PLA2G2C

Summary

PLA2G2C (phospholipase A2 group IIC, HGNC:9032) is a protein-coding gene on chromosome 1p36.12, encoding Putative inactive group IIC secretory phospholipase A2 (Q5R387). Inactive phospholipase.

Predicted to enable several functions, including calcium ion binding activity; calcium-dependent phospholipase A2 activity; and phospholipid binding activity. Predicted to be involved in phosphatidylcholine metabolic process and phosphatidylglycerol metabolic process. Predicted to be located in extracellular region.

Source: NCBI Gene 391013 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 26 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001367969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9032
Approved symbol	PLA2G2C
Name	phospholipase A2 group IIC
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187980
Ensembl biotype	protein_coding
Entrez	391013

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000247992, ENST00000429261, ENST00000442226, ENST00000495760, ENST00000679259

RefSeq mRNA: 2 — MANE Select: NM_001367969 NM_001316722, NM_001367969

CCDS: CCDS90872

Canonical transcript exons

ENST00000679259 — 5 exons

Exon	Start	End
ENSE00001654041	20175007	20175145
ENSE00002178945	20172794	20172897
ENSE00003904835	20177324	20177439
ENSE00003905570	20186360	20186518
ENSE00003905775	20163055	20164157

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 93.55.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5684 / max 20.9531, expressed in 248 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10718	0.3358	167
10717	0.2327	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
muscle layer of sigmoid colon	UBERON:0035805	93.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.14	gold quality
lower esophagus	UBERON:0013473	87.11	gold quality
sperm	CL:0000019	86.94	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	84.63	gold quality
pancreatic ductal cell	CL:0002079	82.09	silver quality
lower esophagus mucosa	UBERON:0035834	81.34	gold quality
corpus epididymis	UBERON:0004359	80.57	gold quality
esophagus	UBERON:0001043	79.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.72	gold quality
mucosa of stomach	UBERON:0001199	76.67	gold quality
colon	UBERON:0001155	76.35	gold quality
large intestine	UBERON:0000059	76.00	gold quality
smooth muscle tissue	UBERON:0001135	76.00	gold quality
transverse colon	UBERON:0001157	75.09	gold quality
hypothalamus	UBERON:0001898	74.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.47	gold quality
seminal vesicle	UBERON:0000998	74.17	gold quality
prostate gland	UBERON:0002367	74.13	gold quality
right testis	UBERON:0004534	73.89	gold quality
left testis	UBERON:0004533	73.81	gold quality
intestine	UBERON:0000160	73.68	gold quality
medial globus pallidus	UBERON:0002477	73.37	silver quality
endothelial cell	CL:0000115	73.34	silver quality
caput epididymis	UBERON:0004358	73.34	gold quality
esophagus mucosa	UBERON:0002469	73.31	gold quality
testis	UBERON:0000473	72.97	gold quality
substantia nigra	UBERON:0002038	72.51	gold quality
cauda epididymis	UBERON:0004360	72.46	silver quality
anterior cingulate cortex	UBERON:0009835	71.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.61

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• LncRNA ubiquitin-binding protein domain protein 10 antisense RNA 1 inhibits colon adenocarcinoma progression via the miR-515-5p/slit guidance ligand 3 axis. (PMID:35034539)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pla2g2c	ENSMUSG00000028750
rattus_norvegicus	Pla2g2c	ENSRNOG00000016647
caenorhabditis_elegans		WBGENE00007419
caenorhabditis_elegans		WBGENE00015406

Paralogs (8): PLA2G10 (ENSG00000069764), PLA2G2D (ENSG00000117215), PLA2G5 (ENSG00000127472), PLA2G2F (ENSG00000158786), PLA2G1B (ENSG00000170890), PLA2G2A (ENSG00000188257), PLA2G2E (ENSG00000188784), OC90 (ENSG00000253117)

Protein

Protein identifiers

Putative inactive group IIC secretory phospholipase A2 — Q5R387 (reviewed: Q5R387)

Alternative names: Phosphatidylcholine 2-acylhydrolase-like protein GIIC

All UniProt accessions (2): Q5R387, J3KMZ3

UniProt curated annotations — full annotation on UniProt →

Function. Inactive phospholipase.

Subcellular location. Secreted.

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

Similarity. Belongs to the phospholipase A2 family.

RefSeq proteins (2): NP_001303651, NP_001354898* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00068

UniProt features (10 total): disulfide bond 4, binding site 3, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5R387-F1	72.52	0.01

Functional residue map

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

Ligand- & substrate-binding residues (3): 45; 47; 49

Disulfide bonds (4): 44–142, 77–107, 95–112, 97–105

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SECRETION, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOBP_LIPID_CATABOLIC_PROCESS, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (6): lipid catabolic process (GO:0016042), phosphatidylcholine metabolic process (GO:0046470), phosphatidylglycerol metabolic process (GO:0046471), arachidonate secretion (GO:0050482), lipid metabolic process (GO:0006629), phospholipid metabolic process (GO:0006644)

GO Molecular Function (7): signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), obsolete calcium-dependent phospholipase A2 activity (GO:0047498), A2-type glycerophospholipase activity (GO:0004623), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
glycerophospholipid metabolic process	2
catabolic process	1
icosanoid secretion	1
arachidonate transport	1
primary metabolic process	1
organophosphate metabolic process	1
protein binding	1
metal ion binding	1
lipid binding	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G2C	PLA2G12B	Q9BX93	743
PLA2G2C	PLA2G12A	Q9BZM1	616
PLA2G2C	PLA2G3	Q9NZ20	553
PLA2G2C	PLA2G4A	P47712	468
PLA2G2C	CYP2E1	P05181	464
PLA2G2C	PLA2G6	O60733	460
PLA2G2C	ENPP2	Q13822	459
PLA2G2C	PLA2G4C	Q9UP65	377
PLA2G2C	PLA2G4E	Q3MJ16	366
PLA2G2C	PLB1	Q6P1J6	358
PLA2G2C	APOB	P04114	353
PLA2G2C	PLA2G4D	Q86XP0	352
PLA2G2C	GOLGA8Q	H3BV12	349
PLA2G2C	ARL2BP	Q9Y2Y0	333
PLA2G2C	PLA2G4B	P0C869	305
PLA2G2C	TAS1R1	Q7RTX1	305

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A7E2Z9, A8MWY0, F8QN51, F8QN53, O15496, O54890, P00592, P00593, P00594, P04054, P04055, P04056, P04416, P06596, P14419, P14423, P14555, P20255, P20256, P24293, P39878, P43434, P48076, P81236, P81237, P86974, Q13822, Q1ZY03, Q2YHJ2, Q3UZV7, Q5R387, Q6EER3, Q6EER4, Q6EER6, Q71QE8, Q7M334, Q805A2, Q8JFB2, Q8JFG2, Q8R2H2

Diamond homologs: A0A411EZW9, A8CG78, A8CG84, A8CG87, A8CG90, A8E2V8, B5U6Z2, B6CQR5, C0HJC1, C0HKC3, C0HKC4, C0HLF0, C0HLL2, C0HMB2, C3W4R6, C9DPL5, D6MKR0, F8QN50, F8QN51, F8QN52, F8QN53, F8QN54, G3DT18, O42187, O42188, O42189, O42190, O42192, P00624, P04417, P06859, P06860, P0CAR9, P0DJN7, P0DKU1, P0DPS4, P14418, P14420, P18998, P20249

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

402 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20174990:AGAG:A	donor_gain	1.0000
1:20175002:CCCA:C	donor_loss	0.9900
1:20175003:CCA:C	donor_loss	0.9900
1:20175004:CACC:C	donor_loss	0.9900
1:20186149:GC:G	donor_gain	0.9900
1:20186150:C:G	donor_gain	0.9900
1:20186150:CTAG:C	donor_loss	0.9900
1:20186151:TAGGT:T	donor_loss	0.9900
1:20186152:AGG:A	donor_loss	0.9900
1:20186154:GTGAG:G	donor_loss	0.9900
1:20186155:T:A	donor_loss	0.9900
1:20186154:G:GG	donor_gain	0.9600
1:20186149:GCTAG:G	donor_gain	0.9500
1:20186379:C:G	donor_gain	0.9300
1:20172868:TC:T	acceptor_gain	0.9200
1:20186335:C:T	donor_gain	0.9200
1:20186479:G:GT	donor_gain	0.9200
1:20175003:CCACC:C	donor_gain	0.9100
1:20164156:ACCTA:A	acceptor_loss	0.9000
1:20164157:CCTAC:C	acceptor_loss	0.9000
1:20164158:CT:C	acceptor_loss	0.9000
1:20164159:T:A	acceptor_loss	0.9000
1:20173564:A:AC	donor_gain	0.9000
1:20173565:C:CC	donor_gain	0.9000
1:20175005:A:AC	donor_gain	0.9000
1:20175006:C:CC	donor_gain	0.9000
1:20175006:CCTGT:C	donor_gain	0.9000
1:20186303:C:T	donor_gain	0.8900
1:20172971:TCTAG:T	acceptor_gain	0.8800
1:20173555:TGAG:T	donor_gain	0.8800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000030539 (1:20179180 T>C), RS1000058678 (1:20182799 A>G), RS1000099080 (1:20172635 T>G), RS1000146214 (1:20179308 G>A,T), RS1000282639 (1:20173048 C>T), RS1000453322 (1:20171810 G>GGA), RS1000584984 (1:20172125 T>C), RS1000644567 (1:20184118 G>A), RS1000682419 (1:20177933 T>C), RS1000931781 (1:20183667 G>C), RS1001018321 (1:20167404 C>T), RS1001336540 (1:20173825 G>A,C), RS1001390203 (1:20173413 A>C), RS1001477802 (1:20165760 ATGTG>A,ATG), RS1001552106 (1:20179392 T>A,C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2097 (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)

ChEMBL bioactivities

11 potent at pChembl≥5 of 17 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.25	IC50	56	nM	CHEMBL4593409
6.94	IC50	114	nM	VARESPLADIB
6.88	IC50	131	nM	VARESPLADIB
6.40	IC50	400	nM	CHEMBL33789
6.24	IC50	570	nM	CHEMBL289247
6.00	IC50	1000	nM	CHEMBL1159973
6.00	IC50	1000	nM	CHEMBL1159974
5.18	IC50	6600	nM	CHEMBL418592
5.10	IC50	8000	nM	CHEMBL33036
5.05	IC50	8900	nM	CHEMBL30265
5.05	IC50	9000	nM	CHEMBL33056

PubChem BioAssay actives

4 with measured affinity, of 27 total; 2 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
(2R)-3-[3-(5-benzyl-2-carbamoylphenyl)phenyl]-2-methylpropanoic acid	1631141: Inhibition of sPLA2 in human HepG2 cells	ic50	0.0140	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxyacetic acid	1614038: Inhibition of human recombinant sPLA2 assessed as reduction in 16:0 LPC formation after 30 mins by HPLC-MS analysis	ic50	0.1140	uM

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Propofol	increases 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
CHEMBL802915	Binding	Compound was tested for the Inhibition of human Secretory phospholipase A 2 acyl hydrolysis using a membrane assay; Inactive	Tetrazole is an effective Sn-3 phosphate replacement in substrate analog inhibitors of 14 kDa phospholipase A2 — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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