PLA2G2E

Summary

PLA2G2E (phospholipase A2 group IIE, HGNC:13414) is a protein-coding gene on chromosome 1p36.13, encoding Group IIE secretory phospholipase A2 (Q9NZK7). Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids.

Enables calcium ion binding activity and calcium-dependent phospholipase A2 activity. Predicted to be involved in phosphatidylcholine metabolic process and phosphatidylglycerol metabolic process. Predicted to act upstream of or within low-density lipoprotein particle remodeling. Predicted to be located in extracellular region.

Source: NCBI Gene 30814 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 33 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014589

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13414
Approved symbol	PLA2G2E
Name	phospholipase A2 group IIE
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188784
Ensembl biotype	protein_coding
OMIM	618320
Entrez	30814

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000375116

RefSeq mRNA: 1 — MANE Select: NM_014589 NM_014589

CCDS: CCDS200

Canonical transcript exons

ENST00000375116 — 4 exons

Exon	Start	End
ENSE00000576423	19922298	19922404
ENSE00000872994	19922617	19922755
ENSE00001465801	19920009	19920449
ENSE00001465806	19923520	19923617

Expression profiles

Bgee: expression breadth broad, 21 present calls, max score 61.37.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	61.37	gold quality
biceps brachii	UBERON:0001507	59.70	gold quality
skin of hip	UBERON:0001554	51.33	silver quality
Brodmann (1909) area 46	UBERON:0006483	48.95	gold quality
deltoid	UBERON:0001476	46.50	gold quality
skeletal muscle tissue	UBERON:0001134	45.80	gold quality
adult organism	UBERON:0007023	44.91	gold quality
vastus lateralis	UBERON:0001379	44.90	gold quality
quadriceps femoris	UBERON:0001377	44.78	gold quality
pharyngeal mucosa	UBERON:0000355	43.82	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
muscle tissue	UBERON:0002385	43.28	gold quality
jejunum	UBERON:0002115	42.58	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
gingiva	UBERON:0001828	42.06	gold quality
tonsil	UBERON:0002372	41.98	gold quality
substantia nigra pars compacta	UBERON:0001965	41.90	gold quality
ventral tegmental area	UBERON:0002691	41.88	gold quality
nasal cavity epithelium	UBERON:0005384	41.61	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
parotid gland	UBERON:0001831	40.77	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
medulla oblongata	UBERON:0001896	40.53	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.31

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 10)

• promotes stimulus-induced arachidonic acid release and prostaglandin (PG) production similar to those elicited by HSPG-dependent sPLA(2)s, suggesting that this enzyme plays a role in the inflammatory process. (PMID:11922621)
• Single-nucleotide polymorphism in PLA2G2E gene is associated with ulcerative colitis. (PMID:23511034)
• 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)
• sPLA(2) -IIE regulates lipolysis in adipocytes, likely through the ERK/HSL signaling pathway (PMID:25755141)
• that are responsible for interacting with inhibitors, and illustrated the difference in the inhibitor binding pocket with other secretory phospholipase A2s. (PMID:28883454)
• Residue Asn21 acts as a switch for calcium binding to modulate the enzymatic activity of human phospholipase A2 group IIE. (PMID:32659444)
• The atypical binding mechanism of second calcium on phospholipase A2 group IIE. (PMID:33894413)
• [Effect of E54 mutation of human secreted phospholipase A2 GIIE on substrate selectivity]. (PMID:34327916)
• PLA2G2E-mediated lipid metabolism triggers brain-autonomous neural repair after ischemic stroke. (PMID:37490917)
• Secreted phospholipase PLA2G2E contributes to regulation of T cell immune response against influenza virus infection. (PMID:38591879)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pla2g2e	ENSMUSG00000028751
rattus_norvegicus	Pla2g2e	ENSRNOG00000017024
caenorhabditis_elegans		WBGENE00007419
caenorhabditis_elegans		WBGENE00015406

Paralogs (8): PLA2G10 (ENSG00000069764), PLA2G2D (ENSG00000117215), PLA2G5 (ENSG00000127472), PLA2G2F (ENSG00000158786), PLA2G1B (ENSG00000170890), PLA2G2C (ENSG00000187980), PLA2G2A (ENSG00000188257), OC90 (ENSG00000253117)

Protein

Protein identifiers

Group IIE secretory phospholipase A2 — Q9NZK7 (reviewed: Q9NZK7)

Alternative names: Phosphatidylcholine 2-acylhydrolase 2E

All UniProt accessions (1): Q9NZK7

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), releasing various unsaturated fatty acids including oleoate, linoleoate, arachidonate, docosahexaenoate and lysophosphatidylethanolamines in preference to lysophosphatidylcholines. In response to high-fat diet, hydrolyzes minor lipoprotein phospholipids including phosphatidylserines, phosphatidylinositols and phosphatidylglycerols, altering lipoprotein composition and fat storage in adipose tissue and liver. May act in an autocrine and paracrine manner. Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria. Acts as a hair follicle phospholipase A2. Selectively releases lysophosphatidylethanolamines (LPE) and various unsaturated fatty acids in skin to regulate hair follicle homeostasis. May regulate the inflammatory response by releasing arachidonate, a precursor of prostaglandins and leukotrienes. Upon allergen exposure, may participate in allergic inflammatory response by enhancing leukotriene C4 synthesis and degranulation in mast cells.

Subcellular location. Secreted. Cytoplasm.

Tissue specificity. Restricted to the brain, heart, lung, and placenta.

Cofactor. Binds 2 Ca(2+) ions per subunit. One ion binds at a conserved binding site (GCXCG), whereas the second ion binds at a flexible site and may act as a supplemental electrophile as well as a backup.

Induction. Up-regulated by inflammatory cytokine IL1B.

Similarity. Belongs to the phospholipase A2 family.

RefSeq proteins (1): NP_055404* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00068

Catalyzed reactions (Rhea), 11 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-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:40431)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:40811)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (9Z,12Z)-octadecadienoate + H(+) (RHEA:40815)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+) (RHEA:40911)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:41223)
• 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine + H2O = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41231)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoglycerol + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoglycerol + (9Z)-octadecenoate + H(+) (RHEA:44524)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + H2O = a 1-acyl-sn-glycero-3-phosphoethanolamine + a fatty acid + H(+) (RHEA:44604)
• 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1’-sn-glycerol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1’-sn-glycerol) + hexadecanoate + H(+) (RHEA:45472)

UniProt features (37 total): binding site 8, disulfide bond 7, helix 7, mutagenesis site 5, turn 3, strand 3, active site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5Y5E	X-RAY DIFFRACTION	1.8
5WZO	X-RAY DIFFRACTION	1.9
5WZW	X-RAY DIFFRACTION	1.95
5WZM	X-RAY DIFFRACTION	2
6KQU	X-RAY DIFFRACTION	2
5WZU	X-RAY DIFFRACTION	2.2
5WZV	X-RAY DIFFRACTION	2.2
5WZS	X-RAY DIFFRACTION	2.3
5WZT	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZK7-F1	91.10	0.82

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): 65; 109

Ligand- & substrate-binding residues (8): 130; 132; 41; 43; 45; 47; 49; 66

Disulfide bonds (7): 44–135, 46–62, 61–115, 67–142, 68–108, 77–101, 95–106

Mutagenesis-validated functional residues (5):

Position	Phenotype
40	significantly decreases the catalytic efficiency.
41	significantly decreases the catalytic efficiency.
65	loss of catalytic activity.
66	loss of catalytic activity.
132	significantly decreases the catalytic efficiency.

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: 101 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, MAZ_Q6, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_PROTEIN_LIPID_COMPLEX_ORGANIZATION, GOBP_ORGANIC_ANION_TRANSPORT

GO Biological Process (8): phospholipid metabolic process (GO:0006644), inflammatory response (GO:0006954), lipid catabolic process (GO:0016042), low-density lipoprotein particle remodeling (GO:0034374), phosphatidylcholine metabolic process (GO:0046470), phosphatidylglycerol metabolic process (GO:0046471), arachidonate secretion (GO:0050482), lipid metabolic process (GO:0006629)

GO Molecular Function (7): A2-type glycerophospholipase activity (GO:0004623), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), obsolete calcium-dependent phospholipase A2 activity (GO:0047498), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), cytoplasm (GO:0005737)

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
glycerophospholipid metabolic process	2
cellular anatomical structure	2
organophosphate metabolic process	1
defense response	1
catabolic process	1
plasma lipoprotein particle remodeling	1
icosanoid secretion	1
arachidonate transport	1
primary metabolic process	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
metal ion binding	1
lipid binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G2E	PLA2G3	Q9NZ20	696
PLA2G2E	PLA2G12A	Q9BZM1	623
PLA2G2E	RNF186	Q9NXI6	609
PLA2G2E	PLA2G12B	Q9BX93	605
PLA2G2E	PLA2R1	Q13018	603
PLA2G2E	OTUD3	Q5T2D3	523
PLA2G2E	PLA2G6	O60733	493
PLA2G2E	PLA2G4A	P47712	472
PLA2G2E	ENPP2	Q13822	453
PLA2G2E	CYP2E1	P05181	445
PLA2G2E	PLA2G4F	Q68DD2	433
PLA2G2E	PLA2G4D	Q86XP0	432
PLA2G2E	PLA2G4C	Q9UP65	412
PLA2G2E	PLAAT3	P53816	405
PLA2G2E	PNPLA8	Q9NP80	387

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MALL	PLA2G2E	psi-mi:“MI:0915”(physical association)	0.560
PLA2G2E	ITGA5	psi-mi:“MI:0914”(association)	0.350
MALL	PLA2G2E	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): TST (Negative Genetic), PLA2G2E (Negative Genetic), PLA2G2E (Positive Genetic), PLA2G2E (Two-hybrid), PPP4R2 (Affinity Capture-MS), ITGA5 (Affinity Capture-MS), SMEK2 (Affinity Capture-MS), SMEK1 (Affinity Capture-MS), PLA2G2E (Cross-Linking-MS (XL-MS))

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: A0A411EZW9, A8CG78, A8CG84, A8CG86, A8CG87, A8E2V8, B5U6Z2, B6CQR5, C0HJC1, C0HKC3, C0HKC4, C0HLF0, C0HLL2, C0HMB2, C3W4R6, C9DPL5, F8QN51, F8QN52, F8QN53, F8QN54, G3DT18, O42187, O42188, O42189, O42190, P00626, P04417, P06860, P08878, P0CAR9, P0DJP4, P0DKR3, P0DKR5, P0DKU1, P0DPS4, P11407, P14420, P14423, P14424, P14555

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

925 predictions. Top by Δscore:

Variant	Effect	Δscore
1:19922610:T:TA	donor_gain	1.0000
1:19922612:CTCA:C	donor_loss	1.0000
1:19922613:TCA:T	donor_loss	1.0000
1:19922614:CACCA:C	donor_loss	1.0000
1:19922615:A:AC	donor_gain	1.0000
1:19922615:ACCAG:A	donor_loss	1.0000
1:19922616:C:A	donor_loss	1.0000
1:19922616:C:CC	donor_gain	1.0000
1:19922616:CCAGT:C	donor_gain	1.0000
1:19922751:AGCCA:A	acceptor_gain	1.0000
1:19922752:GCCA:G	acceptor_gain	1.0000
1:19922753:CCA:C	acceptor_gain	1.0000
1:19922753:CCAC:C	acceptor_gain	1.0000
1:19922754:CA:C	acceptor_gain	1.0000
1:19922754:CAC:C	acceptor_gain	1.0000
1:19922755:ACT:A	acceptor_loss	1.0000
1:19922756:C:CC	acceptor_gain	1.0000
1:19922756:CTGC:C	acceptor_loss	1.0000
1:19922759:C:CT	acceptor_gain	1.0000
1:19922293:CCTA:C	donor_loss	0.9900
1:19922294:CT:C	donor_loss	0.9900
1:19922296:A:AC	donor_gain	0.9900
1:19922296:ACC:A	donor_loss	0.9900
1:19922297:C:CC	donor_gain	0.9900
1:19922297:C:G	donor_loss	0.9900
1:19922297:CCG:C	donor_gain	0.9900
1:19922403:ACC:A	acceptor_loss	0.9900
1:19922405:CT:C	acceptor_loss	0.9900
1:19922406:T:A	acceptor_loss	0.9900
1:19922615:AC:A	donor_gain	0.9900

AlphaMissense

923 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:19920332:C:G	C135S	0.991
1:19920333:A:T	C135S	0.991
1:19922621:C:G	D59H	0.990
1:19922669:C:A	G43C	0.990
1:19920410:T:A	D109V	0.988
1:19922399:C:G	C62S	0.988
1:19922400:A:T	C62S	0.988
1:19922659:C:G	C46S	0.987
1:19922660:A:T	C46S	0.987
1:19922665:C:G	C44S	0.987
1:19922666:A:T	C44S	0.987
1:19920389:A:C	F116C	0.985
1:19922399:C:T	C62Y	0.985
1:19922668:C:A	G43V	0.985
1:19922668:C:T	G43D	0.985
1:19920392:C:G	C115S	0.984
1:19920393:A:T	C115S	0.984
1:19922333:T:C	Y84C	0.984
1:19920389:A:G	F116S	0.983
1:19920410:T:G	D109A	0.983
1:19920413:C:G	C108S	0.983
1:19920414:A:T	C108S	0.983
1:19922619:G:C	D59E	0.983
1:19922619:G:T	D59E	0.983
1:19922659:C:T	C46Y	0.983
1:19922398:G:C	C62W	0.982
1:19922620:T:A	D59V	0.982
1:19920419:C:G	C106S	0.981
1:19920420:A:T	C106S	0.981
1:19922354:C:G	C77S	0.981

dbSNP variants (sampled 300 via entrez): RS1000932949 (1:19923178 G>A,C), RS1001054964 (1:19920775 C>T), RS1001180617 (1:19923280 G>A,C), RS1001436590 (1:19922712 GATC>G), RS1002943569 (1:19920770 C>A,T), RS1002956802 (1:19920578 T>C,G), RS1003927786 (1:19924301 A>C), RS1004832547 (1:19919845 G>T), RS1004899082 (1:19921202 G>A,C), RS1005007042 (1:19924894 C>G,T), RS1005269754 (1:19919555 C>G,T), RS1006006207 (1:19920328 G>A), RS1006087724 (1:19925254 AAAAT>A,AAAATAAAT), RS1006122446 (1:19920218 AG>A), RS1006894000 (1:19920737 CCTAA>C)

Disease associations

OMIM: gene MIM:618320 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000311_4	Ulcerative colitis	5.000000e-13
GCST000527_9	Ulcerative colitis	2.000000e-11
GCST000624_1	Ulcerative colitis	3.000000e-08
GCST000624_11	Ulcerative colitis	2.000000e-10
GCST000624_21	Ulcerative colitis	2.000000e-21
GCST001938_4	Ulcerative colitis	7.000000e-09
GCST008260_10	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	9.000000e-17
GCST008260_12	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	2.000000e-11
GCST008260_3	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	4.000000e-138
GCST008260_4	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	6.000000e-79
GCST008260_6	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	7.000000e-33
GCST008260_7	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	2.000000e-31

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2154 (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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 12e [PMID: 18605714]	Inhibition	8.15	pIC50

ChEMBL bioactivities

19 potent at pChembl≥5 of 20 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	IC50	7	nM	CHEMBL514692
8.15	IC50	7	nM	CHEMBL515637
8.05	IC50	9	nM	CHEMBL148649
8.00	IC50	10	nM	CHEMBL5172164
8.00	IC50	10	nM	CHEMBL332993
7.80	IC50	16	nM	CHEMBL446349
7.70	IC50	20	nM	CHEMBL514841
7.30	IC50	50	nM	CHEMBL208315
7.30	IC50	50	nM	VARESPLADIB
7.25	IC50	56	nM	CHEMBL4593409
7.12	IC50	75	nM	CHEMBL346196
7.05	IC50	90	nM	CHEMBL517821
6.94	IC50	114	nM	VARESPLADIB
6.90	IC50	125	nM	CHEMBL208429
6.88	IC50	131	nM	VARESPLADIB
6.58	IC50	260	nM	CHEMBL514705
6.08	IC50	840	nM	CHEMBL506485
5.89	IC50	1300	nM	CHEMBL504813

PubChem BioAssay actives

20 with measured affinity, of 48 total; 16 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-(1-benzyl-2-ethyl-3-oxamoylbenzo[g]indol-4-yl)oxyacetic acid	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	0.0070	uM
2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-ethylindol-3-yl]-2-oxoacetamide	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	0.0070	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxypropanoic acid	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	0.0090	uM
2-[2-methyl-1-oxamoyl-3-[(2-phenylphenyl)methyl]indolizin-8-yl]oxyacetic acid	1894719: Inhibition of human group IIE phospholipase A2 expressed in Escherichia coli BL21 cells incubated for 10 to 20 mins cells by radiometric assay	ic50	0.0100	uM
2-[2-ethyl-1-oxamoyl-3-[(2-phenylphenyl)methyl]indolizin-8-yl]oxyacetic acid	341245: Inhibition of human group2E phospholipase A2 fluorimetric 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-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-ethylbenzo[g]indol-3-yl]-2-oxoacetamide	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	0.0160	uM
2-(1-benzyl-2-ethyl-4-methoxybenzo[g]indol-3-yl)-2-oxoacetamide	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	0.0200	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxyacetic acid	264368: Inhibition of human recombinant sPLA2 G2E	ic50	0.0500	uM
2-(1-benzyl-2-ethyl-6-methyl-3-oxamoylindol-4-yl)oxyacetic acid	264368: Inhibition of human recombinant sPLA2 G2E	ic50	0.0500	uM
2-(1-benzyl-2-methyl-3-oxamoylindol-4-yl)oxyacetic acid	264368: Inhibition of human recombinant sPLA2 G2E	ic50	0.0750	uM
2-[2-ethyl-8-(2-oxopropoxy)-3-[(2-phenylphenyl)methyl]indolizin-1-yl]-2-oxoacetamide	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	0.0900	uM
2-(1-benzyl-2,6-dimethyl-3-oxamoylindol-4-yl)oxyacetic acid	264368: Inhibition of human recombinant sPLA2 G2E	ic50	0.1250	uM
2-[1-benzyl-2-(2-methylpropyl)-3-oxamoylbenzo[g]indol-4-yl]oxyacetic acid	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	0.2600	uM
2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-(2-methylpropyl)benzo[g]indol-3-yl]-2-oxoacetamide	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	0.8400	uM
2-[1-benzyl-2-(2-methylpropyl)-3-oxamoylindol-4-yl]oxyacetic acid	341245: Inhibition of human group2E phospholipase A2 fluorimetric assay	ic50	1.3000	uM

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3773529	Binding	Inhibition of human group 2E secreted phospholipase A2 assessed as remaining activity at 1000 nM by fluorescence assay	Development of a potent 2-oxoamide inhibitor of secreted phospholipase A2 guided by molecular docking calculations and molecular dynamics simulations. — Bioorg Med Chem

Clinical trials (associated diseases)

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