PLA2R1

Summary

PLA2R1 (phospholipase A2 receptor 1, HGNC:9042) is a protein-coding gene on chromosome 2q24.2, encoding Secretory phospholipase A2 receptor (Q13018). Receptor for secretory phospholipase A2 (sPLA2).

This gene represents a phospholipase A2 receptor. The encoded protein likely exists as both a transmembrane form and a soluble form. The transmembrane receptor may play a role in clearance of phospholipase A2, thereby inhibiting its action. Polymorphisms at this locus have been associated with susceptibility to idiopathic membranous nephropathy. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 22925 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 224 total
• Druggable target: yes
• MANE Select transcript: NM_007366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9042
Approved symbol	PLA2R1
Name	phospholipase A2 receptor 1
Location	2q24.2
Locus type	gene with protein product
Status	Approved
Aliases	PLA2G1R, PLA2IR, PLA2-R, CLEC13C
Ensembl gene	ENSG00000153246
Ensembl biotype	protein_coding
OMIM	604939
Entrez	22925

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000283243, ENST00000392771, ENST00000460710, ENST00000890090, ENST00000890091, ENST00000890092, ENST00000890093, ENST00000890094, ENST00000966629

RefSeq mRNA: 3 — MANE Select: NM_007366 NM_001007267, NM_001195641, NM_007366

CCDS: CCDS33309, CCDS42767

Canonical transcript exons

ENST00000283243 — 30 exons

Exon	Start	End
ENSE00001009696	160022665	160022859
ENSE00001009698	159956510	159956627
ENSE00001009699	160042025	160042198
ENSE00001009701	160028850	160028963
ENSE00001009702	159951340	159951578
ENSE00001009705	159946801	159946917
ENSE00001009706	159983928	159984073
ENSE00001009707	160005652	160005821
ENSE00001009708	159955199	159955346
ENSE00001009709	159987156	159987358
ENSE00001009710	159977284	159977416
ENSE00001009711	160020106	160020263
ENSE00001009712	160028218	160028361
ENSE00001009713	159947419	159947559
ENSE00001009714	159955698	159955828
ENSE00001009715	160013263	160013375
ENSE00001009716	159944906	159945082
ENSE00001009717	159979830	159979914
ENSE00001009718	160044774	160045157
ENSE00001009719	159969256	159969359
ENSE00001009722	160016614	160016712
ENSE00001009725	159949608	159949776
ENSE00001009727	159976685	159976720
ENSE00001009728	159970148	159970212
ENSE00001009729	159976068	159976225
ENSE00001009730	159967539	159967678
ENSE00001317214	160032959	160033132
ENSE00001879049	159932006	159941992
ENSE00003680886	159942127	159942159
ENSE00003850718	160062295	160062615

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 93.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2562 / max 102.9514, expressed in 992 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31463	2.5741	915
31461	0.4533	287
31462	0.2030	72
31464	0.0257	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	93.97	gold quality
left lobe of thyroid gland	UBERON:0001120	92.70	gold quality
thyroid gland	UBERON:0002046	92.64	gold quality
calcaneal tendon	UBERON:0003701	91.91	gold quality
right lobe of thyroid gland	UBERON:0001119	91.69	gold quality
right coronary artery	UBERON:0001625	87.20	gold quality
saliva-secreting gland	UBERON:0001044	86.89	gold quality
tendon	UBERON:0000043	86.10	gold quality
popliteal artery	UBERON:0002250	86.06	gold quality
tibial artery	UBERON:0007610	86.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.49	gold quality
descending thoracic aorta	UBERON:0002345	85.35	gold quality
aorta	UBERON:0000947	85.34	gold quality
skin of leg	UBERON:0001511	85.31	gold quality
minor salivary gland	UBERON:0001830	85.28	gold quality
left ovary	UBERON:0002119	85.05	gold quality
skin of abdomen	UBERON:0001416	84.88	gold quality
body of uterus	UBERON:0009853	84.59	gold quality
ascending aorta	UBERON:0001496	84.55	gold quality
thoracic aorta	UBERON:0001515	84.55	gold quality
tendon of biceps brachii	UBERON:0008188	84.07	gold quality
left coronary artery	UBERON:0001626	83.96	gold quality
right ovary	UBERON:0002118	83.65	gold quality
zone of skin	UBERON:0000014	83.59	gold quality
gall bladder	UBERON:0002110	83.52	gold quality
mouth mucosa	UBERON:0003729	83.52	gold quality
coronary artery	UBERON:0001621	83.39	gold quality
adult mammalian kidney	UBERON:0000082	82.46	gold quality
ovary	UBERON:0000992	81.35	gold quality
stromal cell of endometrium	CL:0002255	80.66	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	6752.36
E-CURD-119	yes	5684.54
E-CURD-135	yes	4208.44
E-HCAD-10	yes	18.09
E-ANND-3	yes	9.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting PLA2R1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-29B-1-5P	98.86	68.35	1364

Literature-anchored findings (GeneRIF, showing 40)

• Results identify PLA2R (phospholipase A2 receptor) as a potential new tumour suppressor gene crucial in the induction of cellular senescence through the activation of the p53 pathway. (PMID:19197340)
• A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA(2)R indicating that it is a major antigen in this disease. (PMID:19571279)
• Single nucleotide polymorphisms in subjects’ PLA2R gene are associated with the risk of developing idiopathic membranous nephropathy. (PMID:20805699)
• Results provide evidence that genetic polymorphisms of phospholipase A2 receptor 1 may be the underlying cause of idiopathic membranous nephropathy. (PMID:20937089)
• An HLA-DQA1 allele on chromosome 6p21 is most closely associated with idiopathic membranous nephropathy in persons of white ancestry. This allele may facilitate an autoimmune response against targets such as variants of PLA2R1. (PMID:21323541)
• This research led to the identification of neutral endopeptidase, the M-type receptor for secretory phospholipase A(2) (PLA(2)R1) and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in membranous nephropathy. (PMID:22371247)
• Increased staining for PLA2R in glomeruli of renal biopsies tightly correlates with the presence of PLA2R autoantibodies in the serum and this may help discriminate between primary and secondary membranous nephropathy. (PMID:22673885)
• Data show that the genotyping technique of single nucleotide polymorphisms (SNPs) rs2187668 and rs4664308 within HLA-DQA1 and PLA2R1 is valuable for assessing susceptibility to idiopathic membranous nephropathy (IMN). (PMID:23194743)
• We present the largest case series to date examining PLA2R1 involvement in membranous glomerulopathy (PMID:23196797)
• High levels of PLA2R antibodies are linked with active disease and a higher risk of declining renal function during follow-up in idiopathic membranous nephropathy. (PMID:23364522)
• rare variants in the coding sequence of PLA2R1, including splice sites, are unlikely to explain the pathogenesis of idiopathic membranous nephropathy. (PMID:23431073)
• the interaction between PLA2R1 and HLA-DQA1 risk alleles associates with the development of idiopathic membranous nephropathy in the Chinese population. (PMID:23813219)
• PLA2R staining sensitivity is much lower in the pediatric than the adult primary membranous glomerulopathy population, suggesting a more diverse and currently incompletely described set of etiologies for this disease in this group. (PMID:23903693)
• An important role of PLA2R1 in controlling cancer cell death by influencing mitochondrial biology. (PMID:23994771)
• Suggest HLA-DQA1 and PLA2R1 polymorphisms can predict idiopathic membranous nephropathy response to immunosuppressors and disease progression. (PMID:24262501)
• The CC genotype and C allele at rs35771982 in PLA2R gene are associated with susceptibility to IMN in Chinese Hans. (PMID:24327152)
• We conclude that a decrease in PLA2R antibody level is associated with a decrease of proteinuria in patients with primary membranous nephropathy. (PMID:24610926)
• Data show loss of VHL, stabilization of HIF-2alpha and increased c-MYC activity, binding and transcriptional repression, through induction of PLA2R1 DNA methylation closed to PLA2R1 transcriptional start site, results in decreased PLA2R1 transcription. (PMID:24657971)
• This review compiles recent data demonstrating an unexpected tumor suppressive role of PLA2R1 and outlines the future work needed to improve our knowledge of the functions of this gene in cancer.[review] (PMID:24667060)
• anti-PLA2R in serum of patients with idiopathic membranous nephropathy was confirmed as a reliable diagnostic marker. (PMID:24779214)
• PLA2R1 plays a role in cancer as a tumor gene suppressor and is the major target antigen of auto-immune antibodies involved in idiopathic membranous nephropathy, a severe human kidney disease.[review] (PMID:24939538)
• Data show there was strong epistasis between HLA-DQA1 single nucleotide polymorphism rs2187668 and the phospholipase A2 receptor 1 (PLA2R1) variant rs35771982. (PMID:25187357)
• Studies indicate that phospholipase A2 receptor 1 (PLA2R1) may act as a clearance or signaling receptor for secreted phospholipase A2 (sPLA2s). (PMID:25230085)
• The sPLA2 IB-PLA2R interaction stimulated podocyte apoptosis through activating ERK1/2 and cPLA2alpha and through increasing the podocyte AA content (PMID:25335547)
• 15 of 154 patients with idiopathic membranous nephropathy had circulating autoantibodies to THSD7A but not to PLA2R1, a finding that suggests a distinct subgroup of patients with this condition. (PMID:25394321)
• Anti-PLA2R antibodies were found in Japanese patients with idiopathic membranous nephropathy; however, the prevalence was lower than that of any other Asian country. (PMID:25412738)
• Assessments of both serum PLA2R antibodies and PLA2R antigen in glomeruli were more sensitive for the diagnosis of PLA2R-related membranous nephropathy (PMID:25492250)
• Demonstrate pretransplantation circulating anti-PLA2R antibodies in a cohort of renal transplant recipients who prospectively developed recurrent disease. (PMID:25675198)
• Study showed that CTLD1-2 as well as the FNII domain of PLA2R were responsible for binding to collagen I and collagen-dependent migration in both mouse and human PLA2R. (PMID:25724334)
• serological anti-PLA2R testing has diagnostic value for differentiating iMN from sMN, but it must be interpreted in context with patient clinical characteristics (degree of proteinuria, immunosuppressive treatment, time of detection). (PMID:25740009)
• The detection and measurement of PLA2R-AB in idiopathic membranous nephropathy patients may be important tool in monitoring of the disease and efficacy of the treatment. (PMID:25953939)
• Case Report: PLA2R positive membranous nephropathy in kidney transplant recipient with both IgA nephropathy and HCV infection long after kidney transplant from identical twin. (PMID:26031599)
• Renal biopsy PLA2R positivity was common in idiopathic membranous nephropathy (MN) and HBV-MN but rare in lupus-associated MN, and it was closely associated with serum PLA2R-Ab production. (PMID:26087695)
• Suggest that PLA2R has a contributory role in the pathogenesis of paediatric idiopathic membranous nephropathy. (PMID:26194981)
• Report both serum and kidney levels of PLA2R1 autoantibody in idiopathic membranous nephropathy. (PMID:26369693)
• Data indicate that enhanced granular expression of phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) was detected in 9.1% and 52.7%, respectively, of the patients with idiopathic membranous nephropathy (MN). (PMID:26393352)
• Accordingly, PLA2R ABs assay seems to be promising tool not only to diagnose MN but also to predict the course of the disease and could open the way to personalize therapy. [review] (PMID:26576418)
• genetic polymorphism is associated with systemic lupus erythematosus and lupus nephritis in a Chinese patients (PMID:26645973)
• PLA2R1 expression in breast cancer cells is controlled by DNA methylation and histone modifications (PMID:26672991)
• Single-nucleotide polymorphism in PLA2R1 gene is associated with primary membranous nephropathy. (PMID:26673907)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pla2r1	ENSDARG00000077474
mus_musculus	Pla2r1	ENSMUSG00000054580
rattus_norvegicus	Pla2r1	ENSRNOG00000008129

Paralogs (4): MRC2 (ENSG00000011028), LY75 (ENSG00000054219), CD302 (ENSG00000241399), MRC1 (ENSG00000260314)

Protein

Protein identifiers

Secretory phospholipase A2 receptor — Q13018 (reviewed: Q13018)

Alternative names: 180 kDa secretory phospholipase A2 receptor, C-type lectin domain family 13 member C, M-type receptor

All UniProt accessions (2): Q13018, B7ZML4

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for secretory phospholipase A2 (sPLA2). Acts as a receptor for phospholipase sPLA2-IB/PLA2G1B but not sPLA2-IIA/PLA2G2A. Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow-derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in pro-inflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B. In podocytes, binding of sPLA2-IB/PLA2G1B can regulate podocyte survival and glomerular homeostasis.

Subunit / interactions. Interacts with sPLA2-IB/PLA2G1B; this interaction mediates intracellular signaling as well as clearance of extracellular sPLA2-IB/PLA2G1B via endocytotic pathway. Interacts with sPLA2-X/PLA2G10; this interaction mediates sPLA2-X/PLA2G10 clearance and inactivation.

Subcellular location. Cell membrane Secreted Secreted.

Tissue specificity. Expressed in podocytes (at protein level). Present in lung macrophage (at protein level). Highly expressed in kidney. Also expressed in pancreas, amnion, choriodecidua and placenta. Isoform 2 is expressed at much lower level.

Post-translational modifications. The secretory phospholipase A2 receptor form may be produced by the action of metalloproteinases. It contains all extracellular domains and only lacks transmembrane and cytosolic regions. It is however unclear whether this form is produced by proteolytic cleavage as suggested by some experiments, or by alternative splicing, as in the case of isoform 2 that shares all characteristics of secretory phospholipase A2 receptor form.

Domain organisation. C-type lectin domains 3-5 mediate the interaction with phospholipase PLA2G1B. The endocytosis signal probably mediates endocytosis via clathrin-coated pits.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13018-1	1	yes
Q13018-2	2

RefSeq proteins (3): NP_001007268, NP_001182570, NP_031392* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000562	FN_type2_dom	Domain
IPR000772	Ricin_B_lectin	Domain
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR035992	Ricin_B-like_lectins	Homologous_superfamily
IPR036943	FN_type2_sf	Homologous_superfamily
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00040, PF00059, PF24562

UniProt features (64 total): disulfide bond 17, domain 10, sequence variant 8, sequence conflict 7, strand 7, glycosylation site 3, helix 3, chain 2, topological domain 2, splice variant 2, signal peptide 1, short sequence motif 1, transmembrane region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6JLI	X-RAY DIFFRACTION	1.78
7QSR	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13018-F1	79.16	0.29

Functional residue map

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

Disulfide bonds (17): 51–64, 89–106, 178–204, 192–219, 260–354, 330–346, 406–501, 478–493, 617–634, 699–796, 774–788, 840–937, 914–929, 1067–1087, 1209–1223, 1280–1377, 1354–1369

Glycosylation sites (3): 93, 454, 1123

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: 195 (showing top): GOBP_POSITIVE_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_ICOSANOID_SECRETION, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELLULAR_SENESCENCE, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, MORF_RAD51L3, GOBP_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR

GO Biological Process (10): positive regulation of cytokine production (GO:0001819), receptor-mediated endocytosis (GO:0006898), positive regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043517), reactive oxygen species metabolic process (GO:0072593), positive regulation of arachidonate secretion (GO:0090238), replicative senescence (GO:0090399), oxidative stress-induced premature senescence (GO:0090403), negative regulation of arachidonate secretion (GO:1900139), positive regulation of podocyte apoptotic process (GO:1904635), endocytosis (GO:0006897)

GO Molecular Function (4): phospholipase A2 inhibitor activity (GO:0019834), carbohydrate binding (GO:0030246), signaling receptor activity (GO:0038023), phospholipase binding (GO:0043274)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), cell surface (GO:0009986), signaling receptor complex (GO:0043235), membrane (GO:0016020)

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
cellular anatomical structure	3
arachidonate secretion	2
regulation of arachidonate secretion	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
endocytosis	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
positive regulation of signal transduction by p53 class mediator	1
metabolic process	1
positive regulation of icosanoid secretion	1
cell cycle process	1
cellular response to oxidative stress	1
stress-induced premature senescence	1
negative regulation of icosanoid secretion	1
podocyte apoptotic process	1
positive regulation of epithelial cell apoptotic process	1
regulation of podocyte apoptotic process	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
A2-type glycerophospholipase activity	1
phospholipase inhibitor activity	1
binding	1
molecular transducer activity	1
enzyme binding	1
membrane	1
cell periphery	1
protein-containing complex	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2R1	PLA2G2A	P14555	930
PLA2R1	PLA2G10	O15496	926
PLA2R1	THSD7A	Q9UPZ6	912
PLA2R1	PLA2G2D	Q9UNK4	911
PLA2R1	PLA2G1B	P04054	884
PLA2R1	Q5Y7H0	Q5Y7H0	775
PLA2R1	NELL1	Q92832	718
PLA2R1	SEMA3B	Q13214	671
PLA2R1	AKR1B1	P15121	667
PLA2R1	ALB	P02768	633
PLA2R1	HLA-DQA2	P01906	621
PLA2R1	PLA2G2E	Q9NZK7	603
PLA2R1	EXT1	Q16394	582
PLA2R1	EXT2	Q93063	580
PLA2R1	APOL1	O14791	511
PLA2R1	LRP2	P98164	511

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PLA2R1	ACTC1	psi-mi:“MI:0915”(physical association)	0.400
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): PLA2R1 (Proximity Label-MS), PLA2R1 (Affinity Capture-MS), PLA2R1 (Proximity Label-MS)

ESM2 similar proteins: A3FM55, B4XSY7, B4XSY8, B4XSZ1, C0HKZ6, D1MGU0, F1QVU0, O09037, O60449, O75596, O89103, O93426, P06681, P14371, P18292, P19221, P21180, P23132, P25031, P28824, P30836, P35230, P35231, P49259, P49260, P81017, P81112, P98131, Q08731, Q09GJ8, Q09GK0, Q13018, Q28008, Q3SYW2, Q4PRD2, Q568T5, Q5R880, Q60767, Q62028, Q6T7B5

Diamond homologs: A7X3W1, A7X3W6, A7X3Z4, A7X3Z7, B0VXV2, B4XSY4, B4XSY5, B4XSY6, B4XSY9, B4XSZ0, B4XSZ2, B4XSZ4, B4XSZ5, B4XSZ7, B4XSZ8, B4XSZ9, D2YVK5, D2YW39, J3SBP0, O09037, O09049, O60449, P05451, P0DJL4, P10758, P23132, P25031, P35230, P35231, P42854, P43137, P48304, P49259, P81111, P81112, P81115, Q06141, Q08731, Q13018, Q29191

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	174
Likely benign	21
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

5617 predictions. Top by Δscore:

Variant	Effect	Δscore
2:159942123:GTACC:G	donor_loss	1.0000
2:159942124:TAC:T	donor_loss	1.0000
2:159942125:A:AG	donor_loss	1.0000
2:159942160:C:CC	acceptor_gain	1.0000
2:159946799:A:AC	donor_gain	1.0000
2:159946800:C:CC	donor_gain	1.0000
2:159947887:C:CA	donor_gain	1.0000
2:159949724:C:CT	acceptor_gain	1.0000
2:159949725:A:T	acceptor_gain	1.0000
2:159955262:C:CT	acceptor_gain	1.0000
2:159955263:A:T	acceptor_gain	1.0000
2:159955264:G:GC	acceptor_gain	1.0000
2:159955696:A:AC	donor_gain	1.0000
2:159955697:C:CC	donor_gain	1.0000
2:159956626:CA:C	acceptor_gain	1.0000
2:159969314:T:TA	donor_gain	1.0000
2:159970142:TCATA:T	donor_loss	1.0000
2:159970143:CATA:C	donor_loss	1.0000
2:159970144:AT:A	donor_loss	1.0000
2:159970145:TA:T	donor_loss	1.0000
2:159970146:A:AC	donor_gain	1.0000
2:159970147:C:CC	donor_gain	1.0000
2:159970210:TAG:T	acceptor_gain	1.0000
2:159970211:AGCTA:A	acceptor_loss	1.0000
2:159970212:GC:G	acceptor_loss	1.0000
2:159970213:C:CC	acceptor_gain	1.0000
2:159970213:C:CG	acceptor_loss	1.0000
2:159970214:T:C	acceptor_loss	1.0000
2:159970216:T:C	acceptor_gain	1.0000
2:159970216:T:TC	acceptor_gain	1.0000

AlphaMissense

9782 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:159987306:C:A	W629C	0.997
2:159987306:C:G	W629C	0.997
2:159977305:A:G	W794R	0.996
2:159977305:A:T	W794R	0.996
2:159979845:C:A	W751C	0.996
2:159979845:C:G	W751C	0.996
2:159949663:C:A	W1218C	0.995
2:159949663:C:G	W1218C	0.995
2:159977303:C:A	W794C	0.995
2:159977303:C:G	W794C	0.995
2:159979847:A:G	W751R	0.995
2:159979847:A:T	W751R	0.995
2:159984015:C:T	C699Y	0.995
2:160044922:C:A	W115C	0.995
2:160044922:C:G	W115C	0.995
2:159949665:A:G	W1218R	0.994
2:159949665:A:T	W1218R	0.994
2:159951361:C:A	W1173C	0.994
2:159951361:C:G	W1173C	0.994
2:159951454:G:C	C1142W	0.994
2:159967671:C:A	W924C	0.994
2:159967671:C:G	W924C	0.994
2:159977298:C:G	C796S	0.994
2:159977299:A:T	C796S	0.994
2:159984035:C:A	W692C	0.994
2:159984035:C:G	W692C	0.994
2:159987189:C:A	W668C	0.994
2:159987189:C:G	W668C	0.994
2:160005668:C:A	W606C	0.994
2:160005668:C:G	W606C	0.994

dbSNP variants (sampled 300 via entrez): RS1000047314 (2:160056126 G>C,T), RS1000057414 (2:160019053 G>A), RS1000112541 (2:160008179 G>A,T), RS1000117161 (2:159925992 G>A,T), RS1000177164 (2:160049363 T>C), RS1000184543 (2:160044731 A>C,G,T), RS1000207411 (2:160020386 G>A), RS1000231336 (2:160049131 G>A), RS1000240282 (2:159935819 C>T), RS1000249777 (2:159965833 G>A), RS1000250467 (2:159956958 T>C), RS1000265710 (2:159964123 A>G), RS1000292050 (2:160010919 T>G), RS1000317917 (2:160053349 G>A,C,T), RS1000329185 (2:160053045 AAT>A)

Disease associations

OMIM: gene MIM:604939 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): kidney disorder (MONDO:0005240), atypical hemolytic-uremic syndrome (MONDO:0016244)

Orphanet (1): Atypical hemolytic uremic syndrome (Orphanet:2134)

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000730_11	Bilirubin levels	2.000000e-13
GCST000984_1	Idiopathic membranous nephropathy	9.000000e-29
GCST003043_85	Inflammatory bowel disease	3.000000e-08
GCST003044_22	Crohn’s disease	1.000000e-06
GCST003402_1	Membranous nephropathy	4.000000e-10
GCST006585_1180	Blood protein levels	3.000000e-158
GCST007277_3	Tourette syndrome	2.000000e-07
GCST010002_402	Refractive error	8.000000e-10
GCST010004_1	Membranous nephropathy	5.000000e-103
GCST010005_1	Membranous nephropathy	5.000000e-48
GCST010006_1	Membranous nephropathy	4.000000e-61
GCST010916_9	Proportion of activated microglia (inferior temporal cortex)	2.000000e-06
GCST90002400_337	Plateletcrit	3.000000e-17
GCST90002402_254	Platelet count	1.000000e-09
GCST90020025_1536	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90020027_467	Waist-hip index	5.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713395 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.83	Kd	1470	nM	MACROCARPAL B

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 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
5-[(1S)-1-[(1aR,4R,4aR,7S,7aS,7bR)-4-hydroxy-1,1,4,7-tetramethyl-1a,2,3,4a,5,6,7a,7b-octahydrocyclopropa[h]azulen-7-yl]-3-methylbutyl]-2,4,6-trihydroxybenzene-1,3-dicarbaldehyde	2112807: Binding affinity to human recombinant PLA2 receptor assessed as dissociation constant by SPR analysis	kd	1.4700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Valproic Acid	increases expression	2
aristolochic acid I	decreases expression	1
trichostatin A	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	increases expression	1
Decitabine	increases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Hydrogen Peroxide	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vanadates	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Antirheumatic Agents	increases expression	1
tert-Butylhydroperoxide	increases expression	1
Vitamin K 3	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
CHEMBL3777203	Binding	Binding affinity to human sPLA2 at 10 uM	Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	PHASE4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes