phospholipase A2 activity and mass	6.000000e-14
GCST001273_5	Lipoprotein-associated phospholipase A2 activity and mass	2.000000e-23
GCST001273_6	Lipoprotein-associated phospholipase A2 activity and mass	1.000000e-10
GCST001727_5	Lipoprotein-associated phospholipase A2 activity and mass	3.000000e-19
GCST004963_14	Lipoprotein phospholipase A2 activity in cardiovascular disease	1.000000e-178
GCST004966_2	Lipoprotein-associated phospholipase A2 activity change in response to darapladib treatment in cardiovascular disease	8.000000e-47
GCST006585_630	Blood protein levels	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0008395	response to darapladib
EFO:0008432	lipoprotein-associated phospholipase A(2) change measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566640	Platelet-Activating Factor Acetylhydrolase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3514 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,799 (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
CHEMBL175247	ORLISTAT	4	38,186
CHEMBL204021	DARAPLADIB	3	370
CHEMBL2104981	RILAPLADIB	2	218
CHEMBL3634561	GSK-2647544	1	25

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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
darapladib	Inhibition	10.31	pIC50
rilapladib	Competitive	9.64	pIC50
compound 37 [PMID: 29193967]	Inhibition	7.85	pIC50
(S)-23 [PMID: 27933945]	Inhibition	6.92	pIC50
ABX-1431	Inhibition	5.0	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL1946067	IC50	88 nM

ChEMBL bioactivities

500 potent at pChembl≥5 of 532 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	CHEMBL10921
10.31	IC50	0.049	nM	DARAPLADIB
10.22	IC50	0.06	nM	CHEMBL10921
10.20	IC50	0.0631	nM	DARAPLADIB
10.00	IC50	0.1	nM	CHEMBL87729
10.00	IC50	0.1	nM	DARAPLADIB
10.00	IC50	0.1	nM	CHEMBL10441
10.00	IC50	0.1	nM	CHEMBL89451
9.96	Ki	0.11	nM	DARAPLADIB
9.92	IC50	0.12	nM	CHEMBL407553
9.92	IC50	0.12	nM	CHEMBL87100
9.85	IC50	0.14	nM	CHEMBL2380965
9.77	IC50	0.17	nM	CHEMBL314768
9.70	IC50	0.2	nM	CHEMBL79555
9.70	IC50	0.2	nM	CHEMBL85080
9.70	IC50	0.2	nM	CHEMBL84894
9.70	IC50	0.2	nM	CHEMBL87787
9.70	IC50	0.2	nM	CHEMBL87156
9.70	IC50	0.2	nM	CHEMBL315504
9.70	IC50	0.2	nM	CHEMBL314954
9.70	IC50	0.2	nM	CHEMBL348243
9.70	IC50	0.2	nM	CHEMBL150446
9.64	IC50	0.23	nM	CHEMBL2380967
9.62	IC50	0.24	nM	CHEMBL2380954
9.60	IC50	0.25	nM	CHEMBL10501
9.60	IC50	0.25	nM	DARAPLADIB
9.60	IC50	0.2512	nM	RILAPLADIB
9.52	IC50	0.3	nM	CHEMBL85885
9.52	IC50	0.3	nM	CHEMBL85179
9.52	IC50	0.3	nM	CHEMBL328527
9.46	IC50	0.35	nM	CHEMBL315766
9.40	IC50	0.4	nM	CHEMBL2111560
9.40	IC50	0.4	nM	CHEMBL421165
9.40	IC50	0.4	nM	CHEMBL10604
9.40	IC50	0.4	nM	CHEMBL10663
9.40	IC50	0.3981	nM	CHEMBL3967156
9.40	IC50	0.4	nM	CHEMBL293933
9.34	IC50	0.46	nM	CHEMBL2380957
9.30	IC50	0.5	nM	CHEMBL10759
9.30	IC50	0.5	nM	CHEMBL87355
9.30	IC50	0.5	nM	CHEMBL262376
9.30	IC50	0.5	nM	CHEMBL358483
9.30	IC50	0.5	nM	CHEMBL155227
9.30	IC50	0.5	nM	CHEMBL153546
9.26	IC50	0.55	nM	CHEMBL2380968
9.22	IC50	0.6	nM	DARAPLADIB
9.22	IC50	0.6	nM	CHEMBL329158
9.22	IC50	0.6	nM	CHEMBL276856
9.22	IC50	0.6	nM	CHEMBL415274
9.22	IC50	0.6	nM	CHEMBL153164

PubChem BioAssay actives

503 with measured affinity, of 1343 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-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	<0.0001	uM
N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	1308811: Inhibition of human recombinant Lp-PLA2 using 2-thio-PAF as substrate after 20 mins by CPM-based fluorescence assay	ic50	<0.0001	uM
N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5,6,7,8-tetrahydroquinazolin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	103814: Inhibitory activity against recombinant human Lp-PLA2	ic50	0.0001	uM
N-decyl-4-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5-(pyrimidin-5-ylmethyl)pyrimidin-1-yl]butanamide	103816: Inhibition of lipoprotein associated phospholipase A2 in human plasma	ic50	0.0001	uM
2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-(2-morpholin-4-yl-2-oxoethyl)-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0001	uM
N-[2-(ethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0001	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-[ethyl(2-hydroxyethyl)amino]ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0001	uM
1-[[5-[[2-(dimethylamino)ethyl-methylamino]methyl]-4-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-2-[(4-fluorophenyl)methylsulfanyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one	746823: Inhibition of recombinant human Lp-PLA2 using [3H]PAF as substrate at 10 nM incubated for 5 mins prior to substrate addition measured after 10 mins by liquid scintillation counting analysis	ic50	0.0001	uM
2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-(2-piperidin-1-ylethyl)-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(2-methoxypyrimidin-5-yl)methyl]-4-oxopyrimidin-1-yl]-N-methylacetamide	103815: Inhibitory activity against recombinant human Lp-PLA2 (Lp-PLA2).	ic50	0.0002	uM
2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(2-methoxypyrimidin-5-yl)methyl]-4-oxopyrimidin-1-yl]-N-methyl-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	103815: Inhibitory activity against recombinant human Lp-PLA2 (Lp-PLA2).	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(2-methoxypyrimidin-5-yl)methyl]-4-oxopyrimidin-1-yl]-N-(2-hydroxyethyl)acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-(dimethylamino)-2-oxoethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(2-methoxypyrimidin-5-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-(dimethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(2-methoxypyrimidin-5-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-[di(propan-2-yl)amino]ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-(ethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-(dimethylamino)-2-oxoethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5-[(2-piperazin-1-ylpyrimidin-5-yl)methyl]pyrimidin-1-yl]-N-methylacetamide	103815: Inhibitory activity against recombinant human Lp-PLA2 (Lp-PLA2).	ic50	0.0002	uM
2-[(4-fluorophenyl)methylsulfanyl]-1-[[5-[[methyl(2-pyrrolidin-1-ylethyl)amino]methyl]-4-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one	746823: Inhibition of recombinant human Lp-PLA2 using [3H]PAF as substrate at 10 nM incubated for 5 mins prior to substrate addition measured after 10 mins by liquid scintillation counting analysis	ic50	0.0002	uM
1-[[5-[1-[2-(diethylamino)ethyl-methylamino]ethyl]-4-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-2-[(4-fluorophenyl)methylsulfanyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one	746823: Inhibition of recombinant human Lp-PLA2 using [3H]PAF as substrate at 10 nM incubated for 5 mins prior to substrate addition measured after 10 mins by liquid scintillation counting analysis	ic50	0.0002	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5,6,7,8-tetrahydroquinazolin-1-yl]acetamide	103814: Inhibitory activity against recombinant human Lp-PLA2	ic50	0.0003	uM
N-dodecyl-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5-(pyrimidin-5-ylmethyl)pyrimidin-1-yl]acetamide	103816: Inhibition of lipoprotein associated phospholipase A2 in human plasma	ic50	0.0003	uM
N-[2-(dimethylamino)-2-oxoethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0003	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[3-(diethylamino)propyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0003	uM
2-[2-[(2,3-difluorophenyl)methylsulfanyl]-4-oxoquinolin-1-yl]-N-[1-(2-methoxyethyl)piperidin-4-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	1331349: Inhibition of LpPLA2 (unknown origin)	ic50	0.0003	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-(2-piperidin-1-ylethyl)acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0003	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-1-yl]acetamide	103814: Inhibitory activity against recombinant human Lp-PLA2	ic50	0.0004	uM
4-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5-(pyrimidin-5-ylmethyl)pyrimidin-1-yl]-N-[(E)-octadec-9-enyl]butanamide	158953: Inhibitory activity against human lipoprotein associated phospholipase A2 (Lp-PLA2)	ic50	0.0004	uM
N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-1-yl]-N-[[3-[4-(trifluoromethyl)phenyl]-1-bicyclo[1.1.1]pentanyl]methyl]acetamide	1331350: Inhibition of human recombinant LpPLA2	ic50	0.0004	uM
4-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5-(pyrimidin-5-ylmethyl)pyrimidin-1-yl]-N-octylbutanamide	103816: Inhibition of lipoprotein associated phospholipase A2 in human plasma	ic50	0.0004	uM
4-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5-(pyrimidin-5-ylmethyl)pyrimidin-1-yl]-N-[(Z)-octadec-9-enyl]butanamide	103816: Inhibition of lipoprotein associated phospholipase A2 in human plasma	ic50	0.0004	uM
N-[2-(diethylamino)ethyl]-2-[5-ethyl-2-[(4-fluorophenyl)methylsulfanyl]-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	103814: Inhibitory activity against recombinant human Lp-PLA2	ic50	0.0004	uM
N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5,6-dimethyl-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	103814: Inhibitory activity against recombinant human Lp-PLA2	ic50	0.0005	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(2-methoxypyrimidin-5-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	103815: Inhibitory activity against recombinant human Lp-PLA2 (Lp-PLA2).	ic50	0.0005	uM
N-[2-[bis(2-hydroxyethyl)amino]ethyl]-N-[[4-(4-chlorophenyl)phenyl]methyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0005	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[3-(dimethylamino)propyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0005	uM
N-[[4-(4-bromophenyl)phenyl]methyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-methylacetamide	103815: Inhibitory activity against recombinant human Lp-PLA2 (Lp-PLA2).	ic50	0.0005	uM
1-[[5-[4-(diethylamino)butyl]-4-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-2-[(4-fluorophenyl)methylsulfanyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one	746823: Inhibition of recombinant human Lp-PLA2 using [3H]PAF as substrate at 10 nM incubated for 5 mins prior to substrate addition measured after 10 mins by liquid scintillation counting analysis	ic50	0.0005	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-2-[5-[(1-ethyl-2-oxopyrimidin-5-yl)methyl]-2-[(4-fluorophenyl)methylsulfanyl]-4-oxopyrimidin-1-yl]-N-methylacetamide	103815: Inhibitory activity against recombinant human Lp-PLA2 (Lp-PLA2).	ic50	0.0005	uM
2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(2-methoxypyrimidin-5-yl)methyl]-4-oxopyrimidin-1-yl]-N-[[4-(4-fluorophenyl)phenyl]methyl]-N-methylacetamide	103815: Inhibitory activity against recombinant human Lp-PLA2 (Lp-PLA2).	ic50	0.0006	uM
2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-(2-hydroxyethyl)-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0006	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-(2-hydroxyethyl)acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0006	uM
1-[[5-[[3-(dimethylamino)propyl-methylamino]methyl]-4-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-2-[(4-fluorophenyl)methylsulfanyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one	746823: Inhibition of recombinant human Lp-PLA2 using [3H]PAF as substrate at 10 nM incubated for 5 mins prior to substrate addition measured after 10 mins by liquid scintillation counting analysis	ic50	0.0006	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-(dimethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0006	uM
N-[2-(dimethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0007	uM
N-[[4-(4-chlorophenyl)phenyl]methyl]-N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]acetamide	159113: Inhibitory concentration against Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) was estimated	ic50	0.0007	uM
2-[(4-fluorophenyl)methylsulfanyl]-1-[[5-[[methyl(2-piperidin-1-ylethyl)amino]methyl]-4-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-1,2,4-triazol-3-yl]methyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one	746823: Inhibition of recombinant human Lp-PLA2 using [3H]PAF as substrate at 10 nM incubated for 5 mins prior to substrate addition measured after 10 mins by liquid scintillation counting analysis	ic50	0.0007	uM
2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-methyl-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	103815: Inhibitory activity against recombinant human Lp-PLA2 (Lp-PLA2).	ic50	0.0007	uM
N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-5-propylpyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	103814: Inhibitory activity against recombinant human Lp-PLA2	ic50	0.0008	uM
N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-methylsulfanyl-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide	103814: Inhibitory activity against recombinant human Lp-PLA2	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
trichostatin A	affects cotreatment, increases expression	3
Orlistat	affects cotreatment, decreases activity	3
SB 203580	decreases reaction, increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Ozone	affects expression, increases abundance, increases expression	2
tungsten carbide	affects cotreatment, decreases expression	1
urushiol	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
terbufos	increases methylation	1
sodium bichromate	decreases expression	1
1,6-bis(cyclohexyloximinocarbonyl)hexane	decreases activity	1
pentanal	increases expression	1
bepafant	decreases reaction, increases expression	1
BN 50739	increases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases expression, increases reaction	1
acyline	increases expression	1
lipopolysaccharide, Escherichia coli O111 B4	decreases reaction, affects cotreatment, increases expression, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	decreases expression, affects binding	1
Ezetimibe	affects cotreatment, decreases activity	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, decreases expression	1
Arsenicals	decreases expression	1
Benzene	increases expression	1

ChEMBL screening assays

129 unique, capped per target: 122 binding, 7 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032505	Binding	Effect on human plasma LDL-PLA2 activity by LS-3B fluorescence spectrometry	Specific antioxidant activity of caffeoyl derivatives and other natural phenolic compounds: LDL protection against oxidation and decrease in the proinflammatory lysophosphatidylcholine production. — J Nat Prod
CHEMBL2114765	Functional	PubChem BioAssay. Late stage assay provider results from the probe development effort to identify inhibitors of plasma platelet activating factor acetylhydrolase (pPAFAH): fluorescence-based dose response biochemical gel-based competitive A	PubChem BioAssay data set

Clinical trials (associated diseases)

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