PLA2G12B

Summary

PLA2G12B (phospholipase A2 group XIIB, HGNC:18555) is a protein-coding gene on chromosome 10q22.1, encoding Group XIIB secretory phospholipase A2-like protein (Q9BX93). Not known; does not seem to have catalytic activity.

The protein encoded by this gene belongs to the phospholipase A2 (PLA2) group of enzymes, which function in glycolipid hydrolysis with the release of free fatty acids and lysophospholipids. This family member has altered phospholipid-binding properties and is catalytically inactive. The protein is secreted, and together with microsomal triglyceride transfer protein, it functions to regulate HNF4alpha-induced hepatitis C virus infectivity. The expression of this gene is down-regulated in various tumors, suggesting that it may function as a negative regulator of tumor progression. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 84647 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 21 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_032562

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18555
Approved symbol	PLA2G12B
Name	phospholipase A2 group XIIB
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138308
Ensembl biotype	protein_coding
OMIM	611653
Entrez	84647

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000373032, ENST00000883773, ENST00000883774, ENST00000883775, ENST00000883776, ENST00000964945

RefSeq mRNA: 3 — MANE Select: NM_032562 NM_001318124, NM_001318125, NM_032562

CCDS: CCDS7319

Canonical transcript exons

ENST00000373032 — 4 exons

Exon	Start	End
ENSE00000933770	72941169	72941334
ENSE00000933771	72942652	72942740
ENSE00001459369	72934762	72935738
ENSE00001459374	72954475	72954806

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 91.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5352 / max 88.8655, expressed in 87 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110018	0.3251	69
110019	0.0906	35
110016	0.0815	42
110017	0.0380	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	91.78	gold quality
ileal mucosa	UBERON:0000331	91.57	gold quality
liver	UBERON:0002107	91.03	gold quality
right lobe of liver	UBERON:0001114	89.84	gold quality
duodenum	UBERON:0002114	88.27	gold quality
kidney epithelium	UBERON:0004819	84.52	silver quality
mucosa of transverse colon	UBERON:0004991	76.14	gold quality
small intestine	UBERON:0002108	74.86	gold quality
jejunum	UBERON:0002115	74.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.28	gold quality
adult mammalian kidney	UBERON:0000082	71.35	gold quality
cardiac muscle of right atrium	UBERON:0003379	67.95	gold quality
sperm	CL:0000019	67.82	silver quality
left ventricle myocardium	UBERON:0006566	67.16	gold quality
kidney	UBERON:0002113	66.75	gold quality
cardiac atrium	UBERON:0002081	66.35	gold quality
right atrium auricular region	UBERON:0006631	66.14	gold quality
myocardium	UBERON:0002349	65.80	gold quality
epithelial cell of pancreas	CL:0000083	64.68	gold quality
tibialis anterior	UBERON:0001385	64.65	silver quality
parotid gland	UBERON:0001831	64.13	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	63.95	gold quality
secondary oocyte	CL:0000655	63.64	silver quality
rectum	UBERON:0001052	63.49	gold quality
endothelial cell	CL:0000115	62.95	gold quality
deltoid	UBERON:0001476	62.60	gold quality
nasal cavity epithelium	UBERON:0005384	62.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	61.53	gold quality
heart right ventricle	UBERON:0002080	61.13	gold quality
pancreatic ductal cell	CL:0002079	60.78	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	10.42
E-ANND-3	yes	3.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

30 targeting PLA2G12B, 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-4673	100.00	66.64	1490
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-4327	97.21	67.71	676
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-668-3P	96.18	65.80	673
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-4330	95.44	66.39	993
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-7109-3P	94.23	67.19	743

Literature-anchored findings (GeneRIF, showing 1)

• FXR regulates serum triglyceride level in part through PLA2G12B. (PMID:27471003)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pla2g12b	ENSDARG00000015662
mus_musculus	Pla2g12b	ENSMUSG00000009646
rattus_norvegicus	Pla2g12b	ENSRNOG00000046619
drosophila_melanogaster	GXIVsPLA2	FBGN0036545
caenorhabditis_elegans		WBGENE00016288
caenorhabditis_elegans		WBGENE00018411

Paralogs (1): PLA2G12A (ENSG00000123739)

Protein

Protein identifiers

Group XIIB secretory phospholipase A2-like protein — Q9BX93 (reviewed: Q9BX93)

Alternative names: Group XIII secretory phospholipase A2-like protein, sPLA2-GXIIB

All UniProt accessions (1): Q9BX93

UniProt curated annotations — full annotation on UniProt →

Function. Not known; does not seem to have catalytic activity.

Subcellular location. Secreted.

Tissue specificity. Strong expression in liver, small intestine and kidney.

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

Similarity. Belongs to the phospholipase A2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BX93-1	1	yes
Q9BX93-2	2

RefSeq proteins (3): NP_001305053, NP_001305054, NP_115951* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010711	PLA2G12	Family
IPR036444	PLipase_A2_dom_sf	Homologous_superfamily

Pfam: PF06951

UniProt features (7 total): binding site 4, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BX93-F1	71.90	0.25

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 (4): 89; 91; 93; 116

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_STEROL_HOMEOSTASIS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY, GOBP_ORGANIC_ACID_TRANSPORT, COUP_01, GOBP_LIPID_HOMEOSTASIS, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SECRETION, GOBP_LIPID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, SABATES_COLORECTAL_ADENOMA_DN, GOBP_LIPID_CATABOLIC_PROCESS

GO Biological Process (5): phospholipid metabolic process (GO:0006644), lipid catabolic process (GO:0016042), cholesterol homeostasis (GO:0042632), arachidonate secretion (GO:0050482), triglyceride homeostasis (GO:0070328)

GO Molecular Function (3): A2-type glycerophospholipase activity (GO:0004623), calcium ion binding (GO:0005509), 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
organophosphate metabolic process	1
catabolic process	1
sterol homeostasis	1
icosanoid secretion	1
arachidonate transport	1
acylglycerol homeostasis	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
metal ion binding	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G12B	PLA2G10	O15496	917
PLA2G12B	PLA2G2A	P14555	793
PLA2G12B	PLA2G2C	Q5R387	743
PLA2G12B	PLA2G2F	Q9BZM2	631
PLA2G12B	PLA2G3	Q9NZ20	623
PLA2G12B	PLA2G2E	Q9NZK7	605
PLA2G12B	PLA2G1B	P04054	557
PLA2G12B	ANKS4B	Q8N8V4	539
PLA2G12B	PLA2G2D	Q9UNK4	532
PLA2G12B	PLA2G5	P39877	523
PLA2G12B	ENPP2	Q13822	483
PLA2G12B	N4BP2L1	Q5TBK1	472
PLA2G12B	PLA2G4C	Q9UP65	435
PLA2G12B	CYP2E1	P05181	421
PLA2G12B	OC90	Q02509	420

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PLA2G12B	CCPG1	psi-mi:“MI:0915”(physical association)	0.400
PLA2G12B	NOMO1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): ADAMTS1 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), GLG1 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), NOMO1 (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A0JPH4, A2A8U2, A2ATD1, A6QLD2, B1AKI9, B1AL88, B3KU38, O14525, O35757, O75129, P0DPB3, P0DPB4, P12755, P17863, P27424, P49140, P55001, P55002, P85299, P97953, Q3V1G4, Q58CS8, Q5EGE1, Q5QQ56, Q5QQ57, Q60698, Q61137, Q68BL8, Q6DVA0, Q6L8S8, Q6L9W6, Q6S5C2, Q6ZWB6, Q80U62, Q80Z10, Q812A5, Q86Y38, Q8CCS2, Q8JG33

Diamond homologs: Q99P27, Q9BX93, Q9BZM1, Q9EPR2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

556 predictions. Top by Δscore:

Variant	Effect	Δscore
10:72941333:AT:A	acceptor_gain	1.0000
10:72941345:G:C	acceptor_gain	1.0000
10:72941345:G:GC	acceptor_gain	1.0000
10:72942651:CA:C	donor_gain	1.0000
10:72942742:T:C	acceptor_gain	1.0000
10:72935734:GGCTG:G	acceptor_gain	0.9900
10:72935736:CTG:C	acceptor_gain	0.9900
10:72935740:T:C	acceptor_gain	0.9900
10:72935740:T:TC	acceptor_gain	0.9900
10:72941162:CACCT:C	donor_loss	0.9900
10:72941163:ACCTA:A	donor_loss	0.9900
10:72941164:CCTA:C	donor_loss	0.9900
10:72941165:CTA:C	donor_loss	0.9900
10:72941166:TA:T	donor_loss	0.9900
10:72941167:A:AG	donor_loss	0.9900
10:72941330:TCCAT:T	acceptor_gain	0.9900
10:72941331:CCAT:C	acceptor_gain	0.9900
10:72941331:CCATC:C	acceptor_gain	0.9900
10:72941332:CAT:C	acceptor_gain	0.9900
10:72941332:CATC:C	acceptor_gain	0.9900
10:72941335:C:CC	acceptor_gain	0.9900
10:72941335:C:CG	acceptor_loss	0.9900
10:72942650:A:AC	donor_gain	0.9900
10:72942651:C:CC	donor_gain	0.9900
10:72942742:T:TC	acceptor_gain	0.9900
10:72942746:A:T	acceptor_gain	0.9900
10:72954469:ACTC:A	donor_loss	0.9900
10:72954470:CTCA:C	donor_loss	0.9900
10:72954471:T:TC	donor_loss	0.9900
10:72954472:CACCA:C	donor_loss	0.9900

AlphaMissense

1277 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:72941249:C:G	C129S	0.998
10:72941250:A:T	C129S	0.998
10:72941257:T:A	K126N	0.998
10:72941257:T:G	K126N	0.998
10:72954495:C:G	C64S	0.998
10:72954496:A:T	C64S	0.998
10:72935662:C:A	Q181H	0.997
10:72935662:C:G	Q181H	0.997
10:72935674:A:C	F177L	0.997
10:72935674:A:T	F177L	0.997
10:72935675:A:C	F177C	0.997
10:72935676:A:G	F177L	0.997
10:72935684:C:G	C174S	0.997
10:72935685:A:T	C174S	0.997
10:72941249:C:A	C129F	0.997
10:72941249:C:T	C129Y	0.997
10:72941270:C:G	C122S	0.997
10:72941270:C:T	C122Y	0.997
10:72941271:A:T	C122S	0.997
10:72954483:C:G	C68S	0.997
10:72954484:A:T	C68S	0.997
10:72935650:G:C	C185W	0.996
10:72935651:C:T	C185Y	0.996
10:72941225:A:G	L137P	0.996
10:72941248:A:C	C129W	0.996
10:72941250:A:G	C129R	0.996
10:72941258:T:A	K126I	0.996
10:72941271:A:G	C122R	0.996
10:72941283:A:G	C118R	0.996
10:72941300:C:G	C112S	0.996

dbSNP variants (sampled 300 via entrez): RS1000379177 (10:72938138 A>G), RS1000381886 (10:72937839 G>A), RS1000490062 (10:72945413 T>C), RS1000580585 (10:72952478 C>G), RS1000841054 (10:72944957 C>T), RS1000861439 (10:72939615 A>G), RS1000894304 (10:72939827 T>C), RS1001194880 (10:72938228 A>G), RS1001363985 (10:72953324 T>C,G), RS1001473779 (10:72945779 C>T), RS1001536731 (10:72947810 G>C,T), RS1001591322 (10:72952652 T>C), RS1001622395 (10:72952942 T>G), RS1001666911 (10:72945829 G>C), RS1001901557 (10:72946216 CT>C)

Disease associations

OMIM: gene MIM:611653 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006613_30	Triglycerides	1.000000e-09
GCST006624_63	Systolic blood pressure	2.000000e-12
GCST010002_290	Refractive error	2.000000e-17
GCST010173_142	Triglyceride levels	6.000000e-09
GCST010242_104	HDL cholesterol levels	2.000000e-08
GCST010244_160	Triglyceride levels	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): 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

3 potent at pChembl≥5 of 4 total, top 3 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

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

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Cyclosporine	decreases expression	3
bisphenol A	affects expression, decreases methylation	2
Valproic Acid	affects expression, decreases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
vanadyl sulfate	increases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Rosiglitazone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Fonofos	increases methylation	1
Endosulfan	affects cotreatment, decreases expression	1
Folic Acid	increases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Zinc	affects cotreatment, increases expression	1
Aflatoxin B1	affects expression	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4383327	Binding	Inhibition of human sPLA2	1-(2-Hydroxybenzoyl)-thiosemicarbazides are promising antimicrobial agents targeting d-alanine-d-alanine ligase in bacterio. — Eur J Med Chem

Clinical trials (associated diseases)

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