PLA2G5

Summary

PLA2G5 (phospholipase A2 group V, HGNC:9038) is a protein-coding gene on chromosome 1p36.13, encoding Phospholipase A2 group V (P39877). Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids.

This gene is a member of the secretory phospholipase A2 family. It is located in a tightly-linked cluster of secretory phospholipase A2 genes on chromosome 1. The encoded enzyme catalyzes the hydrolysis of membrane phospholipids to generate lysophospholipids and free fatty acids including arachidonic acid. It preferentially hydrolyzes linoleoyl-containing phosphatidylcholine substrates. Secretion of this enzyme is thought to induce inflammatory responses in neighboring cells. Alternatively spliced transcript variants have been found, but their full-length nature has not been determined.

Source: NCBI Gene 5322 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial benign flecked retina (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 136 total — 1 pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000929

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9038
Approved symbol	PLA2G5
Name	phospholipase A2 group V
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000127472
Ensembl biotype	protein_coding
OMIM	601192
Entrez	5322

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 49 protein_coding, 7 protein_coding_CDS_not_defined

ENST00000375108, ENST00000460175, ENST00000465698, ENST00000469069, ENST00000478803, ENST00000486277, ENST00000489871, ENST00000498348, ENST00000894073, ENST00000894074, ENST00000894075, ENST00000894076, ENST00000894077, ENST00000894078, ENST00000894079, ENST00000894080, ENST00000894081, ENST00000894082, ENST00000894083, ENST00000894084, ENST00000894085, ENST00000894086, ENST00000894087, ENST00000894088, ENST00000894089, ENST00000894090, ENST00000894091, ENST00000894092, ENST00000894093, ENST00000894094, ENST00000894095, ENST00000894096, ENST00000962155, ENST00000962156, ENST00000962157, ENST00000962158, ENST00000962159, ENST00000962160, ENST00000962161, ENST00000962162, ENST00000962163, ENST00000962164, ENST00000962165, ENST00000962166, ENST00000962167, ENST00000962168, ENST00000962169, ENST00000962170, ENST00000962171, ENST00000962172, ENST00000962173, ENST00000962174, ENST00000962175, ENST00000962176, ENST00000962177, ENST00000962178

RefSeq mRNA: 1 — MANE Select: NM_000929 NM_000929

CCDS: CCDS202

Canonical transcript exons

ENST00000375108 — 5 exons

Exon	Start	End
ENSE00001465779	20070194	20070465
ENSE00001543290	20090568	20091911
ENSE00003546908	20089789	20089895
ENSE00003636962	20084821	20084870
ENSE00003685741	20086083	20086227

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 98.28.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0023 / max 138.7210, expressed in 211 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1096	0.4824	166
1093	0.1929	22
1092	0.1039	36
1099	0.0884	50
1098	0.0457	19
1097	0.0364	12
1095	0.0338	10
1094	0.0188	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	98.28	gold quality
apex of heart	UBERON:0002098	98.05	gold quality
cardiac atrium	UBERON:0002081	97.87	gold quality
right coronary artery	UBERON:0001625	96.39	gold quality
heart left ventricle	UBERON:0002084	96.29	gold quality
cardiac ventricle	UBERON:0002082	96.12	gold quality
left ovary	UBERON:0002119	95.86	gold quality
heart	UBERON:0000948	95.71	gold quality
right ovary	UBERON:0002118	95.03	gold quality
coronary artery	UBERON:0001621	94.88	gold quality
left coronary artery	UBERON:0001626	94.86	gold quality
heart right ventricle	UBERON:0002080	93.16	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.60	gold quality
myocardium	UBERON:0002349	91.51	gold quality
pigmented layer of retina	UBERON:0001782	89.98	gold quality
left ventricle myocardium	UBERON:0006566	89.56	gold quality
ovary	UBERON:0000992	87.09	gold quality
choroid plexus epithelium	UBERON:0003911	87.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.58	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.45	gold quality
lower esophagus	UBERON:0013473	84.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.89	gold quality
right testis	UBERON:0004534	82.19	gold quality
left testis	UBERON:0004533	81.46	gold quality
diaphragm	UBERON:0001103	81.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.18	gold quality
putamen	UBERON:0001874	81.00	gold quality
vena cava	UBERON:0004087	80.79	silver quality
thoracic aorta	UBERON:0001515	80.47	gold quality
ascending aorta	UBERON:0001496	80.35	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	731.35
E-MTAB-7316	yes	20.34
E-GEOD-135922	yes	14.48
E-GEOD-134144	yes	11.10
E-MTAB-11268	no	2566.39
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting PLA2G5, 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-4533	100.00	69.48	2758
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-6893-3P	97.79	64.91	1238

Literature-anchored findings (GeneRIF, showing 28)

• circulating human neutrophils express groups V and X sPLA(2) (GV and GX sPLA(2)) mRNA and contain GV and GX sPLA(2) proteins, whereas GIB, GIIA, GIID, GIIE, GIIF, GIII, and GXII sPLA(2)s are undetectable (PMID:11741884)
• PLA2G5 binds to PLA2G4 to induce leukotriene synthesis in neutrophils (PMID:12124392)
• stimulation of three isoforms of PLA2 by thapsigargin liberates free AA that, in turn, induces capacitative calcium influx in human T-cells (PMID:12423354)
• group V phospholipase A2 induces group IVA phospholipase A2-independent cysteinyl leukotriene synthesis in human eosinophils (PMID:12796497)
• sPLA2-V expression in hepatocytes is induced by viral infection, fibrosis, and circulatory disturbance. Immunostaining using sPLA2-V antibody is useful for the detection of injured hepatocytes in patients with liver diseases. (PMID:15377291)
• foam cell formation is promoted by a SR-A- and CD36-independent process that involves cellular proteoglycans and Group V secretory phospholipase A2-modified low density lipoprotein (PMID:16040605)
• Group V sPLA2 was expressed in ischaemic cardiomyocytes around the lesion, while no expression was observed in normal heart. (PMID:16115226)
• present results raise the possibility that group V and X sPLA2s may play a role in innate immunity against adenoviral infection in the respiratory tract (PMID:16146426)
• group V PLA2 released from neighboring cells may function in triggering the activation of inflammatory cells under physiological conditions (PMID:16476735)
• Group V phospholipase A2, endogenously secreted from activated epithelial cells, promotes secretion of leukotriene C4 from cocultured eosinophils. (PMID:16785555)
• PLA2G5 tSNP haplotypes demonstrate an association with total and LDL cholesterol and oxLDL/LDL. (PMID:17545304)
• Group V phospholipase A2 mediates barrier disruption of human pulmonary endothelial cells caused by LPS in vitro (PMID:20448053)
• The effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, were examined. (PMID:22041135)
• Biallelic mutations in PLA2G5, encoding group V phospholipase A2, cause benign fleck retina (PMID:22137173)
• Our studies identified a unique function of gV-sPLA2 in activation of macrophages (PMID:23650617)
• Human group V secretory phospholipase A2 is associated with lipid rafts and internalized in a flotillindependent pathway. (PMID:24042857)
• results demonstrate that EPCR is overexpressed and mediates the aggressive behavior of rheumatoid synovial fibroblasts, and is likely driven by group V secretory phospholipase A2 (PMID:24495480)
• There is no association between rs525380 polymorphism of PLA2G5 and coronary heart disease. (PMID:24563418)
• Our results demonstrate the association of the PLA2G5 rs11573191 polymorphism with premature CAD. In our study, it was possible to distinguish one haplotype associated with increased risk of premature CAD and hypertension. (PMID:24959594)
• sPLA2-V plays a thrombogenic role by impairing the ability of EPCR to promote protein C activation. (PMID:25069533)
• expression of PLA2s-IIE and -V correlates with the development of calcification as well as the expression of pro-osteogenic molecules in human aortic valves (PMID:25132377)
• Summarizing, Der p1 and Fel d1 involve phospholipase A2 enzymes in their action. (PMID:25247183)
• The clinical findings in this family suggest a diagnosis of benign familial fleck retina with excellent prognosis, in which the PLA2G5 gene may play a role. (PMID:25549071)
• Data show that phospholipase A2 group IIA, V and X have different target/function related activity. (PMID:26711221)
• Low GV-PLA2 expression is associated with cancer. (PMID:26715269)
• This report provides the first demonstration that Phosphatidylcholine-Isoprostanes are readily hydrolyzed by group IIA, V and X Secretory Phospholipases A2. (PMID:28528433)
• Lysosome-mediated autophagy pathway contributes to gVPLA2 clearance from lung endothelial cells. (PMID:31730773)
• Lipid Profile of Activated Macrophages and Contribution of Group V Phospholipase A2. (PMID:33383652)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pla2g5	ENSMUSG00000041193
rattus_norvegicus	Pla2g5	ENSRNOG00000016838
caenorhabditis_elegans		WBGENE00007419
caenorhabditis_elegans		WBGENE00015406

Paralogs (8): PLA2G10 (ENSG00000069764), PLA2G2D (ENSG00000117215), PLA2G2F (ENSG00000158786), PLA2G1B (ENSG00000170890), PLA2G2C (ENSG00000187980), PLA2G2A (ENSG00000188257), PLA2G2E (ENSG00000188784), OC90 (ENSG00000253117)

Protein

Protein identifiers

Phospholipase A2 group V — P39877 (reviewed: P39877)

Alternative names: PLA2-10, Phosphatidylcholine 2-acylhydrolase 5

All UniProt accessions (1): P39877

UniProt curated annotations — full annotation on UniProt →

Function. Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity), preferentially releasing fatty acyl groups with a low degree of unsaturation such as oleoyl (C18:1) and linoleoyl (C18:2) groups. Hydrolyzes low-density lipoprotein (LDL) phospholipids releasing unsaturated fatty acids that drive macrophage polarization toward an M2 phenotype. May act in an autocrine and paracrine manner. Contributes to lipid remodeling of cellular membranes at different subcellular locations and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of cardiolipin, a major component of the inner membrane of mitochondria and bacterial membranes. Promotes phagocytosis of bacteria in macrophages through production of lysophosphatidylethanolamines. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane. Promotes phagocytosis and killing of ingested fungi likely through controlling phagosome-lysosome fusion and phagosome maturation. Plays a role in biosynthesis of cysteinyl leukotrienes (CysLTs) in myeloid cells. In eosinophils, triggers perinuclear arachidonate release and LTC4 synthesis in a PLA2G4A-independent way. In neutrophils, amplifies CysLTs biosynthesis initiated by PLA2G4A. Promotes immune complex clearance in macrophages via stimulating synthesis of CysLTs, which act through CYSLTR1 to trigger phagocytosis. May regulate antigen processing in antigen-presenting cells. In pulmonary macrophages regulates IL33 production required for activation of group 2 innate lymphoid cells. May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines.

Subcellular location. Secreted. Cell membrane. Cytoplasmic vesicle. Phagosome. Recycling endosome. Golgi apparatus. cis-Golgi network. trans-Golgi network.

Tissue specificity. Heart, placenta and less abundantly, in lung. Detected in the outer and inner plexiform layers of the retina (at protein level). Expressed in monocytes and macrophages.

Post-translational modifications. This enzyme lacks one of the seven disulfide bonds found in similar PLA2 proteins.

Disease relevance. Fleck retina, familial benign (FRFB) [MIM:228980] An autosomal recessive condition associated with a distinctive retinal appearance and no apparent visual or electrophysiologic deficits. Affected individuals are asymptomatic, but fundus examination reveals a striking pattern of diffuse, yellow-white, fleck-like lesions extending to the far periphery of the retina but sparing the foveal region. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by cardiolipin.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Induction. Up-regulated upon M2 macrophage polarization in response to IL4, CSF1 or IL10.

Pathway. Lipid metabolism; phospholipid metabolism. Lipid metabolism; leukotriene B4 biosynthesis. Lipid metabolism; leukotriene C4 biosynthesis.

Similarity. Belongs to the phospholipase A2 family.

RefSeq proteins (1): NP_000920* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001211	PLA2	Family
IPR016090	PLA2-like_dom	Domain
IPR033112	PLA2_Asp_AS	Active_site
IPR033113	PLA2_histidine	Active_site
IPR036444	PLipase_A2_dom_sf	Homologous_superfamily

Pfam: PF00068

Catalyzed reactions (Rhea), 10 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:15801)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H(+) (RHEA:38779)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:40427)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:40431)
• 1’,3’-bis[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = 1’-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3’-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + (9Z)-octadecenoate + H(+) (RHEA:40463)
• 1’-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3’-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = 1’,3’-bis-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + (9Z)-octadecenoate + H(+) (RHEA:40467)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (9Z,12Z)-octadecadienoate + H(+) (RHEA:40815)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = 1-octadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:41215)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoglycerol + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoglycerol + (9Z)-octadecenoate + H(+) (RHEA:44524)
• N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = N-hexadecanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+) (RHEA:45424)

UniProt features (19 total): disulfide bond 6, binding site 4, mutagenesis site 3, sequence variant 2, active site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9QDW	X-RAY DIFFRACTION	2.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P39877-F1	92.19	0.84

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 (2): 67; 111

Ligand- & substrate-binding residues (4): 47; 49; 51; 68

Disulfide bonds (6): 63–117, 70–110, 79–103, 97–108, 46–137, 48–64

Mutagenesis-validated functional residues (3):

Position	Phenotype
50	impairs arachidonate release from cell membranes.
112	decreases arachidonate release from cell membranes; when associated with e-113.
113	decreases arachidonate release from cell membranes; when associated with e-112.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1482788	Acyl chain remodelling of PC
R-HSA-1482801	Acyl chain remodelling of PS
R-HSA-1482839	Acyl chain remodelling of PE
R-HSA-1482922	Acyl chain remodelling of PI
R-HSA-1482925	Acyl chain remodelling of PG
R-HSA-1483166	Synthesis of PA

MSigDB gene sets: 269 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_VACUOLE_ORGANIZATION, RORA1_01, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_VESICLE_ORGANIZATION, KEGG_MAPK_SIGNALING_PATHWAY, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_MEMBRANE_FUSION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (22): fatty acid metabolic process (GO:0006631), phospholipid metabolic process (GO:0006644), positive regulation of phospholipase activity (GO:0010518), positive regulation of macrophage derived foam cell differentiation (GO:0010744), leukotriene biosynthetic process (GO:0019370), low-density lipoprotein particle remodeling (GO:0034374), phosphatidylcholine catabolic process (GO:0034638), negative regulation of T cell proliferation (GO:0042130), phosphatidylcholine metabolic process (GO:0046470), phosphatidylglycerol metabolic process (GO:0046471), arachidonate secretion (GO:0050482), positive regulation of phagocytosis (GO:0050766), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of immune complex clearance by monocytes and macrophages (GO:0090265), phagosome-lysosome fusion (GO:0090385), positive regulation of opsonization (GO:1903028), positive regulation of antifungal innate immune response (GO:1905036), positive regulation of phagosome maturation (GO:1905164), lipid metabolic process (GO:0006629), phagocytosis (GO:0006909), phospholipid catabolic process (GO:0009395), lipid catabolic process (GO:0016042)

GO Molecular Function (7): calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), obsolete calcium-dependent phospholipase A2 activity (GO:0047498), obsolete calcium-independent phospholipase A2 activity (GO:0047499), A2-type glycerophospholipase activity (GO:0004623), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (10): extracellular region (GO:0005576), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), early phagosome (GO:0032009), phagolysosome (GO:0032010), recycling endosome (GO:0055037), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), phagocytic vesicle (GO:0045335)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	6

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
glycerophospholipase activity	2
glycerophospholipid metabolic process	2
positive regulation of immune effector process	2
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
phagocytic vesicle	2
monocarboxylic acid metabolic process	1
organophosphate metabolic process	1
regulation of phospholipase activity	1
positive regulation of lipase activity	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
leukotriene metabolic process	1
icosanoid biosynthetic process	1
plasma lipoprotein particle remodeling	1
phosphatidylcholine metabolic process	1
glycerophospholipid catabolic process	1
T cell proliferation	1
regulation of T cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
icosanoid secretion	1
arachidonate transport	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
immune complex clearance by monocytes and macrophages	1
regulation of immune complex clearance by monocytes and macrophages	1
phagolysosome assembly	1
vesicle fusion	1
opsonization	1
positive regulation of phagocytosis	1
regulation of opsonization	1
positive regulation of innate immune response	1

Protein interactions and networks

STRING

510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G5	PLA2G4D	Q86XP0	957
PLA2G5	PLA2G4B	P0C869	849
PLA2G5	PLA2G3	Q9NZ20	664
PLA2G5	PLA2G6	O60733	613
PLA2G5	PLA2G4A	P47712	601
PLA2G5	PLA2G12A	Q9BZM1	583
PLA2G5	PLA2G12B	Q9BX93	523
PLA2G5	PLAAT3	P53816	483
PLA2G5	PLA2G15	Q8NCC3	477
PLA2G5	PLA2G4C	Q9UP65	434
PLA2G5	ZNF32	P17041	432
PLA2G5	PPP3CA	Q08209	397
PLA2G5	CRNKL1	Q9BZJ0	396
PLA2G5	TRAF3IP3	Q9Y228	393
PLA2G5	APOB	P04114	372

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PLA2G5	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): CACNA2D1 (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), INSR (Affinity Capture-MS), CD109 (Affinity Capture-MS), MESDC1 (Affinity Capture-MS), TTPAL (Affinity Capture-MS), MANBA (Affinity Capture-MS), CACNA2D2 (Affinity Capture-MS), PLA2G5 (Negative Genetic)

ESM2 similar proteins: A0A193CHJ5, D6MKR0, G3DT18, O15496, O42187, P00623, P00624, P00625, P00629, P0DJN6, P0DJN7, P0DP54, P14423, P39877, P45881, P47711, P51433, P62022, P62023, P86974, P97391, Q02509, Q1ZY03, Q2PG83, Q2YHJ2, Q2YHJ7, Q45Z47, Q56JZ2, Q6EAN6, Q6EER4, Q6H3C5, Q6H3C9, Q71QE8, Q7ZTA7, Q7ZTA8, Q800C1, Q800C4, Q805A2, Q8JFB2, Q8JFG2

Diamond homologs: A0A193CHJ5, A8CG84, A8CG86, A8CG90, B3EWP6, C0HJC1, C0HJL8, C0HK05, C0HK16, C0HKC1, C0HKC2, C0HKC3, C0HKC4, C0HLF0, C0HLF7, C0HLL0, C0HM14, C0HMB2, F8QN50, F8QN51, F8QN53, F8QN54, O42187, O42188, O42189, O42190, P00626, P04361, P04417, P06859, P06860, P0C8M1, P0C942, P0C943, P0CAR9, P0CAS2, P0CAS3, P0CAS4, P0CAS5, P0CAS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	91
Likely benign	35
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
812376	NM_000929.3(PLA2G5):c.280dup (p.Val94fs)	Pathogenic

SpliceAI

1190 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20070411:G:GT	donor_gain	1.0000
1:20070462:AGAGG:A	donor_loss	1.0000
1:20070465:GGT:G	donor_loss	1.0000
1:20070411:G:T	donor_gain	0.9900
1:20070444:GATT:G	donor_gain	0.9900
1:20070463:GAG:G	donor_gain	0.9900
1:20086223:GATTG:G	donor_gain	0.9900
1:20086224:ATTGG:A	donor_loss	0.9900
1:20086226:TGGT:T	donor_loss	0.9900
1:20086228:G:A	donor_loss	0.9900
1:20086228:G:GG	donor_gain	0.9900
1:20086229:T:A	donor_loss	0.9900
1:20086230:GA:G	donor_loss	0.9900
1:20090566:A:AG	acceptor_gain	0.9900
1:20090567:G:GG	acceptor_gain	0.9900
1:20090567:GA:G	acceptor_gain	0.9900
1:20070466:G:GG	donor_gain	0.9800
1:20090659:G:GG	donor_gain	0.9800
1:20074557:GAT:G	donor_gain	0.9700
1:20086082:GGT:G	acceptor_gain	0.9700
1:20086214:G:GT	donor_gain	0.9700
1:20090562:TTGCA:T	acceptor_loss	0.9700
1:20090564:GCA:G	acceptor_loss	0.9700
1:20090565:CA:C	acceptor_loss	0.9700
1:20090566:AGAGC:A	acceptor_loss	0.9700
1:20090567:G:A	acceptor_loss	0.9700
1:20090658:A:AG	donor_gain	0.9700
1:20086077:TTCCA:T	acceptor_loss	0.9600
1:20086080:CA:C	acceptor_loss	0.9600
1:20074535:T:G	donor_gain	0.9500

AlphaMissense

891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:20086223:G:C	D61H	0.977
1:20089793:T:A	C64S	0.976
1:20089794:G:C	C64S	0.976
1:20086175:G:T	G45C	0.968
1:20090684:T:A	C137S	0.968
1:20090685:G:C	C137S	0.968
1:20086184:T:A	C48S	0.967
1:20086185:G:C	C48S	0.967
1:20086214:G:C	D58H	0.967
1:20089790:T:A	C63S	0.966
1:20089791:G:C	C63S	0.966
1:20090597:T:A	C108S	0.966
1:20090598:G:C	C108S	0.966
1:20090607:A:T	D111V	0.966
1:20086224:A:T	D61V	0.965
1:20086225:T:A	D61E	0.965
1:20086225:T:G	D61E	0.965
1:20089794:G:A	C64Y	0.965
1:20086178:T:A	C46S	0.963
1:20086179:G:C	C46S	0.963
1:20089795:T:G	C64W	0.962
1:20086185:G:A	C48Y	0.961
1:20090686:C:G	C137W	0.959
1:20089811:T:A	C70S	0.958
1:20089812:G:C	C70S	0.958
1:20090604:G:A	C110Y	0.958
1:20086224:A:C	D61A	0.956
1:20086216:T:A	D58E	0.955
1:20086216:T:G	D58E	0.955
1:20086176:G:A	G45D	0.954

dbSNP variants (sampled 300 via entrez): RS1000045055 (1:20053961 T>A), RS1000049487 (1:20088577 A>G), RS1000075440 (1:20065409 T>C), RS1000093107 (1:20031581 C>T), RS1000125850 (1:20026928 T>G), RS1000174666 (1:20074243 C>A,T), RS1000194778 (1:20028802 G>A), RS1000215021 (1:20064507 G>A), RS1000271680 (1:20071119 T>C), RS1000316640 (1:20071294 A>T), RS1000339504 (1:20077139 G>C), RS1000378022 (1:20035292 G>A), RS1000450608 (1:20076609 G>A), RS1000468890 (1:20034804 C>T), RS1000518352 (1:20047043 C>A)

Disease associations

OMIM: gene MIM:601192 | disease phenotypes: MIM:228980, MIM:605670

GenCC curated gene-disease

Disease	Classification	Inheritance
familial benign flecked retina	Definitive	Autosomal recessive
late-adult onset retinitis pigmentosa	Limited	Autosomal recessive

Mondo (3): familial benign flecked retina (MONDO:0009235), late-onset retinal degeneration (MONDO:0011579), late-adult onset retinitis pigmentosa (MONDO:0009984)

Orphanet (2): Familial benign flecked retina (Orphanet:363989), Late-onset retinal degeneration (Orphanet:67042)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000662	Nyctalopia
HP:0012045	Retinal flecks

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008260_11	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	1.000000e-11
GCST008260_12	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	2.000000e-11
GCST008260_5	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	9.000000e-41
GCST008260_8	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	2.000000e-26
GCST008260_9	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	3.000000e-18

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C565564	Fleck Retina, Familial Benign (supp.)
C565309	Late-Onset Retinal Degeneration (supp.)
C564840	Retinitis Pigmentosa, Late-Adult Onset (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4323 (SINGLE PROTEIN), CHEMBL4524005 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 272 (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
CHEMBL148674	VARESPLADIB	2	272

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phospholipase A₂

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

Ligand	Action	Affinity	Parameter
compound 12e [PMID: 18605714]	Inhibition	7.46	pIC50
BAY-439	Binding	6.67	pKd

Binding affinities (BindingDB)

1 measured of 19 human assays (19 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
dexamethasone (tetramethyl-rhodamine conjugated )	EC50	0.2 nM

ChEMBL bioactivities

55 potent at pChembl≥5 of 61 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	IC50	7	nM	CHEMBL6195034
8.00	IC50	10	nM	CHEMBL5172164
7.46	IC50	35	nM	CHEMBL515637
7.36	IC50	44	nM	CHEMBL148649
7.25	IC50	56	nM	CHEMBL4593409
7.21	IC50	61	nM	CHEMBL6195034
7.00	IC50	100	nM	CHEMBL332993
7.00	IC50	100	nM	CHEMBL514692
6.96	IC50	110	nM	CHEMBL444450
6.94	IC50	114	nM	VARESPLADIB
6.91	IC50	124	nM	VARESPLADIB
6.88	IC50	131	nM	VARESPLADIB
6.85	IC50	140	nM	CHEMBL446349
6.75	IC50	180	nM	CHEMBL4205008
6.67	Kd	214	nM	CHEMBL6195034
6.57	IC50	270	nM	CHEMBL357979
6.36	IC50	440	nM	CHEMBL1644549
6.30	IC50	500	nM	CHEMBL208315
6.30	IC50	500	nM	VARESPLADIB
6.29	IC50	510	nM	CHEMBL4214052
6.29	IC50	510	nM	CHEMBL4205511
6.28	IC50	530	nM	CHEMBL485601
6.26	IC50	550	nM	CHEMBL220842
6.18	IC50	660	nM	CHEMBL373999
6.14	IC50	720	nM	CHEMBL4213094
6.10	IC50	800	nM	CHEMBL346196
6.10	IC50	800	nM	CHEMBL208429
6.00	IC50	1000	nM	CHEMBL223880
5.98	IC50	1050	nM	CHEMBL5200953
5.92	IC50	1200	nM	CHEMBL3769794
5.91	IC50	1220	nM	CHEMBL5194852
5.82	IC50	1530	nM	CHEMBL5207115
5.82	IC50	1500	nM	CHEMBL1644550
5.80	IC50	1600	nM	CHEMBL4205008
5.80	IC50	1600	nM	DIDODECANOYLPHLOROGLUCINOL
5.76	IC50	1730	nM	CHEMBL373870
5.72	IC50	1900	nM	CHEMBL4203027
5.70	IC50	2000	nM	CHEMBL220633
5.68	IC50	2100	nM	CHEMBL4206163
5.68	IC50	2100	nM	CHEMBL4204172
5.66	IC50	2200	nM	CHEMBL4171084
5.65	IC50	2230	nM	CHEMBL4171084
5.64	IC50	2300	nM	CHEMBL4217510
5.57	IC50	2700	nM	CHEMBL4204365
5.52	IC50	3040	nM	CHEMBL5179709
5.43	IC50	3700	nM	CHEMBL4176544
5.29	IC50	5100	nM	CHEMBL4210991
5.26	IC50	5500	nM	CHEMBL4215835
5.23	IC50	5900	nM	CHEMBL4207065
5.20	IC50	6280	nM	CHEMBL5203236

PubChem BioAssay actives

55 with measured affinity, of 284 total; 48 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
2-[2-methyl-1-oxamoyl-3-[(2-phenylphenyl)methyl]indolizin-8-yl]oxyacetic acid	1894720: Inhibition of human group V phospholipase A2 expressed in Escherichia coli BL21(DE3) cells incubated for 10 to 20 mins cells by radiometric assay	ic50	0.0100	uM
(2R)-3-[3-(5-benzyl-2-carbamoylphenyl)phenyl]-2-methylpropanoic acid	1631141: Inhibition of sPLA2 in human HepG2 cells	ic50	0.0140	uM
2-(1-benzyl-2-ethyl-3-oxamoylbenzo[g]indol-4-yl)oxyacetic acid	341249: Inhibition of human group2V phospholipase A2 fluorimetric assay	ic50	0.0350	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxypropanoic acid	341249: Inhibition of human group2V phospholipase A2 fluorimetric assay	ic50	0.0440	uM
2-[2-ethyl-1-oxamoyl-3-[(2-phenylphenyl)methyl]indolizin-8-yl]oxyacetic acid	341249: Inhibition of human group2V phospholipase A2 fluorimetric assay	ic50	0.1000	uM
2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-ethylindol-3-yl]-2-oxoacetamide	341249: Inhibition of human group2V phospholipase A2 fluorimetric assay	ic50	0.1000	uM
1-[3-dodecanoyl-2,4,6-trihydroxy-5-[7-hydroxy-2-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-4-yl]phenyl]dodecan-1-one	389105: Inhibition of human sPLA2 group 5	ic50	0.1100	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxyacetic acid	1614038: Inhibition of human recombinant sPLA2 assessed as reduction in 16:0 LPC formation after 30 mins by HPLC-MS analysis	ic50	0.1140	uM
2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-ethylbenzo[g]indol-3-yl]-2-oxoacetamide	341249: Inhibition of human group2V phospholipase A2 fluorimetric assay	ic50	0.1400	uM
3-[2-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]-4-pyridinyl]-2-methylpropanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	0.1800	uM
2-[2-methyl-3-oxamoyl-1-[(2-phenylphenyl)methyl]indol-4-yl]oxyacetic acid	280829: Inhibition of human group V PLA2 in [3H]oleate-labeled Escherichia coli membrane by radiometric assay	ic50	0.2700	uM
(2S)-4-methyl-2-(2-oxohexadecanoylamino)pentanoic acid	552447: Inhibition of human group 5 sPLA2 by fluorescence assay	ic50	0.4400	uM
2-(1-benzyl-2-ethyl-6-methyl-3-oxamoylindol-4-yl)oxyacetic acid	264370: Inhibition of human recombinant sPLA2 G5	ic50	0.5000	uM
3-[3-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]phenyl]-2-methylpropanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	0.5100	uM
3-[6-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]-2-pyridinyl]-2-methylpropanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	0.5100	uM
1-(3-dodecanoyl-2,4,6-trihydroxy-5-methylphenyl)dodecan-1-one	389105: Inhibition of human sPLA2 group 5	ic50	0.5300	uM
3-[4-(3-decoxy-2-tetradecoxypropoxy)phenyl]-4H-1,2,4-oxadiazol-5-one	280829: Inhibition of human group V PLA2 in [3H]oleate-labeled Escherichia coli membrane by radiometric assay	ic50	0.5500	uM
Dexamethasone	1801101: sPLA2V Activity Assay from Article 10.1111/cbdd.12457: “Synthesis, Molecular Modeling, and Biological Evaluation of Novel 1, 3-Diphenyl-2-propen-1-one Based Pyrazolines as Anti-inflammatory Agents.”	ic50	0.6200	uM
3-[4-(2-tetradecoxy-3-trityloxypropoxy)phenyl]-4H-1,2,4-oxadiazol-5-one	280829: Inhibition of human group V PLA2 in [3H]oleate-labeled Escherichia coli membrane by radiometric assay	ic50	0.6600	uM
3-[2-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]-4-pyridinyl]propanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	0.7200	uM
2-(1-benzyl-2,6-dimethyl-3-oxamoylindol-4-yl)oxyacetic acid	264370: Inhibition of human recombinant sPLA2 G5	ic50	0.8000	uM
2-(1-benzyl-2-methyl-3-oxamoylindol-4-yl)oxyacetic acid	264370: Inhibition of human recombinant sPLA2 G5	ic50	0.8000	uM
4-[[2-octadecoxy-3-[4-[(5-oxo-4H-1,2,4-oxadiazol-3-yl)methyl]phenoxy]propoxy]methyl]benzonitrile	280829: Inhibition of human group V PLA2 in [3H]oleate-labeled Escherichia coli membrane by radiometric assay	ic50	1.0000	uM
1-(2,4-dihydroxyphenyl)-5H-pyrrolo[1,2-a]quinoxalin-4-one	1859294: Inhibition of human PLA2G5	ic50	1.0500	uM
(2S)-3-methyl-2-(2-oxohexadecanoylamino)butanoic acid	1282066: Inhibition of human group 5 secreted phospholipase A2 by fluorescence assay	ic50	1.2000	uM
3-[(2E)-2-[(3-methoxyphenyl)methylidene]hydrazinyl]-1H-quinoxalin-2-one	1859294: Inhibition of human PLA2G5	ic50	1.2200	uM
(2R)-4-methyl-2-(2-oxohexadecanoylamino)pentanoic acid	552447: Inhibition of human group 5 sPLA2 by fluorescence assay	ic50	1.5000	uM
1-(2,4-dinitrophenyl)-5H-pyrrolo[1,2-a]quinoxalin-4-one	1859294: Inhibition of human PLA2G5	ic50	1.5300	uM
1-(3-dodecanoyl-2,4,6-trihydroxyphenyl)dodecan-1-one	389105: Inhibition of human sPLA2 group 5	ic50	1.6000	uM
4-[[3-[4-[(5-oxo-4H-1,2,4-oxadiazol-3-yl)methyl]phenoxy]-2-tetradecoxypropoxy]methyl]benzonitrile	280829: Inhibition of human group V PLA2 in [3H]oleate-labeled Escherichia coli membrane by radiometric assay	ic50	1.7300	uM
2-[[6-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]-2-pyridinyl]methyl]butanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	1.9000	uM
3-[4-(3-benzhydryloxy-2-tetradecoxypropoxy)phenyl]-4H-1,2,4-oxadiazol-5-one	280829: Inhibition of human group V PLA2 in [3H]oleate-labeled Escherichia coli membrane by radiometric assay	ic50	2.0000	uM
3-[4-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]-2-pyridinyl]propanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	2.1000	uM
3-[3-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]phenyl]-2-methoxypropanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	2.1000	uM
3-[3-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]phenyl]propanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	2.2000	uM
3-[6-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]-2-pyridinyl]propanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	2.3000	uM
3-[4-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]pyrazol-1-yl]propanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	2.7000	uM
1-(3,4-dichlorophenyl)-5H-pyrrolo[1,2-a]quinoxalin-4-one	1859294: Inhibition of human PLA2G5	ic50	3.0400	uM
3-[3-[2-carbamoyl-6-(trifluoromethyl)indol-1-yl]phenyl]propanoic acid	1356220: Inhibition of recombinant human sPLA2-5 expressed in Escherichia coli BL21(DE3) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins	ic50	3.7000	uM
(3S)-3-[3-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]phenyl]butanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	5.1000	uM
N-(4-chlorophenyl)-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(4,7-dimethoxynaphthalen-1-yl)-3,4-dihydropyrazole-2-carboxamide	1801101: sPLA2V Activity Assay from Article 10.1111/cbdd.12457: “Synthesis, Molecular Modeling, and Biological Evaluation of Novel 1, 3-Diphenyl-2-propen-1-one Based Pyrazolines as Anti-inflammatory Agents.”	ic50	5.1200	uM
3-[6-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]-2-pyridinyl]butanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	5.5000	uM
3-[5-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]furan-2-yl]propanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	5.9000	uM
3-[(2E)-2-(thiophen-2-ylmethylidene)hydrazinyl]-1H-quinoxalin-2-one	1859294: Inhibition of human PLA2G5	ic50	6.2800	uM
5-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(4,7-dimethoxynaphthalen-1-yl)-3,4-dihydropyrazole-2-carbothioamide	1801101: sPLA2V Activity Assay from Article 10.1111/cbdd.12457: “Synthesis, Molecular Modeling, and Biological Evaluation of Novel 1, 3-Diphenyl-2-propen-1-one Based Pyrazolines as Anti-inflammatory Agents.”	ic50	7.1200	uM
5-(1-benzofuran-2-yl)-N-(4-chlorophenyl)-3-(2,3-dimethoxynaphthalen-1-yl)-3,4-dihydropyrazole-2-carboxamide	1801101: sPLA2V Activity Assay from Article 10.1111/cbdd.12457: “Synthesis, Molecular Modeling, and Biological Evaluation of Novel 1, 3-Diphenyl-2-propen-1-one Based Pyrazolines as Anti-inflammatory Agents.”	ic50	8.4600	uM
(3R)-3-[3-[2-carbamoyl-6-(trifluoromethoxy)indol-1-yl]phenyl]butanoic acid	1384821: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay	ic50	8.6000	uM
5-(1-benzofuran-2-yl)-3-(2,3-dimethoxynaphthalen-1-yl)-3,4-dihydropyrazole-2-carbothioamide	1801101: sPLA2V Activity Assay from Article 10.1111/cbdd.12457: “Synthesis, Molecular Modeling, and Biological Evaluation of Novel 1, 3-Diphenyl-2-propen-1-one Based Pyrazolines as Anti-inflammatory Agents.”	ic50	9.1700	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
N-Formylmethionine Leucyl-Phenylalanine	increases secretion, increases abundance, increases reaction, increases activity	2
propionaldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
isoliquiritigenin	decreases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
SB 203347	decreases activity	1
indoxam	decreases activity	1
enzalutamide	decreases expression	1
Decitabine	affects cotreatment, increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation	1
Biological Factors	increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Methamphetamine	increases expression	1
Methapyrilene	increases methylation	1
Sarin	increases expression, decreases expression	1
Silicon Dioxide	increases expression	1
Dihydrotestosterone	increases expression	1
Zymosan	decreases activity, increases secretion	1
Aflatoxin B1	increases methylation	1
Arachidonic Acid	increases abundance, increases reaction	1
Leukotriene C4	increases abundance, increases reaction	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

43 unique, capped per target: 41 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011802	Binding	Inhibition of human group 5 sPLA2 at 0.091 mol fraction by mixed micelle-based assay	Synthesis of polyfluoro ketones for selective inhibition of human phospholipase A2 enzymes. — J Med Chem
CHEMBL6193890	Functional	Inhibition of human PLA2G5 in recombinant human protein using Biochemical human PLA2G5 assay ( Substrate: Red/Green BODIPY® PC-A2; PLA2-G5-dependent increase in BODIPY® FL fluorescence emission was measured in a Pherastar plate reader (BMG)	Data for DCP probe BAY-439

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03510234	Not specified	UNKNOWN	Self-confidence Study in Patients With Argus II Artificial Retina
NCT04360291	Not specified	UNKNOWN	Impact of Visual Field Restriction on Visual Exploration
NCT04419285	Not specified	UNKNOWN	Mobility Protocol Adapted for Advanced Visually Impaired Subjects
NCT05179460	Not specified	COMPLETED	A Study of Pentosan Polysulfate Sodium and the Development of Pigmentary Maculopathy and Pigmentary Retinopathy
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases