PLA2G2D

Summary

PLA2G2D (phospholipase A2 group IID, HGNC:9033) is a protein-coding gene on chromosome 1p36.12, encoding Group IID secretory phospholipase A2 (Q9UNK4). Secretory calcium-dependent phospholipase A2 that primarily targets extracellular lipids, exerting anti-inflammatory and immunosuppressive functions.

This gene encodes a secreted member of the phospholipase A2 family, and is found in a cluster of related family members on chromosome 1. Phospholipase A2 family members hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce lysophospholipids and free fatty acid. This gene may be involved in inflammation and immune response, and in weight loss associated with chronic obstructive pulmonary disease. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 26279 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 24 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_012400

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9033
Approved symbol	PLA2G2D
Name	phospholipase A2 group IID
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	sPLA2S
Ensembl gene	ENSG00000117215
Ensembl biotype	protein_coding
OMIM	605630
Entrez	26279

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000375105, ENST00000617227

RefSeq mRNA: 2 — MANE Select: NM_012400 NM_001271814, NM_012400

CCDS: CCDS203, CCDS72721

Canonical transcript exons

ENST00000375105 — 4 exons

Exon	Start	End
ENSE00000755639	20115507	20115613
ENSE00000873027	20116333	20116477
ENSE00001465773	20119459	20119536
ENSE00001887081	20111939	20114259

Expression profiles

Bgee: expression breadth broad, 88 present calls, max score 87.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2399 / max 73.3543, expressed in 68 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10715	0.2399	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	87.76	gold quality
vermiform appendix	UBERON:0001154	84.12	gold quality
caecum	UBERON:0001153	79.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.39	gold quality
bone marrow cell	CL:0002092	74.02	gold quality
olfactory bulb	UBERON:0002264	70.18	gold quality
type B pancreatic cell	CL:0000169	70.11	gold quality
epithelium of nasopharynx	UBERON:0001951	69.80	gold quality
rectum	UBERON:0001052	69.44	gold quality
decidua	UBERON:0002450	69.38	gold quality
spleen	UBERON:0002106	69.20	gold quality
cerebellar vermis	UBERON:0004720	66.32	gold quality
mucosa of urinary bladder	UBERON:0001259	65.76	gold quality
diaphragm	UBERON:0001103	65.20	gold quality
mucosa of transverse colon	UBERON:0004991	64.44	gold quality
superficial temporal artery	UBERON:0001614	64.17	gold quality
cervix squamous epithelium	UBERON:0006922	64.00	gold quality
gall bladder	UBERON:0002110	63.84	gold quality
thymus	UBERON:0002370	62.40	silver quality
cervix epithelium	UBERON:0004801	61.67	gold quality
quadriceps femoris	UBERON:0001377	61.59	gold quality
vastus lateralis	UBERON:0001379	61.25	gold quality
male germ cell	CL:0000015	60.61	gold quality
tonsil	UBERON:0002372	60.55	gold quality
superior surface of tongue	UBERON:0007371	60.46	silver quality
layer of synovial tissue	UBERON:0007616	60.44	gold quality
tongue squamous epithelium	UBERON:0006919	59.76	gold quality
sperm	CL:0000019	59.38	gold quality
saphenous vein	UBERON:0007318	58.93	gold quality
inferior vagus X ganglion	UBERON:0005363	58.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

69 targeting PLA2G2D, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1275	99.47	67.90	2749

Literature-anchored findings (GeneRIF, showing 10)

• TNF-alpha & IFN-gamma induce gene expression of a novel secretory PLA(2)IIDin human airway epithelial cells. The possibility that it is involved in cytokine-mediated inflammation in the respiratory tract is inferred. (PMID:12396716)
• The GIID sPLA2 is clustered on human chromosome 1 and is differentially expressed in tissues, suggesting it has unique function. (PMID:15052324)
• overexpression of human secretory phospholipase A2 group IIA leads to an enhanced delivery of cholesterol from phospholipolysed lipoproteins to the liver (PMID:15379211)
• These results suggest that sPLA2-IID may be one of the susceptibility genes that contribute to body weight loss in patients with COPD. (PMID:16002569)
• lipopolysaccharides inhibit interferon gamma-induced gene expression of secretory phospholipase A2 type IID in human monocyte-derived macrophages (PMID:16897354)
• The distribution pattern of sPLA2S in intact spermatozoa might be an additional parameter for evaluating sperm quality (PMID:18958346)
• The Gly80Ser polymorphism may be associated with the body weight loss seen in chronic obstructive pulmonary disease patients. PLA2G2D-Ser enhances the expression of IL-6 and IL-8 compared with PLA2G2D-Gly. (PMID:19365107)
• sPLA(2)-IID is present at the head and midpiece in the human sperm, and its activation seems to be involved in acrosomal exocytosis. (PMID:22240557)
• phospholipid bilayer permeabilization by the hsPLA2GIID is independent of catalytic activity. (PMID:22490726)
• found to induce PLA2G2D expression in mice and in human monocyte-derived macrophages (PMID:26392224)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pla2g2d	ENSMUSG00000041202
rattus_norvegicus	Pla2g2d	ENSRNOG00000016826
caenorhabditis_elegans		WBGENE00007419
caenorhabditis_elegans		WBGENE00015406

Paralogs (8): PLA2G10 (ENSG00000069764), PLA2G5 (ENSG00000127472), PLA2G2F (ENSG00000158786), PLA2G1B (ENSG00000170890), PLA2G2C (ENSG00000187980), PLA2G2A (ENSG00000188257), PLA2G2E (ENSG00000188784), OC90 (ENSG00000253117)

Protein

Protein identifiers

Group IID secretory phospholipase A2 — Q9UNK4 (reviewed: Q9UNK4)

Alternative names: PLA2IID, Phosphatidylcholine 2-acylhydrolase 2D, Secretory-type PLA, stroma-associated homolog

All UniProt accessions (1): Q9UNK4

UniProt curated annotations — full annotation on UniProt →

Function. Secretory calcium-dependent phospholipase A2 that primarily targets extracellular lipids, exerting anti-inflammatory and immunosuppressive functions. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines. In draining lymph nodes, selectively hydrolyzes diacyl and alkenyl forms of phosphatidylethanolamines, releasing omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoate and docosahexaenoate that are precursors of the anti-inflammatory lipid mediators, resolvins. During the resolution phase of acute inflammation drives docosahexaenoate-derived resolvin D1 synthesis, which suppresses dendritic cell activation and T-helper 1 immune response. May act in an autocrine and paracrine manner. Via a mechanism independent of its catalytic activity, promotes differentiation of regulatory T cells (Tregs) and participates in the maintenance of immune tolerance. May contribute to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in pancreas and spleen and less abundantly in colon, thymus, placenta, small intestine, and prostate.

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

Similarity. Belongs to the phospholipase A2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UNK4-1	1	yes
Q9UNK4-2	2

RefSeq proteins (2): NP_001258743, NP_036532* (*=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

Enzyme classification (BRENDA):

• EC 3.1.1.4 — phospholipase A2 (BRENDA: 129 organisms, 452 substrates, 710 inhibitors, 90 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PHOSPHATIDYLCHOLINE	0.05–17	12
1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.94–13.85	7
PHOSPHATIDYLETHANOLAMINE	0.02–10.5	5
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
(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
(3R,3AS,5AS,9BR)-3,5A,9-TRIMETHYL-3A,4,5,5A-TETR	0.734	1
(3R,3AS,6R,8S,9BS)-6,8-DIHYDROXY-3,6,9-TRIMETHYL	0.744	1
(3R,3AS,6R,8S,9BS)-8-HYDROXY-3,6,9-TRIMETHYL-2-O	0.738	1
(3R,3AS,6R,9BS)-3,6,9-TRIMETHYL-2,8-DIOXO-2,3,3A	0.742	1

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-(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-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1’-sn-glycerol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1’-sn-glycerol) + (9Z)-octadecenoate + H(+) (RHEA:40919)
• 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)
• 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 (24 total): disulfide bond 7, sequence variant 6, binding site 4, splice variant 2, active site 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNK4-F1	92.28	0.87

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; 112

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

Disulfide bonds (7): 48–64, 63–118, 69–145, 70–111, 79–104, 97–109, 46–138

Glycosylation sites (1): 89

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: 162 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE

GO Biological Process (12): CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation (GO:0002361), regulation of acute inflammatory response to antigenic stimulus (GO:0002864), phospholipid metabolic process (GO:0006644), inflammatory response (GO:0006954), lipid catabolic process (GO:0016042), negative regulation of T cell proliferation (GO:0042130), phosphatidylethanolamine metabolic process (GO:0046337), phosphatidylcholine metabolic process (GO:0046470), phosphatidylglycerol metabolic process (GO:0046471), arachidonate secretion (GO:0050482), lipid metabolic process (GO:0006629), negative regulation of T cell activation (GO:0050868)

GO Molecular Function (8): A2-type glycerophospholipase activity (GO:0004623), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), heparin binding (GO:0008201), heparan sulfate proteoglycan binding (GO:0043395), obsolete calcium-dependent phospholipase A2 activity (GO:0047498), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (1): extracellular region (GO:0005576)

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
glycerophospholipid metabolic process	3
lipid metabolic process	2
CD4-positive, alpha-beta T cell differentiation	1
regulatory T cell differentiation	1
acute inflammatory response to antigenic stimulus	1
regulation of acute inflammatory response	1
regulation of inflammatory response to antigenic stimulus	1
organophosphate metabolic process	1
defense response	1
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
primary metabolic process	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
metal ion binding	1
lipid binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
proteoglycan binding	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G2D	PLA2G3	Q9NZ20	968
PLA2G2D	PLA2R1	Q13018	911
PLA2G2D	PLA2G12A	Q9BZM1	898
PLA2G2D	PLA2G4A	P47712	692
PLA2G2D	PLA2G6	O60733	618
PLA2G2D	GANAB	Q14697	610
PLA2G2D	ENPP2	Q13822	534
PLA2G2D	PLA2G12B	Q9BX93	532
PLA2G2D	A0A2R8Y471	A0A2R8Y471	528
PLA2G2D	PLA2G15	Q8NCC3	516
PLA2G2D	PLA2G4C	Q9UP65	506
PLA2G2D	PLAAT3	P53816	496
PLA2G2D	PLA2G7	Q13093	475
PLA2G2D	Q3SX90	Q3SX90	474
PLA2G2D	GPC1	P35052	444

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PLA2G2D	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): DCAF8 (Affinity Capture-MS), NDUFA2 (Affinity Capture-MS), MMADHC (Affinity Capture-MS), NMB (Affinity Capture-MS), PPM1A (Affinity Capture-MS), DCAF6 (Affinity Capture-MS), NUCB1 (Affinity Capture-MS), NUCB2 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), HEXA (Affinity Capture-MS), COL6A1 (Affinity Capture-MS), LONP1 (Affinity Capture-MS), CUL4A (Affinity Capture-MS), CAMK1 (Affinity Capture-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

486 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20114257:CAG:C	acceptor_gain	1.0000
1:20114260:C:CC	acceptor_gain	1.0000
1:20115505:A:AC	donor_gain	1.0000
1:20115506:C:CC	donor_gain	1.0000
1:20115506:CAG:C	donor_gain	1.0000
1:20116498:C:CT	acceptor_gain	1.0000
1:20116499:A:T	acceptor_gain	1.0000
1:20116491:C:T	acceptor_gain	0.9900
1:20116492:A:T	acceptor_gain	0.9900
1:20119454:CTCA:C	donor_loss	0.9900
1:20119455:TCA:T	donor_loss	0.9900
1:20119456:CAC:C	donor_loss	0.9900
1:20119457:ACCAG:A	donor_gain	0.9900
1:20119458:C:A	donor_loss	0.9900
1:20119458:CCAGC:C	donor_gain	0.9900
1:20114256:TCAG:T	acceptor_gain	0.9800
1:20114257:CAGC:C	acceptor_gain	0.9800
1:20114258:AG:A	acceptor_gain	0.9800
1:20115506:CAGCA:C	donor_gain	0.9800
1:20116498:C:T	acceptor_gain	0.9800
1:20119453:ACT:A	donor_loss	0.9800
1:20119457:A:AC	donor_gain	0.9800
1:20119458:C:CC	donor_gain	0.9800
1:20119458:CCAG:C	donor_gain	0.9800
1:20114255:GTCAG:G	acceptor_gain	0.9700
1:20115498:CGTA:C	donor_loss	0.9700
1:20115499:GTAC:G	donor_loss	0.9700
1:20115500:TAC:T	donor_loss	0.9700
1:20115501:A:AC	donor_gain	0.9700
1:20115502:C:CC	donor_gain	0.9700

AlphaMissense

950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:20115608:C:G	C64S	0.975
1:20115609:A:T	C64S	0.975
1:20114217:T:A	D112V	0.973
1:20114226:C:G	C109S	0.973
1:20114227:A:T	C109S	0.973
1:20116337:C:G	D61H	0.971
1:20116346:C:G	D58H	0.971
1:20116335:G:C	D61E	0.969
1:20116335:G:T	D61E	0.969
1:20116375:C:G	C48S	0.967
1:20116376:A:T	C48S	0.967
1:20116381:C:G	C46S	0.967
1:20116382:A:T	C46S	0.967
1:20115563:C:G	C79S	0.965
1:20115564:A:T	C79S	0.965
1:20114217:T:G	D112A	0.964
1:20116336:T:A	D61V	0.964
1:20116344:A:C	D58E	0.963
1:20116344:A:T	D58E	0.963
1:20116385:C:A	G45C	0.963
1:20115611:C:G	C63S	0.962
1:20115612:A:T	C63S	0.962
1:20114199:C:G	C118S	0.961
1:20114200:A:T	C118S	0.961
1:20114139:C:G	C138S	0.959
1:20114140:A:T	C138S	0.959
1:20115509:C:G	C97S	0.959
1:20115510:A:T	C97S	0.959
1:20114220:C:G	C111S	0.958
1:20114221:A:T	C111S	0.958

dbSNP variants (sampled 300 via entrez): RS1000339247 (1:20115176 T>C), RS1000373366 (1:20120134 G>A), RS1000777142 (1:20113708 A>G), RS1000845743 (1:20119190 A>C), RS1001301875 (1:20114783 A>AC), RS1001363222 (1:20118917 T>C), RS1001432490 (1:20120187 GTC>G,GTCTC,GTCTCTC), RS1002195831 (1:20119161 G>C), RS1002313585 (1:20119471 C>T), RS1002669379 (1:20111555 G>A,C), RS1002704846 (1:20113981 T>C,G), RS1002852394 (1:20118844 C>G,T), RS1002977248 (1:20116082 A>C), RS1003302589 (1:20115267 C>G), RS1003318464 (1:20120654 C>A,G)

Disease associations

OMIM: gene MIM:605630 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_389	Obesity-related traits	7.000000e-06
GCST008260_11	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	1.000000e-11
GCST008260_8	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	2.000000e-26
GCST010577_15	Crohn’s disease	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4281 (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

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

pChembl	Type	Value	Unit	Molecule
8.15	IC50	7	nM	CHEMBL515637
7.46	IC50	35	nM	CHEMBL446349
7.25	IC50	56	nM	CHEMBL4593409
7.22	IC50	60	nM	VARESPLADIB
7.10	IC50	80	nM	CHEMBL514705
7.10	IC50	80	nM	CHEMBL514841
6.94	IC50	114	nM	VARESPLADIB
6.92	IC50	120	nM	CHEMBL148649
6.88	IC50	131	nM	VARESPLADIB
6.77	IC50	170	nM	CHEMBL514692
6.77	IC50	170	nM	CHEMBL506485
6.30	IC50	500	nM	CHEMBL504813
6.16	IC50	700	nM	CHEMBL479251
5.82	IC50	1500	nM	CHEMBL1159972
5.77	IC50	1700	nM	CHEMBL31185
5.62	IC50	2400	nM	CHEMBL33408
5.41	IC50	3900	nM	CHEMBL34162
5.35	IC50	4500	nM	CHEMBL280817

PubChem BioAssay actives

14 with measured affinity, of 42 total; 11 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	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.0070	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	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.0350	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxyacetic acid	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.0600	uM
2-[1-benzyl-2-(2-methylpropyl)-3-oxamoylbenzo[g]indol-4-yl]oxyacetic acid	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.0800	uM
2-(1-benzyl-2-ethyl-4-methoxybenzo[g]indol-3-yl)-2-oxoacetamide	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.0800	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxypropanoic acid	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.1200	uM
2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-(2-methylpropyl)benzo[g]indol-3-yl]-2-oxoacetamide	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.1700	uM
2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-ethylindol-3-yl]-2-oxoacetamide	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.1700	uM
2-[1-benzyl-2-(2-methylpropyl)-3-oxamoylindol-4-yl]oxyacetic acid	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.5000	uM
2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-(2-methylpropyl)indol-3-yl]-2-oxoacetamide	341243: Inhibition of human group2D phospholipase A2 by [3H]oleic acid-labeled Escherichia coli membrane assay	ic50	0.7000	uM

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
ICG 001	increases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Copper	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	decreases expression	1
Cadmium Chloride	increases abundance, decreases expression	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
CHEMBL802918	Binding	Compound was measured for the inhibitory activity against Secretory phospholipase A 2 (s-PLA2)	Novel frameworks for trifluoromethyl ketone and phosphonate tsa inhibitors of type II PLA2 — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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