PLA2G4C

Summary

PLA2G4C (phospholipase A2 group IVC, HGNC:9037) is a protein-coding gene on chromosome 19q13.33, encoding Cytosolic phospholipase A2 gamma (Q9UP65). Calcium-independent phospholipase, lysophospholipase and O-acyltransferase involved in phospholipid remodeling with implications in endoplasmic reticulum membrane homeostasis and lipid droplet biogenesis.

This gene encodes a protein which is a member of the phospholipase A2 enzyme family which hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids, both of which serve as precursors in the production of signaling molecules. The encoded protein has been shown to be a calcium-independent and membrane bound enzyme. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8605 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 126 total
• Druggable target: yes
• MANE Select transcript: NM_003706

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9037
Approved symbol	PLA2G4C
Name	phospholipase A2 group IVC
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	cPLA2-gamma
Ensembl gene	ENSG00000105499
Ensembl biotype	protein_coding
OMIM	603602
Entrez	8605

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 26 protein_coding, 8 retained_intron, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000354276, ENST00000593765, ENST00000594156, ENST00000594790, ENST00000595161, ENST00000595487, ENST00000595899, ENST00000596138, ENST00000596352, ENST00000596353, ENST00000596510, ENST00000597377, ENST00000597713, ENST00000598185, ENST00000598457, ENST00000598488, ENST00000598813, ENST00000599063, ENST00000599111, ENST00000599239, ENST00000599300, ENST00000599921, ENST00000600170, ENST00000601946, ENST00000887089, ENST00000887090, ENST00000887091, ENST00000887092, ENST00000887093, ENST00000887094, ENST00000887095, ENST00000887096, ENST00000887097, ENST00000951718, ENST00000951719, ENST00000951720, ENST00000951721, ENST00000951722, ENST00000951723, ENST00000951724, ENST00000951725, ENST00000951726

RefSeq mRNA: 3 — MANE Select: NM_003706 NM_001159322, NM_001159323, NM_003706

CCDS: CCDS12710, CCDS54286, CCDS59403

Canonical transcript exons

ENST00000599921 — 17 exons

Exon	Start	End
ENSE00000717816	48090364	48090417
ENSE00000717823	48074767	48074874
ENSE00003215750	48110487	48110817
ENSE00003477982	48054878	48055049
ENSE00003489683	48099671	48099860
ENSE00003505169	48052997	48053147
ENSE00003513094	48088686	48088712
ENSE00003560177	48105333	48105444
ENSE00003562409	48085059	48085112
ENSE00003563888	48106522	48106561
ENSE00003564890	48077771	48077824
ENSE00003596831	48098139	48098259
ENSE00003609418	48061998	48062152
ENSE00003614426	48095464	48095604
ENSE00003621138	48067791	48067886
ENSE00003644728	48104588	48104724
ENSE00003674371	48047846	48048388

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 97.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7705 / max 194.1457, expressed in 1199 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181814	5.0918	967
181812	1.6754	469
181815	0.8177	448
181811	0.5708	189
181813	0.4655	290
181810	0.0779	37
181816	0.0715	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gluteal muscle	UBERON:0002000	97.53	gold quality
inferior vagus X ganglion	UBERON:0005363	96.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.51	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.25	gold quality
vastus lateralis	UBERON:0001379	96.05	gold quality
corpus callosum	UBERON:0002336	96.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.01	gold quality
apex of heart	UBERON:0002098	95.97	gold quality
quadriceps femoris	UBERON:0001377	95.96	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.92	gold quality
cerebellar hemisphere	UBERON:0002245	95.88	gold quality
cerebellar cortex	UBERON:0002129	95.81	gold quality
skeletal muscle tissue	UBERON:0001134	95.79	gold quality
triceps brachii	UBERON:0001509	95.68	gold quality
spinal cord	UBERON:0002240	95.55	gold quality
substantia nigra	UBERON:0002038	95.39	gold quality
muscle organ	UBERON:0001630	95.35	gold quality
gastrocnemius	UBERON:0001388	95.24	gold quality
oocyte	CL:0000023	95.23	gold quality
midbrain	UBERON:0001891	95.21	gold quality
muscle of leg	UBERON:0001383	95.17	gold quality
cerebellum	UBERON:0002037	95.17	gold quality
lateral globus pallidus	UBERON:0002476	95.16	gold quality
right frontal lobe	UBERON:0002810	94.99	gold quality
deltoid	UBERON:0001476	94.98	gold quality
inferior olivary complex	UBERON:0002127	94.98	gold quality
putamen	UBERON:0001874	94.79	gold quality
subthalamic nucleus	UBERON:0001906	94.73	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.57	gold quality
nucleus accumbens	UBERON:0001882	94.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

26 targeting PLA2G4C, 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-3617-3P	99.98	67.86	918
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-610	96.84	67.98	905
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-3651	95.62	64.67	287
HSA-MIR-492	94.02	64.46	413
HSA-MIR-328-3P	92.82	64.37	521

Literature-anchored findings (GeneRIF, showing 22)

• Novel PLA2G4C polymorphism as a molecular diagnostic A minisatellite polymorphism in the untranslated region of exon 1, with allelic variants that have one, two or three 27-bp repeats (PMID:11958371)
• Enzymatic properties of human cytosolic phospholipase A(2)gamma. (PMID:12039969)
• TNF-alpha & IFN-gamma induce gene expression of a novel cytosolic PLA(2) IVC in human airway epithelial cells. The possibility that it is involved in cytokine-mediated inflammation in the respiratory tract is inferred. (PMID:12396716)
• Down-regulation of Phospholipase A2 is associated with colon tumorigenesis (PMID:15788676)
• identification of its remarkable substrate selectivity that results in the highly selective generation of 2-arachidonoyl lysophosphatidylcholine (PMID:15908428)
• results indicate that complete C-terminal processing is important for the functional expression of cPLA2, although not for its membrane localization (PMID:15944408)
• Caspase-3-dependent activation of calcium-independent phospholipase A2 enhances cell migration in non-apoptotic ovarian cancer cells (PMID:16882668)
• iPLA2gamma has roles in the lipid plasticity of myocardium, in generating signaling metabolites, and in modulating energy storage and utilization in myocardium in different metabolic contexts (PMID:17213206)
• Single nucleotide polymorphism is asociated with schizzophrenia in a Chinese population. (PMID:17417066)
• endometrial cell PGE2 biosynthesis was associated with PLA2G4C expression and activity (PMID:17459165)
• The subcellular localization and enzymatic properties of cPLA2gamma with C-terminal FLAG-tag, was examined. (PMID:19501189)
• locus showed a weak association with schizophrenia in a Chinese population (PMID:20016400)
• cPLA(2) has a role in the induction of cell autonomous cellular immunity to Chlamydia (PMID:20452986)
• Findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor. (PMID:21184677)
• these results suggest that cPLA(2)gamma plays an important role in cancer cell chemotaxis. (PMID:21600875)
• These findings suggest that IVC-PLA(2) is involved in regulations of macrophage differentiation and macrophage polarization. (PMID:22108055)
• site-specific cytosine methylation of the CpT of PLA2G4C may play a role in the pathogenesis of schizophrenia. (PMID:22878031)
• Results demonstrated no significant impact of PLA2G6 and PLA2G4C gene polymorphisms on attenuated niacin skin flushing in schizophrenia patients. (PMID:26160611)
• The A allele in PLA2G4C single nucleotide polymorphism (rs1549637) is associated with a worse prognosis in patients with colorectal cancer, especially in stage II. (PMID:26364726)
• Five single-nucleotide polymorphisms (SNPs) (rs9226, rs1045376, rs251684, rs2307279, and rs156631) in PLA2G4C and four SNPs (rs6533451, rs2285714, rs2285713, and rs11728699) in PLA2G12A were selected and genotyped. Our results showed a significant association between ASD and the rs251684 variant of PLA2G4C. The rs251684 polymorphism of PLA2G4C may be associated with Autism Spectrum Disorder risk. (PMID:27611910)
• We found no significant influence of the PLA2G6 and PLA2G4C polymorphisms on mean age at first hospital admission (P > 0.05) and that the investigated polymorphisms significantly influenced the clinical psychopathology only in male patients. The PLA2G4C polymorphism accounted for approximately 12% of negative symptom severity. (PMID:28651698)
• Association between PLA2 gene polymorphisms and treatment response to antipsychotic medications: A study of antipsychotic-naive first-episode psychosis patients and nonadherent chronic psychosis patients. (PMID:37290257)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:101699	ENSDARG00000033355
danio_rerio	si:ch73-55i23.1	ENSDARG00000042090
danio_rerio	pla2g4cl1	ENSDARG00000045982
danio_rerio	pla2g4c	ENSDARG00000101721
mus_musculus	Pla2g4c	ENSMUSG00000033847
rattus_norvegicus	Pla2g4c	ENSRNOG00000026764

Paralogs (5): PLA2G4A (ENSG00000116711), PLA2G4D (ENSG00000159337), PLA2G4F (ENSG00000168907), PLA2G4E (ENSG00000188089), PLA2G4B (ENSG00000243708)

Protein

Protein identifiers

Cytosolic phospholipase A2 gamma — Q9UP65 (reviewed: Q9UP65)

Alternative names: Cytosolic lysophospholipase, Cytosolic lysophospholipid O-acyltransferase, Phospholipase A2 group IVC

All UniProt accessions (9): Q9UP65, M0QX83, M0QY18, M0QZB1, M0R0F6, M0R0M8, M0R1B4, M0R339, M0R3I9

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-independent phospholipase, lysophospholipase and O-acyltransferase involved in phospholipid remodeling with implications in endoplasmic reticulum membrane homeostasis and lipid droplet biogenesis. Preferentially hydrolyzes the ester bond of the fatty acyl group attached at the sn-2 position of phospholipids with choline and ethanolamine head groups, producing lysophospholipids that are used in deacylation-reacylation cycles. Transfers the sn-1 fatty acyl from one lysophospholipid molecule to the sn-2 position of another lysophospholipid to form diacyl, alkylacyl and alkenylacyl glycerophospholipids. Cleaves ester bonds but not alkyl or alkenyl ether bonds at sn-1 position of lysophospholipids. Catalyzes sn-2 fatty acyl transfer from phospholipids to the sn-2 position of 1-O-alkyl or 1-O-alkenyl lysophospholipids with lower efficiency. In response to dietary fatty acids, may play a role in the formation of nascent lipid droplets from the endoplasmic reticulum likely by regulating the phospholipid composition of these organelles. (Microbial infection) May play a role in replication and assembly of human hepatitis C virus (HCV). In response to HCV infection, promotes remodeling of host endoplasmic reticulum membranes to form organelle-like structures called membranous web, where HCV replication occur. Can further mediate translocation of replication complexes to lipid droplets to enable virion assembly. (Microbial infection) May facilitate human T-lymphotropic virus type 1 (HTLV-1) infection by promoting leukotriene B4 (LTB4) biosynthesis. LTB4 acts as a chemoattractant for HTLV-1-infected CD4-positive T cells and favors cell to cell viral transmission.

Subunit / interactions. (Microbial infection) Interacts with HCV non-structural protein 4B/NS4B; this interaction likely initiates the recruitment of replication complexes to lipid droplets.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Mitochondrion membrane. Lipid droplet.

Tissue specificity. Highly expressed in heart and skeletal muscle.

Activity regulation. Not regulated by calcium, coenzyme A or ATP. Lysophospholipase activity is inhibited by palmitoyl-CoA. Lysophospholipase and O-acyltransferase activities are inhibited by methylarachidonoylfluorophosphonate. Lysophospholipase activity is inhibited by phosphatidate or lysophosphatidate. O-acyltransferase activity is up-regulated at low concentration (10-20 uM) of phosphatidate or lysophosphatidate, but inhibited at higher concentrations.

Induction. (Microbial infection) Up-regulated by HCV. (Microbial infection) Transcriptionally up-regulated by HTLV-1 Tax.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UP65-1	1	yes
Q9UP65-2	2
Q9UP65-3	3

RefSeq proteins (3): NP_001152794, NP_001152795, NP_003697* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002642	LysoPLipase_cat_dom	Domain
IPR016035	Acyl_Trfase/lysoPLipase	Homologous_superfamily

Pfam: PF01735

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-O-alkyl-2-acyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:36231)
• 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-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + hexadecanoate + H(+) (RHEA:40435)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:40571)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:40811)
• 2 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + sn-glycerol 3-phosphocholine (RHEA:40879)
• 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine + sn-glycerol 3-phosphocholine (RHEA:40899)
• 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:41067)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:41223)

UniProt features (32 total): sequence variant 12, mutagenesis site 6, sequence conflict 3, splice variant 2, active site 2, modified residue 2, chain 1, propeptide 1, domain 1, region of interest 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UP65-F1	83.99	0.68

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): 82 (nucleophile); 385 (proton acceptor)

Post-translational modifications (3): 337, 538, 538

Mutagenesis-validated functional residues (6):

Position	Phenotype
54	abolishes enzyme activity. reduces lipid droplet formation; when associated with a-82; a-385 and a-402.
82	abolishes enzyme activity. reduces lipid droplet formation; when associated with a-54; a-385 and a-402.
385	abolishes enzyme activity. reduces lipid droplet formation; when associated with a-54; a-82 and a-402.
402	abolishes enzyme activity. reduces lipid droplet formation; when associated with a-54; a-82 and a-385.
538–539	loss of prenylation.
538	has no effect on membrane localization. decreases the affinity for 1-o-hexadecyl-sn-glycero-3-phosphocholine acyl accept

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1482788	Acyl chain remodelling of PC
R-HSA-1482839	Acyl chain remodelling of PE
R-HSA-1482922	Acyl chain remodelling of PI
R-HSA-1483115	Hydrolysis of LPC
R-HSA-1483152	Hydrolysis of LPE

MSigDB gene sets: 199 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, CAIRO_HEPATOBLASTOMA_CLASSES_DN, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_PARTURITION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_ORGANELLE_ASSEMBLY, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (14): phospholipid metabolic process (GO:0006644), platelet activating factor biosynthetic process (GO:0006663), inflammatory response (GO:0006954), parturition (GO:0007567), arachidonate metabolic process (GO:0019369), intracellular signal transduction (GO:0035556), phosphatidylcholine acyl-chain remodeling (GO:0036151), phosphatidylethanolamine acyl-chain remodeling (GO:0036152), glycerophospholipid catabolic process (GO:0046475), lipid droplet formation (GO:0140042), lipid metabolic process (GO:0006629), glycerophospholipid metabolic process (GO:0006650), phospholipid catabolic process (GO:0009395), lipid catabolic process (GO:0016042)

GO Molecular Function (13): phosphatidylcholine lysophospholipase A1 activity (GO:0004622), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), calcium-dependent phospholipid binding (GO:0005544), obsolete O-acyltransferase activity (GO:0008374), glycerophospholipid phospholipase A1 activity (GO:0008970), obsolete calcium-dependent phospholipase A2 activity (GO:0047498), obsolete calcium-independent phospholipase A2 activity (GO:0047499), glycerophospholipase activity (GO:0004620), A2-type glycerophospholipase activity (GO:0004623), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (11): nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), membrane (GO:0016020), mitochondrial membrane (GO:0031966), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	5

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	3
lipid metabolic process	2
phosphatidylcholine metabolic process	2
phospholipid metabolic process	2
catalytic activity	2
endomembrane system	2
organelle membrane	2
cell periphery	2
intracellular membrane-bounded organelle	2
organophosphate metabolic process	1
ether lipid biosynthetic process	1
platelet activating factor metabolic process	1
glycerophospholipid biosynthetic process	1
defense response	1
multi-organism reproductive process	1
multi-multicellular organism process	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
intracellular anatomical structure	1
signal transduction	1
glycerophospholipid metabolic process	1
phospholipid catabolic process	1
glycerolipid catabolic process	1
lipid storage	1
lipid droplet organization	1
membraneless organelle assembly	1
primary metabolic process	1
glycerolipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
catabolic process	1
lysophospholipase A1 activity	1
metal ion binding	1
lipid binding	1
phospholipid binding	1
A1-type glycerophospholipase activity	1
phospholipase activity	1

Protein interactions and networks

STRING

788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G4C	PLA2G2A	P14555	571
PLA2G4C	PLA2G12A	Q9BZM1	570
PLA2G4C	PLA2G6	O60733	548
PLA2G4C	PNPLA8	Q9NP80	533
PLA2G4C	PLA2G2D	Q9UNK4	506
PLA2G4C	PSTPIP2	Q9H939	499
PLA2G4C	PLA2G2F	Q9BZM2	451
PLA2G4C	PLA2G10	O15496	449
PLA2G4C	DGAT1	O75907	447
PLA2G4C	PLA2G7	Q13093	446
PLA2G4C	PNPLA4	P41247	446
PLA2G4C	PLA2G12B	Q9BX93	435
PLA2G4C	PLA2G5	P39877	434
PLA2G4C	PLA1A	Q53H76	431
PLA2G4C	PLA2G15	Q8NCC3	429
PLA2G4C	PNPLA6	Q8IY17	429

IntAct

19 interactions, top by confidence:

A	B	Type	Score
PLA2G4C		psi-mi:“MI:0915”(physical association)	0.560
HTT	PLA2G4C	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (13): HCVgp1 (Affinity Capture-Western), PLA2G4C (Negative Genetic), PLA2G4C (Positive Genetic), PLA2G4C (Positive Genetic), PRKDC (Positive Genetic), PLA2G4C (Positive Genetic), PLA2G4C (Positive Genetic), PLA2G4C (Positive Genetic), PLA2G4C (Positive Genetic), S100A10 (Reconstituted Complex), PLA2G4C (Affinity Capture-RNA), PLA2G4C (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A2VE39, A4IFJ5, A4IHT9, A8K855, B1WAZ6, D2HRF1, O00763, O02697, O60551, O70310, O77793, P19447, P30419, P31717, P35574, P47712, P47713, P48736, P49147, P50392, P50393, Q0E908, Q2PQH8, Q2TBU5, Q4R6Y8, Q5R8A5, Q5R981, Q5U2Z5, Q5ZJT0, Q641K1, Q66HX8, Q6DD21, Q7K556, Q7T0T9, Q7XQT2, Q80YD1, Q811C2, Q8C5P5, Q8IYB8, Q8K1Q0

Diamond homologs: A4IFJ5, B1WAZ6, O77793, P47713, P49147, P50393, P53541, Q64GA5, Q7T0T9, Q9TT38, Q9UP65, A0JJX5, P0C869, P0C871, P47712, Q3MJ16, Q50L41, Q50L42, Q50L43, Q5R8A5, Q68DD2, Q86XP0, Q8L706, B6ETT4, P50392, Q7XA06, Q8RXU9, Q9C8H3, Q9SKR2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3338 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48053160:C:CT	acceptor_gain	1.0000
19:48053161:A:T	acceptor_gain	1.0000
19:48053166:A:T	acceptor_gain	1.0000
19:48061993:ATTAC:A	donor_loss	1.0000
19:48061994:TTACC:T	donor_loss	1.0000
19:48061995:TACCT:T	donor_loss	1.0000
19:48061996:A:T	donor_loss	1.0000
19:48062163:C:CT	acceptor_gain	1.0000
19:48062163:C:T	acceptor_gain	1.0000
19:48095459:CTGA:C	donor_loss	1.0000
19:48095460:TGA:T	donor_loss	1.0000
19:48095461:GA:G	donor_loss	1.0000
19:48095463:CC:C	donor_loss	1.0000
19:48095511:C:A	donor_gain	1.0000
19:48095603:CT:C	acceptor_gain	1.0000
19:48095605:C:CC	acceptor_gain	1.0000
19:48099664:GACTT:G	donor_loss	1.0000
19:48099665:ACTT:A	donor_loss	1.0000
19:48099667:TTACT:T	donor_loss	1.0000
19:48099668:TA:T	donor_loss	1.0000
19:48099669:A:AC	donor_gain	1.0000
19:48099669:ACTT:A	donor_gain	1.0000
19:48099670:C:CC	donor_gain	1.0000
19:48099670:CTT:C	donor_gain	1.0000
19:48099670:CTTC:C	donor_gain	1.0000
19:48099670:CTTCT:C	donor_gain	1.0000
19:48099856:TTGCC:T	acceptor_gain	1.0000
19:48099857:TGCC:T	acceptor_gain	1.0000
19:48099858:GCC:G	acceptor_gain	1.0000
19:48099859:CC:C	acceptor_gain	1.0000

AlphaMissense

3538 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48099706:A:G	W138R	0.996
19:48099706:A:T	W138R	0.996
19:48067824:A:G	W357R	0.994
19:48067824:A:T	W357R	0.994
19:48090412:A:G	W239R	0.991
19:48090412:A:T	W239R	0.991
19:48095519:G:C	F218L	0.991
19:48095519:G:T	F218L	0.991
19:48095521:A:G	F218L	0.991
19:48104589:A:G	W86R	0.991
19:48104589:A:T	W86R	0.991
19:48062019:G:C	F412L	0.989
19:48062019:G:T	F412L	0.989
19:48062021:A:G	F412L	0.989
19:48067807:G:C	N362K	0.989
19:48067807:G:T	N362K	0.989
19:48067822:C:A	W357C	0.989
19:48067822:C:G	W357C	0.989
19:48067821:C:A	G358W	0.988
19:48090404:A:C	S241R	0.988
19:48090404:A:T	S241R	0.988
19:48090406:T:G	S241R	0.988
19:48099778:A:G	W114R	0.988
19:48099778:A:T	W114R	0.988
19:48104672:G:T	A58D	0.987
19:48054897:G:C	F470L	0.986
19:48054897:G:T	F470L	0.986
19:48054899:A:G	F470L	0.986
19:48095588:G:C	F195L	0.986
19:48095588:G:T	F195L	0.986

dbSNP variants (sampled 300 via entrez): RS1000014696 (19:48103062 G>A), RS1000167431 (19:48109052 G>C), RS1000242388 (19:48068944 C>T), RS1000265144 (19:48054546 A>C), RS1000315187 (19:48069913 C>T), RS1000360176 (19:48080955 G>A,C), RS1000385662 (19:48098048 C>A,T), RS1000399919 (19:48057994 A>C,G), RS1000529057 (19:48067670 C>A,G,T), RS1000531910 (19:48068812 G>A), RS1000534996 (19:48108184 C>G), RS1000556160 (19:48063694 G>A,C), RS1000609 (19:48049172 C>T), RS1000622236 (19:48108008 CAATA>C), RS1000660447 (19:48074526 T>A)

Disease associations

OMIM: gene MIM:603602 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4834 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phospholipase A₂

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.38	IC50	4.2	nM	CHEMBL385730
6.78	IC50	165	nM	CHEMBL268905
6.38	IC50	420	nM	ARACHIDONYL TRIFLUOROMETHYLKETONE

PubChem BioAssay actives

3 with measured affinity, of 9 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[[(2S,4R)-1-[2-(2,4-difluorobenzoyl)benzoyl]-4-(triphenyl-lambda4-sulfanyl)pyrrolidin-2-yl]methyl]-4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]benzamide	55271: Concentration required to inhibit human Cytosolic phospholipase A2	ic50	0.0042	uM
N-[[(2S,4R)-1-(2-benzoylbenzoyl)-4-[(2-phenylphenyl)methoxy]pyrrolidin-2-yl]methyl]-4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]benzamide	55271: Concentration required to inhibit human Cytosolic phospholipase A2	ic50	0.1650	uM
(6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-one	55271: Concentration required to inhibit human Cytosolic phospholipase A2	ic50	0.4200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	increases expression, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
potassium perchlorate	decreases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
cannabidiol hydroxyquinone	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
3,4,5,4’-tetramethoxystilbene	affects expression	1
abrine	increases expression	1
SRM 1597	affects reaction, increases secretion, increases activity	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Troglitazone	increases expression	1
Glyphosate	increases expression	1
Arsenic	affects methylation	1
Atenolol	affects metabolic processing, affects response to substance	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4626966	Binding	Inhibition of human PLA2G4C expressed in HEK293T cell lysates at 10 uM preincubated for 30 mins followed by FP-TAMRA addition and measured after 20 mins by SDS-PAGE based competitive ABPP analysis	Structure-Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7XS	Ubigene A-549 PLA2G4C KO	Cancer cell line	Male

Clinical trials (associated diseases)

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