PLA2G15

Summary

PLA2G15 (phospholipase A2 group XV, HGNC:17163) is a protein-coding gene on chromosome 16q22.1, encoding Lysosomal phospholipase A and acyltransferase (Q8NCC3). Has dual calcium-independent phospholipase and O-acyltransferase activities with a potential role in glycerophospholipid homeostasis and remodeling of acyl groups of lipophilic alcohols present in acidic cellular compartments.

Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. The protein encoded by this gene hydrolyzes lysophosphatidylcholine to glycerophosphorylcholine and a free fatty acid. This enzyme is present in the plasma and thought to be associated with high-density lipoprotein. A later paper contradicts the function of this gene. It demonstrates that this gene encodes a lysosomal enzyme instead of a lysophospholipase and has both calcium-independent phospholipase A2 and transacylase activities.

Source: NCBI Gene 23659 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 73 total
• Druggable target: yes
• MANE Select transcript: NM_012320

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17163
Approved symbol	PLA2G15
Name	phospholipase A2 group XV
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	LLPL, GXVPLA2
Ensembl gene	ENSG00000103066
Ensembl biotype	protein_coding
OMIM	609362
Entrez	23659

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000219345, ENST00000413021, ENST00000444212, ENST00000562449, ENST00000562966, ENST00000564827, ENST00000565460, ENST00000565744, ENST00000566188, ENST00000566978, ENST00000568082, ENST00000568599, ENST00000893628, ENST00000893629, ENST00000893630, ENST00000893631, ENST00000893632, ENST00000915915, ENST00000960258, ENST00000960259, ENST00000960260, ENST00000960261, ENST00000960262, ENST00000960263

RefSeq mRNA: 2 — MANE Select: NM_012320 NM_001363551, NM_012320

CCDS: CCDS10864, CCDS92182

Canonical transcript exons

ENST00000219345 — 6 exons

Exon	Start	End
ENSE00000691853	68255766	68255990
ENSE00002310182	68245373	68245553
ENSE00002581068	68259146	68261058
ENSE00003533649	68254919	68255037
ENSE00003591287	68255282	68255380
ENSE00003644749	68249290	68249446

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 92.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.8541 / max 233.9547, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154725	21.5778	1801
154724	1.2763	920

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	92.79	gold quality
apex of heart	UBERON:0002098	92.23	gold quality
muscle of leg	UBERON:0001383	91.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.47	gold quality
heart left ventricle	UBERON:0002084	89.37	gold quality
cardiac ventricle	UBERON:0002082	88.87	gold quality
metanephros cortex	UBERON:0010533	88.13	gold quality
right atrium auricular region	UBERON:0006631	87.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.86	gold quality
muscle organ	UBERON:0001630	86.82	gold quality
skeletal muscle organ	UBERON:0014892	86.82	gold quality
stromal cell of endometrium	CL:0002255	86.74	gold quality
cerebellar hemisphere	UBERON:0002245	86.60	gold quality
cerebellar cortex	UBERON:0002129	86.45	gold quality
heart	UBERON:0000948	86.30	gold quality
cardiac atrium	UBERON:0002081	86.23	gold quality
gluteal muscle	UBERON:0002000	85.89	gold quality
right lobe of liver	UBERON:0001114	85.88	gold quality
monocyte	CL:0000576	85.05	gold quality
spleen	UBERON:0002106	84.79	gold quality
cerebellum	UBERON:0002037	84.67	gold quality
mononuclear cell	CL:0000842	84.42	gold quality
leukocyte	CL:0000738	84.35	gold quality
adult mammalian kidney	UBERON:0000082	84.16	gold quality
right coronary artery	UBERON:0001625	83.87	gold quality
right lobe of thyroid gland	UBERON:0001119	83.73	gold quality
upper lobe of left lung	UBERON:0008952	83.63	gold quality
left lobe of thyroid gland	UBERON:0001120	83.61	gold quality
thoracic aorta	UBERON:0001515	83.59	gold quality
descending thoracic aorta	UBERON:0002345	83.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	11.28
E-ANND-3	yes	8.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting PLA2G15, 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-10401-5P	99.99	65.79	948
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4270	99.02	66.26	1987

Literature-anchored findings (GeneRIF, showing 7)

• The RXR agonist methoprene acid worked as well as all-trans-retinoic acid at increasing both lysosomal phospholipase A2 mRNA and enzyme activity (PMID:14754907)
• analyzed the association of five polymorphisms (-1357G>A, -403T>C, Arg92His, Ile198Thr, Ala379Val) and related haplotypes at the PLA2G7 locus with angiographic coronary artery disease, plasma LpPLA2 activity, and long-term survival (PMID:18983494)
• Patients with transient ischemic atack have a high-risk mechanism (large vessel stenosis or cardioembolism) or will experience stroke/death within 90 days. In contrast to CRP, both Lp-PLA(2) mass and activity were associated with this composite end point. (PMID:19461040)
• findings show that endosomal lipases participate in lipid antigen presentation by processing lipid antigens and have a role in T cell immunity against mycobacteria (PMID:27662254)
• Expression of the NFATC3-PLA2G15 chimera correlated with aggressive disease biology in murine patient-derived T-ALL xenografts, and poor prognosis in human T-ALL patients. (PMID:29330284)
• Zn(2+) was found to inhibit the esterase activity of LPLA2 in a noncompetitive manner exclusively at a neutral pH (between 6.5 and 8.0). Because lysosomes are reservoirs of Zn(2+) in cells, the pH optimum of LPLA2 might allow it to catalyze acyl transfer unimpeded within the organelle. (PMID:30830753)
• Phospholipase A2 group XV activity during cardiopulmonary bypass surgery. (PMID:33307060)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pla2g15	ENSDARG00000103271
mus_musculus	Pla2g15	ENSMUSG00000031903
rattus_norvegicus	Pla2g15	ENSRNOG00000019859
drosophila_melanogaster	CG18858	FBGN0042175
drosophila_melanogaster	CG31683	FBGN0051683
caenorhabditis_elegans	plag-15	WBGENE00010872

Paralogs (1): LCAT (ENSG00000213398)

Protein

Protein identifiers

Lysosomal phospholipase A and acyltransferase — Q8NCC3 (reviewed: Q8NCC3)

Alternative names: 1-O-acylceramide synthase, LCAT-like lysophospholipase, Lysophospholipase 3, Lysosomal phospholipase A2, Phospholipase A2 group XV

All UniProt accessions (7): Q8NCC3, B4DJW4, B4DPU0, H3BM47, H3BMU8, H3BPT3, H3BT70

UniProt curated annotations — full annotation on UniProt →

Function. Has dual calcium-independent phospholipase and O-acyltransferase activities with a potential role in glycerophospholipid homeostasis and remodeling of acyl groups of lipophilic alcohols present in acidic cellular compartments. Catalyzes hydrolysis of the ester bond of the fatty acyl group attached at sn-1 or sn-2 position of phospholipids (phospholipase A1 or A2 activity) and transfer it to the hydroxyl group at the first carbon of lipophilic alcohols (O-acyltransferase activity). Among preferred fatty acyl donors are phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols and phosphatidylserines. Favors sn-2 over sn-1 deacylation of unsaturated fatty acyl groups of phosphatidylcholines, phosphatidylethanolamines, and phosphatidylglycerols. Among preferred fatty acyl acceptors are natural lipophilic alcohols including short-chain ceramide N-acetyl-sphingosine (C2 ceramide), alkylacylglycerols, monoacylglycerols, and acylethanolamides such as anandamide and oleoylethanolamide. Selectively hydrolyzes the sn-1 fatty acyl group of truncated oxidized phospholipids and may play a role in detoxification of reactive oxidized phospholipids during oxidative stress. Required for normal phospholipid degradation in alveolar macrophages with potential implications in the clearance of pulmonary surfactant, which is mainly composed of dipalmitoylphosphatidylcholine (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine). Involved in the first step of bis(monoacylglycero)phosphate (BMP) de novo synthesis from phosphatidylglycerol (1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol), PG). BMP is an important player in cargo sorting and degradation, regulation of cellular cholesterol levels and intercellular communication. At neutral pH, hydrolyzes the sn-1 fatty acyl group of the lysophosphatidylcholines.

Subcellular location. Lysosome. Secreted. Membrane.

Tissue specificity. Detected in blood plasma (at protein level). Ubiquitous. Highly expressed in heart, placenta, skeletal muscle, kidney and pancreas. Detected at lower levels in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.

Post-translational modifications. N-glycosylated. N-glycosylation is important for maturation of the enzyme and normal subcellular location.

Activity regulation. Inhibited by zinc ions at neutral pH. Zinc ions in plasma may keep the enzyme from hydrolyzing inappropriate substrates.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NCC3-1	1	yes
Q8NCC3-2	2

RefSeq proteins (2): NP_001350480, NP_036452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003386	LACT/PDAT_acylTrfase	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF02450

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), 12 shown:

• a 1-acyl-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + a fatty acid + H(+) (RHEA:15177)
• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:15801)
• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:18689)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + N-(acetyl)-sphing-4-enine = 1-(9Z-octadecenoyl)-N-(acetyl)-sphing-4-enine + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38703)
• 1-O-hexadecyl-2-acetyl-sn-glycerol + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine = 1-O-hexadecyl-2-acetyl-3-(9Z)-octadecenoyl-sn-glycerol + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38707)
• 1-O-hexadecylglycerol + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine = 1-O-hexadecyl-3-(9Z)-octadecenoylglycerol + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38711)
• 1-O-hexadecyl-2-O-methyl-sn-glycerol + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine = 1-O-hexadecyl-2-O-methyl-3-(9Z)-octadecenoyl-sn-glycerol + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38723)
• 1-hexadecanoyl-sn-glycerol + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine = 1-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38727)
• 3-hexadecanoyl-sn-glycerol + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine = 1-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38731)
• 2-hexadecanoylglycerol + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine = 1-(9Z)-octadecenoyl-2-hexadecanoylglycerol + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38735)
• 1-(9Z-octadecenoyl)-sn-glycerol + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine = 1,3-di-(9Z-octadecenoyl)-glycerol + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38739)
• 3-(9Z-octadecenoyl)-sn-glycerol + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine = 1,3-di-(9Z-octadecenoyl)-glycerol + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:38743)

UniProt features (72 total): helix 19, strand 17, mutagenesis site 11, binding site 6, turn 5, glycosylation site 4, active site 3, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
4X90	X-RAY DIFFRACTION	1.84
6MTW	X-RAY DIFFRACTION	2
4X91	X-RAY DIFFRACTION	2.3
4X93	X-RAY DIFFRACTION	2.6
4X97	X-RAY DIFFRACTION	2.65
4X94	X-RAY DIFFRACTION	2.7
4X92	X-RAY DIFFRACTION	3
4X95	X-RAY DIFFRACTION	3.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCC3-F1	93.81	0.89

Functional residue map

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

Catalytic / active sites (3): 198 (acyl-ester intermediate); 360 (charge relay system); 392 (charge relay system)

Ligand- & substrate-binding residues (6): 392; 46; 198; 199; 340; 355

Disulfide bonds (1): 65–89

Glycosylation sites (4): 99, 273, 289, 398

Mutagenesis-validated functional residues (11):

Position	Phenotype
46	decreases membrane binding, phospholipase and transacylase activity at acidic ph.
46	has no effect on membrane binding or transacylase activity at acidic ph. increases membrane binding and transacylase act
83	no effect on phospholipase activity. strongly decreases transacylase activity and association with membranes.
85	no effect on phospholipase activity. strongly decreases transacylase activity and association with membranes.
99	loss of glycosylation site. leads to retention in the endoplasmic reticulum and nearly abolishes the production of the m
198	abolishes phospholipase and transacylase activity. abolishes association with membranes.
235	no effect on phospholipase activity. abolishes transacylase activity. has no effect on association with membranes.
273	loss of glycosylation site. mildly reduces production of the mature, active enzyme.
289	loss of glycosylation site. mildly reduces production of the mature, active enzyme.
362	no effect on phospholipase activity. strongly decreases transacylase activity and abolishes association with membranes.
398	loss of glycosylation site. slightly reduces production of the mature, active enzyme.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483115	Hydrolysis of LPC

MSigDB gene sets: 227 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, chr16q22, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KEGG_LYSOSOME, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (13): phospholipid metabolic process (GO:0006644), glycerophospholipid metabolic process (GO:0006650), diacylglycerol biosynthetic process (GO:0006651), phosphatidylserine metabolic process (GO:0006658), ceramide metabolic process (GO:0006672), fatty acid catabolic process (GO:0009062), phosphatidylcholine catabolic process (GO:0034638), phosphatidylethanolamine catabolic process (GO:0046338), phosphatidylcholine metabolic process (GO:0046470), phosphatidylglycerol metabolic process (GO:0046471), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), lipid catabolic process (GO:0016042)

GO Molecular Function (13): phosphatidylcholine lysophospholipase A1 activity (GO:0004622), phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), obsolete O-acyltransferase activity (GO:0008374), glycerophospholipid phospholipase A1 activity (GO:0008970), acylglycerol O-acyltransferase activity (GO:0016411), obsolete calcium-independent phospholipase A2 activity (GO:0047499), A2-type glycerophospholipase activity (GO:0004623), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), lysosome (GO:0005764), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	3
glycerophospholipid metabolic process	3
cellular anatomical structure	3
glycerophospholipid catabolic process	2
catalytic activity	2
organophosphate metabolic process	1
phospholipid metabolic process	1
glycerolipid metabolic process	1
diacylglycerol metabolic process	1
acylglycerol biosynthetic process	1
modified amino acid metabolic process	1
sphingolipid metabolic process	1
fatty acid metabolic process	1
lipid catabolic process	1
monocarboxylic acid catabolic process	1
phosphatidylcholine metabolic process	1
phosphatidylethanolamine metabolic process	1
primary metabolic process	1
monocarboxylic acid metabolic process	1
catabolic process	1
lysophospholipase A1 activity	1
lipid binding	1
transition metal ion binding	1
A1-type glycerophospholipase activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
binding	1
transferase activity	1
cation binding	1
nuclear lumen	1
lytic vacuole	1
extracellular vesicle	1

Protein interactions and networks

STRING

1364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G15	PLAAT3	P53816	640
PLA2G15	PLA2G7	Q13093	612
PLA2G15	PLA2G6	O60733	603
PLA2G15	PLA2G2A	P14555	576
PLA2G15	PLA2G3	Q9NZ20	570
PLA2G15	PLA2G4A	P47712	565
PLA2G15	PLA2G2D	Q9UNK4	516
PLA2G15	PLA2G10	O15496	492
PLA2G15	PLA2G5	P39877	477
PLA2G15	PNPLA4	P41247	471
PLA2G15	PNPLA6	Q8IY17	450
PLA2G15	POU2F3	Q9UKI9	438
PLA2G15	PLA2G4C	Q9UP65	429
PLA2G15	PAFAH2	Q99487	419
PLA2G15	PLA2G4D	Q86XP0	404

IntAct

14 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PLA2G15	CCT6A	psi-mi:“MI:0915”(physical association)	0.500
	VPS37C	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
IGF2R	MANBA	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350
PLA2G15	TCP1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
FBXO6	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PLA2G15	IMMT	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): PLA2G15 (Affinity Capture-RNA), PLA2G15 (Affinity Capture-MS), IMMT (Two-hybrid), PLA2G15 (Affinity Capture-MS), PLA2G15 (Affinity Capture-RNA), CCT6A (Affinity Capture-MS), PLA2G15 (Affinity Capture-MS), PLA2G15 (Affinity Capture-MS), PLA2G15 (Affinity Capture-MS), PLA2G15 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), TCP1 (Affinity Capture-MS), PLA2G15 (Affinity Capture-MS)

ESM2 similar proteins: F1NZI4, O00754, O09008, O35082, O35795, O46432, O55026, O89023, O97583, P04062, P10696, P11117, P16301, P17405, P17439, P18424, P20611, P21139, P24638, P24823, P52849, P52850, P53761, P58242, Q04519, Q0P5F0, Q0V8B6, Q0VD19, Q2KHZ8, Q4R5N9, Q5NVF6, Q5R8E3, Q5RFU0, Q6XPZ3, Q6YGZ1, Q6ZNF0, Q70KH2, Q71RP1, Q8BP56, Q8BX37

Diamond homologs: O35502, O35573, O35724, O35840, P04180, P16301, P18424, P30930, P53760, P53761, Q08758, Q675A5, Q6XPZ3, Q8NCC3, Q8VEB4, Q8WMP9, Q9FZI8, P40345, Q10PI6, Q4VCM1, Q9FYC7, Q9FNA9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

963 predictions. Top by Δscore:

Variant	Effect	Δscore
16:68245530:G:GT	donor_gain	1.0000
16:68245554:G:GG	donor_gain	1.0000
16:68249288:A:AG	acceptor_gain	1.0000
16:68249289:G:GT	acceptor_gain	1.0000
16:68249289:GTCC:G	acceptor_gain	1.0000
16:68255276:CTACA:C	acceptor_loss	1.0000
16:68255277:TACA:T	acceptor_loss	1.0000
16:68255278:ACAGG:A	acceptor_loss	1.0000
16:68255279:CAGGT:C	acceptor_loss	1.0000
16:68255280:A:AT	acceptor_loss	1.0000
16:68255381:G:GG	donor_gain	1.0000
16:68255764:A:AG	acceptor_gain	1.0000
16:68255765:G:GG	acceptor_gain	1.0000
16:68255988:CAGGT:C	donor_loss	1.0000
16:68255990:GGTAA:G	donor_loss	1.0000
16:68255991:G:GG	donor_gain	1.0000
16:68259143:CAGGA:C	acceptor_loss	1.0000
16:68259144:A:AG	acceptor_gain	1.0000
16:68259144:AG:A	acceptor_gain	1.0000
16:68259145:G:GT	acceptor_gain	1.0000
16:68259145:GG:G	acceptor_gain	1.0000
16:68259145:GGA:G	acceptor_gain	1.0000
16:68259145:GGAGA:G	acceptor_gain	1.0000
16:68245546:G:GA	donor_gain	0.9900
16:68245549:GCTGG:G	donor_gain	0.9900
16:68245552:GG:G	donor_gain	0.9900
16:68245553:GG:G	donor_gain	0.9900
16:68245553:GGT:G	donor_loss	0.9900
16:68245555:T:A	donor_loss	0.9900
16:68245560:C:T	donor_gain	0.9900

AlphaMissense

2660 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:68249388:T:A	W76R	0.998
16:68249388:T:C	W76R	0.998
16:68255365:T:A	W163R	0.997
16:68255365:T:C	W163R	0.997
16:68249355:T:A	C65S	0.996
16:68249356:G:C	C65S	0.996
16:68255368:C:A	R164S	0.996
16:68255369:G:C	R164P	0.996
16:68255856:G:T	S198I	0.996
16:68249314:T:C	L51P	0.995
16:68249427:T:A	C89S	0.995
16:68249428:G:C	C89S	0.995
16:68249430:T:A	W90R	0.995
16:68249430:T:C	W90R	0.995
16:68249390:G:C	W76C	0.994
16:68249390:G:T	W76C	0.994
16:68249427:T:C	C89R	0.994
16:68255367:G:C	W163C	0.994
16:68255367:G:T	W163C	0.994
16:68249309:C:A	N49K	0.993
16:68249309:C:G	N49K	0.993
16:68249319:G:C	A53P	0.993
16:68249355:T:C	C65R	0.993
16:68249356:G:A	C65Y	0.993
16:68249357:C:G	C65W	0.993
16:68249428:G:A	C89Y	0.993
16:68249392:T:C	L77P	0.992
16:68259517:A:C	S367R	0.991
16:68259519:T:A	S367R	0.991
16:68259519:T:G	S367R	0.991

dbSNP variants (sampled 300 via entrez): RS1000104782 (16:68257125 G>A), RS1000196353 (16:68256895 G>T), RS1000289923 (16:68256361 A>G), RS1000556318 (16:68261290 G>A), RS1000662083 (16:68254522 T>C), RS1000682275 (16:68254862 G>T), RS1001274115 (16:68248551 A>G), RS1001298492 (16:68257417 T>C), RS1001307906 (16:68250441 T>G), RS1001409934 (16:68248837 G>A), RS1001447951 (16:68251075 G>A,T), RS1002009137 (16:68260845 C>T), RS1002104180 (16:68261134 G>A), RS1002124779 (16:68254004 T>C), RS1002226238 (16:68244211 A>G)

Disease associations

OMIM: gene MIM:609362 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002539_84	Schizophrenia	2.000000e-08
GCST003680_17	C-reactive protein levels or HDL-cholesterol levels (pleiotropy)	2.000000e-23
GCST004600_135	Eosinophil percentage of white cells	4.000000e-09
GCST004606_19	Eosinophil count	6.000000e-10
GCST006803_42	Schizophrenia	4.000000e-08
GCST010002_113	Refractive error	2.000000e-14
GCST010989_15	Body size at age 10	8.000000e-09
GCST012020_156	Serum metabolite levels	2.000000e-12
GCST012021_81	Serum metabolite levels	2.000000e-12
GCST90020029_575	Waist circumference adjusted for body mass index	5.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4986 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
Acetaminophen	increases expression	2
pirinixic acid	affects binding, decreases expression, increases activity	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Amiodarone	affects expression	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Rotenone	increases expression	1
Silicon Dioxide	increases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Okadaic Acid	increases expression	1
Sodium Benzoate	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209102	Binding	Inhibition of LYPLA3 binding to FP-biotin in [12C][14N]-lysine, arginine and [13C6][15N2]-lysine, arginine labeled HEK293T cells at 20 uM after 1 hr by isotopic activity-based protein profiling-MudPIT assay	Discovery and optimization of sulfonyl acrylonitriles as selective, covalent inhibitors of protein phosphatase methylesterase-1. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2B1	Abcam HeLa PLA2G15 KO	Cancer cell line	Female
CVCL_TE07	HAP1 PLA2G15 (-) 1	Cancer cell line	Male
CVCL_TE08	HAP1 PLA2G15 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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