PLA2G4A (phospholipase A2 group IVA)

Gene

• Entrez ID: 5321
• Gene name: Phospholipase A2 group IVA
• Gene symbol: PLA2G4A
• Synonyms (NCBI Gene): GURDP, PLA2G4, cPLA2, cPLA2-alpha
• Chromosome: 1
• Chromosome location: 1q31.1
• Summary: This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandi

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121434634	T>C	Pathogenic	Missense variant, coding sequence variant
rs121434635	G>A	Pathogenic	Missense variant, coding sequence variant
rs1557895416	G>C	Pathogenic	Coding sequence variant, missense variant
rs1557901999	AGTA>-	Pathogenic	Intron variant, splice donor variant
rs1571392612	->T	Pathogenic	Coding sequence variant, frameshift variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022551	hsa-miR-124-3p	Microarray	18668037
MIRT028507	hsa-miR-30a-5p	Proteomics	18668040
MIRT047518	hsa-miR-10a-5p	CLASH	23622248
MIRT041616	hsa-miR-146b-5p	CLASH	23622248
MIRT052653	hsa-miR-449c-5p	CLASH	23622248
MIRT700778	hsa-miR-6808-5p	HITS-CLIP	23313552
MIRT700777	hsa-miR-6893-5p	HITS-CLIP	23313552
MIRT700776	hsa-miR-940	HITS-CLIP	23313552
MIRT700775	hsa-miR-3929	HITS-CLIP	23313552
MIRT700774	hsa-miR-4419b	HITS-CLIP	23313552
MIRT700773	hsa-miR-4478	HITS-CLIP	23313552
MIRT700772	hsa-miR-6783-5p	HITS-CLIP	23313552
MIRT700771	hsa-miR-5588-3p	HITS-CLIP	23313552
MIRT700770	hsa-miR-2114-5p	HITS-CLIP	23313552
MIRT700769	hsa-miR-5690	HITS-CLIP	23313552
MIRT700768	hsa-miR-6746-5p	HITS-CLIP	23313552
MIRT700767	hsa-miR-4649-3p	HITS-CLIP	23313552
MIRT700766	hsa-miR-1827	HITS-CLIP	23313552
MIRT700765	hsa-miR-485-5p	HITS-CLIP	23313552
MIRT700764	hsa-miR-6884-5p	HITS-CLIP	23313552
MIRT700763	hsa-miR-1909-3p	HITS-CLIP	23313552
MIRT700762	hsa-miR-6722-3p	HITS-CLIP	23313552
MIRT700761	hsa-miR-7160-5p	HITS-CLIP	23313552
MIRT700760	hsa-miR-1207-5p	HITS-CLIP	23313552
MIRT700759	hsa-miR-4763-3p	HITS-CLIP	23313552
MIRT700758	hsa-miR-6771-5p	HITS-CLIP	23313552
MIRT700757	hsa-miR-665	HITS-CLIP	23313552
MIRT671771	hsa-miR-1228-3p	HITS-CLIP	23824327
MIRT671770	hsa-miR-4691-3p	HITS-CLIP	23824327
MIRT671769	hsa-miR-342-3p	HITS-CLIP	23824327
MIRT671768	hsa-miR-4755-3p	HITS-CLIP	23824327
MIRT671767	hsa-miR-4284	HITS-CLIP	23824327
MIRT671766	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671765	hsa-miR-3157-5p	HITS-CLIP	23824327
MIRT671764	hsa-miR-7977	HITS-CLIP	23824327
MIRT700778	hsa-miR-6808-5p	HITS-CLIP	23313552
MIRT700777	hsa-miR-6893-5p	HITS-CLIP	23313552
MIRT700776	hsa-miR-940	HITS-CLIP	23313552
MIRT700775	hsa-miR-3929	HITS-CLIP	23313552
MIRT700774	hsa-miR-4419b	HITS-CLIP	23313552
MIRT700773	hsa-miR-4478	HITS-CLIP	23313552
MIRT700772	hsa-miR-6783-5p	HITS-CLIP	23313552
MIRT700771	hsa-miR-5588-3p	HITS-CLIP	23313552
MIRT700770	hsa-miR-2114-5p	HITS-CLIP	23313552
MIRT700769	hsa-miR-5690	HITS-CLIP	23313552
MIRT700768	hsa-miR-6746-5p	HITS-CLIP	23313552
MIRT700767	hsa-miR-4649-3p	HITS-CLIP	23313552
MIRT700766	hsa-miR-1827	HITS-CLIP	23313552
MIRT700765	hsa-miR-485-5p	HITS-CLIP	23313552
MIRT700764	hsa-miR-6884-5p	HITS-CLIP	23313552
MIRT700763	hsa-miR-1909-3p	HITS-CLIP	23313552
MIRT700762	hsa-miR-6722-3p	HITS-CLIP	23313552
MIRT700761	hsa-miR-7160-5p	HITS-CLIP	23313552
MIRT700760	hsa-miR-1207-5p	HITS-CLIP	23313552
MIRT700759	hsa-miR-4763-3p	HITS-CLIP	23313552
MIRT700758	hsa-miR-6771-5p	HITS-CLIP	23313552
MIRT700757	hsa-miR-665	HITS-CLIP	23313552
MIRT671771	hsa-miR-1228-3p	HITS-CLIP	23824327
MIRT671770	hsa-miR-4691-3p	HITS-CLIP	23824327
MIRT671769	hsa-miR-342-3p	HITS-CLIP	23824327
MIRT671768	hsa-miR-4755-3p	HITS-CLIP	23824327
MIRT671767	hsa-miR-4284	HITS-CLIP	23824327
MIRT671766	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT671765	hsa-miR-3157-5p	HITS-CLIP	23824327
MIRT671764	hsa-miR-7977	HITS-CLIP	23824327
MIRT2594860	hsa-miR-1183	CLIP-seq
MIRT2594861	hsa-miR-1301	CLIP-seq
MIRT2594862	hsa-miR-145	CLIP-seq
MIRT2594863	hsa-miR-3180-5p	CLIP-seq
MIRT2594864	hsa-miR-362-5p	CLIP-seq
MIRT2594865	hsa-miR-3647-3p	CLIP-seq
MIRT2594866	hsa-miR-369-3p	CLIP-seq
MIRT2594867	hsa-miR-374a	CLIP-seq
MIRT2594868	hsa-miR-374b	CLIP-seq
MIRT2594869	hsa-miR-383	CLIP-seq
MIRT2594870	hsa-miR-433	CLIP-seq
MIRT2594871	hsa-miR-4660	CLIP-seq
MIRT2594872	hsa-miR-4676-5p	CLIP-seq
MIRT2594873	hsa-miR-4712-5p	CLIP-seq
MIRT2594874	hsa-miR-4714-3p	CLIP-seq
MIRT2594875	hsa-miR-4769-3p	CLIP-seq
MIRT2594876	hsa-miR-4772-5p	CLIP-seq
MIRT2594877	hsa-miR-4795-3p	CLIP-seq
MIRT2594878	hsa-miR-496	CLIP-seq
MIRT2594879	hsa-miR-500b	CLIP-seq
MIRT2594880	hsa-miR-501-5p	CLIP-seq
MIRT2594881	hsa-miR-5047	CLIP-seq
MIRT2594882	hsa-miR-505	CLIP-seq
MIRT2594883	hsa-miR-518a-5p	CLIP-seq
MIRT2594884	hsa-miR-527	CLIP-seq
MIRT2594885	hsa-miR-575	CLIP-seq
MIRT2594886	hsa-miR-579	CLIP-seq
MIRT2594887	hsa-miR-605	CLIP-seq
MIRT2594888	hsa-miR-633	CLIP-seq
MIRT2594889	hsa-miR-770-5p	CLIP-seq
MIRT2594890	hsa-miR-891b	CLIP-seq
MIRT2594860	hsa-miR-1183	CLIP-seq
MIRT2594862	hsa-miR-145	CLIP-seq
MIRT2594864	hsa-miR-362-5p	CLIP-seq
MIRT2594865	hsa-miR-3647-3p	CLIP-seq
MIRT2594869	hsa-miR-383	CLIP-seq
MIRT2594870	hsa-miR-433	CLIP-seq
MIRT2594872	hsa-miR-4676-5p	CLIP-seq
MIRT2594875	hsa-miR-4769-3p	CLIP-seq
MIRT2594876	hsa-miR-4772-5p	CLIP-seq
MIRT2594878	hsa-miR-496	CLIP-seq
MIRT2594879	hsa-miR-500b	CLIP-seq
MIRT2594880	hsa-miR-501-5p	CLIP-seq
MIRT2594883	hsa-miR-518a-5p	CLIP-seq
MIRT2594884	hsa-miR-527	CLIP-seq
MIRT2594885	hsa-miR-575	CLIP-seq
MIRT2594887	hsa-miR-605	CLIP-seq
MIRT2594890	hsa-miR-891b	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IDA	11375391
GO:0000139	Component	Golgi membrane	IEA
GO:0001516	Process	Prostaglandin biosynthetic process	IDA	27642067
GO:0001516	Process	Prostaglandin biosynthetic process	IEA
GO:0001516	Process	Prostaglandin biosynthetic process	IMP	18451993
GO:0002827	Process	Positive regulation of T-helper 1 type immune response	IEA
GO:0004620	Function	Phospholipase activity	IEA
GO:0004622	Function	Phosphatidylcholine lysophospholipase activity	IDA	12672805, 16617059, 27642067
GO:0004622	Function	Phosphatidylcholine lysophospholipase activity	IEA
GO:0004623	Function	Phospholipase A2 activity	IDA	8702602
GO:0004623	Function	Phospholipase A2 activity	IEA
GO:0004623	Function	Phospholipase A2 activity	NAS	8381049
GO:0005509	Function	Calcium ion binding	IBA
GO:0005509	Function	Calcium ion binding	IDA	9430701, 9665851
GO:0005509	Function	Calcium ion binding	IEA
GO:0005544	Function	Calcium-dependent phospholipid binding	IBA
GO:0005544	Function	Calcium-dependent phospholipid binding	IDA	9665851
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005635	Component	Nuclear envelope	IDA	11375391
GO:0005635	Component	Nuclear envelope	IEA
GO:0005737	Component	Cytoplasm	IDA	11375391
GO:0005737	Component	Cytoplasm	IEA
GO:0005743	Component	Mitochondrial inner membrane	TAS
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005794	Component	Golgi apparatus	IBA
GO:0005794	Component	Golgi apparatus	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	NAS	8381049
GO:0005829	Component	Cytosol	TAS
GO:0006071	Process	Glycerol metabolic process	IEA
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006631	Process	Fatty acid metabolic process	IEA
GO:0006633	Process	Fatty acid biosynthetic process	IEA
GO:0006640	Process	Monoacylglycerol biosynthetic process	IDA	7794891
GO:0006650	Process	Glycerophospholipid metabolic process	IEA
GO:0006663	Process	Platelet activating factor biosynthetic process	IEA
GO:0006663	Process	Platelet activating factor biosynthetic process	NAS	9430701
GO:0006690	Process	Icosanoid metabolic process	NAS	9430701
GO:0006693	Process	Prostaglandin metabolic process	IEA
GO:0008289	Function	Lipid binding	IEA
GO:0008374	Function	O-acyltransferase activity	IDA	7794891
GO:0009395	Process	Phospholipid catabolic process	IEA
GO:0010314	Function	Phosphatidylinositol-5-phosphate binding	IDA	12672805
GO:0010572	Process	Positive regulation of platelet activation	IMP	18451993
GO:0016020	Component	Membrane	IEA
GO:0016042	Process	Lipid catabolic process	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0019369	Process	Arachidonate metabolic process	IDA	7794891
GO:0019369	Process	Arachidonate metabolic process	IEA
GO:0019369	Process	Arachidonate metabolic process	TAS	19718435
GO:0019370	Process	Leukotriene biosynthetic process	IEA
GO:0019370	Process	Leukotriene biosynthetic process	IMP	18451993
GO:0032266	Function	Phosphatidylinositol-3-phosphate binding	IDA	12672805
GO:0032308	Process	Positive regulation of prostaglandin secretion	IEA
GO:0034478	Process	Phosphatidylglycerol catabolic process	IDA	9425121
GO:0034638	Process	Phosphatidylcholine catabolic process	IDA	7794891, 9425121, 12672805, 14709560, 17472963
GO:0034638	Process	Phosphatidylcholine catabolic process	IEA
GO:0036151	Process	Phosphatidylcholine acyl-chain remodeling	IDA	16617059
GO:0042127	Process	Regulation of cell population proliferation	IEA
GO:0043032	Process	Positive regulation of macrophage activation	IEA
GO:0046456	Process	Icosanoid biosynthetic process	IEA
GO:0046475	Process	Glycerophospholipid catabolic process	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0047498	Function	Calcium-dependent phospholipase A2 activity	IBA
GO:0047498	Function	Calcium-dependent phospholipase A2 activity	IDA	7794891, 9425121, 14709560, 16617059, 17472963
GO:0047498	Function	Calcium-dependent phospholipase A2 activity	IEA
GO:0047498	Function	Calcium-dependent phospholipase A2 activity	IMP	18451993
GO:0047498	Function	Calcium-dependent phospholipase A2 activity	TAS
GO:0047499	Function	Calcium-independent phospholipase A2 activity	IDA	12672805
GO:0050482	Process	Arachidonate secretion	IEA
GO:0051649	Process	Establishment of localization in cell	IEA
GO:0052689	Function	Carboxylic ester hydrolase activity	IEA
GO:0070273	Function	Phosphatidylinositol-4-phosphate binding	IDA	12672805
GO:0071236	Process	Cellular response to antibiotic	IEA
GO:1902387	Function	Ceramide 1-phosphate binding	IDA	17472963

Other IDs

• MIM: 600522
• HGNC: 9035
• e!Ensembl: ENSG00000116711

Protein

• UniProt ID: P47712
• Protein name: Cytosolic phospholipase A2 (cPLA2) (Phospholipase A2 group IVA) [Includes: Phospholipase A2 (EC 3.1.1.4) (Phosphatidylcholine 2-acylhydrolase); Lysophospholipase (EC 3.1.1.5)]
• Protein function: Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, P
• PDB: 1BCI, 1CJY, 1RLW
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00168	C2	18 → 123	C2 domain	Domain
  PF01735	PLA2_B	190 → 675	Lysophospholipase catalytic domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in various cells and tissues such as macrophages, neutrophils, fibroblasts and lung endothelium. Expressed in platelets (at protein level) (PubMed:25102815). {ECO:0000269|PubMed:25102815}.
• Sequence:

  MSFIDPYQHIIVEHQYSHKFTVVVLRATKVTKGAFGDMLDTPDPYVELFISTTPDSRKRT
  RHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVMDETLGTATFTVSSMKVGEKKEV
  PFIFNQVTEMVLEMSLEVCSCPDLRFSMALCDQEKTFRQQRKEHIRESMKKLLGPKNSEG
  LHSARDVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSH
  PDFPEKGPEEINEELMKNVSHNPLLLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIG
  ETLIHNRMNTTLSSLKEKVNTAQCPLPLFTCLHVKPDVSELMFADWVEFSPYEIGMAKYG
  TFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVLGVSGSQSRGSTMEEE
  LENITTKHIVSNDSSDSDDESHEPKGTENEDAGSDYQSDNQASWIHRMIMALVSDSALFN
  TREGRAGKVHNFMLGLNLNTSYPLSPLSDFATQDSFDDDELDAAVADPDEFERIYEPLDV
  KSKKIHVVDSGLTFNLPYPLILRPQRGVDLIISFDFSARPSDSSPPFKELLLAEKWAKMN
  KLPFPKIDPYVFDREGLKECYVFKPKNPDMEKDCPTIIHFVLANINFRKYRAPGVPRETE
  EEKEIADFDIFDDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRR
  QNPSRCSVSLSNVEARRFFNKEFLSKPKA

• Sequence length: 749

Pathways

KEGG:

Glycerophospholipid metabolism
Ether lipid metabolism
Arachidonic acid metabolism
Linoleic acid metabolism
alpha-Linolenic acid metabolism
Metabolic pathways
MAPK signaling pathway
Ras signaling pathway
Phospholipase D signaling pathway
Necroptosis
Vascular smooth muscle contraction
VEGF signaling pathway
Platelet activation
Fc epsilon RI signaling pathway
Fc gamma R-mediated phagocytosis
Glutamatergic synapse
Serotonergic synapse
Long-term depression
Inflammatory mediator regulation of TRP channels
GnRH signaling pathway
Ovarian steroidogenesis
Oxytocin signaling pathway
Choline metabolism in cancer

Reactome:

phospho-PLA2 pathway
Acyl chain remodelling of PC
Acyl chain remodeling of CL
Acyl chain remodelling of PS
Acyl chain remodelling of PE
Acyl chain remodelling of PI
Acyl chain remodelling of PG
Hydrolysis of LPC
Synthesis of PA
Arachidonic acid metabolism
ADP signalling through P2Y purinoceptor 1
Platelet sensitization by LDL
COPI-independent Golgi-to-ER retrograde traffic

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder	Pathogenic	rs121434634, rs121434635, rs1557895416, rs1557901999, rs1571392612	RCV000009647 RCV000009648 RCV000766189 RCV000766190 RCV000995604

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign	rs6661772	RCV005928627
Colon adenocarcinoma	Benign	rs6661772	RCV005928626
Colorectal cancer	Benign	rs6661772	RCV005928628
PLA2G4A-related disorder	Benign; Likely benign	rs577639985, rs139670416, rs1656057711, rs896903466, rs34758865, rs12720687	RCV003916637 RCV003936500 RCV003923917 RCV003962034 RCV003968178 RCV003928580
Uterine corpus endometrial carcinoma	Benign	rs6661772	RCV005928629

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma	Stimulate	21198294
Alzheimer Disease	Associate	16151530
Alzheimer Disease	Stimulate	22832605
Arthritis Rheumatoid	Inhibit	24349530
Arthritis Rheumatoid	Associate	25893499
Asthma	Associate	17672871, 18665843
Astrocytoma	Associate	10501211
Atherosclerosis	Associate	11897617, 21293878
Autoimmune enteropathy	Associate	19148786, 30065566
Bipolar Disorder	Stimulate	20038946
Breast Neoplasms	Associate	20211985, 21119660, 37773865
Bronchopulmonary Dysplasia	Associate	37060021
Carcinogenesis	Associate	30829552, 31569627
Carcinoma Hepatocellular	Associate	11897617, 15294900, 26779633
Carcinoma Non Small Cell Lung	Associate	11559711, 18025046, 21198294, 9169405
Carcinoma Non Small Cell Lung	Stimulate	23049921
Cardiovascular Diseases	Associate	22378731
Celiac Disease	Associate	19237603
Cholangiocarcinoma	Associate	16966336, 18636547, 31492557
Chronic Disease	Associate	25893499
Cognition Disorders	Stimulate	22832605
Colitis Ulcerative	Associate	30065566
Colorectal Neoplasms	Associate	20635443
Congenital Hereditary and Neonatal Diseases and Abnormalities	Associate	36480694
Coronary Artery Disease	Associate	21293878
Cysts	Associate	31009406
Death	Associate	21293878
Diabetes Mellitus	Associate	11897617
Exfoliation Syndrome	Associate	17417602
Glioblastoma	Associate	34131250
Heart Diseases	Associate	21293878
Helicobacter Infections	Stimulate	11500464
Hematologic Neoplasms	Associate	34946532
Hypoxia	Inhibit	12874281
Inflammation	Associate	21198294, 21862584, 23646189, 23814065, 24069158, 24349530, 24441870, 25893499, 29273672, 33596205, 35011613, 7862535
Intestinal Diseases	Associate	30065566
Leiomyoma	Associate	30196971
Leukemia Myeloid Acute	Associate	33536020, 34502319, 36046688, 37367830, 38022627
Liver Cirrhosis Biliary	Associate	24349530
Lung Diseases	Associate	10749741
Lung Neoplasms	Associate	31347609
Lymphangioleiomyomatosis	Associate	37773865
Metabolic Diseases	Associate	11897617
Multiple Myeloma	Associate	34946532
Myocardial Infarction	Associate	21293878, 22378731
Necrosis	Inhibit	20211985
Neoplasm Metastasis	Associate	31003849, 31492557, 31569627
Neoplasms	Associate	11500464, 15294900, 19088022, 20635443, 21119660, 21198294, 23145155, 24553122, 30829552, 31003849, 31347609, 31569627, 34667273, 34946532
Neoplasms	Stimulate	31253108
Neurotoxicity Syndromes	Associate	20382209
Obesity	Associate	11897617
Osteoarthritis Knee	Associate	18471798
Osteosarcoma	Associate	31003849
Ovarian Neoplasms	Associate	24721622
Pancreatic Cyst	Associate	31009406
Post Acute COVID 19 Syndrome	Associate	36890149
Prostaglandin Endoperoxide Synthase 1 Deficiency Platelet	Associate	19148786
Prostatic Neoplasms	Associate	19088022, 23646189, 35089606
Respiratory Tract Diseases	Associate	21391979
Sertoli Cell Only Syndrome	Associate	37296437
Status Asthmaticus	Associate	18665843
Stroke	Associate	21293878
Systemic Inflammatory Response Syndrome	Associate	15802794
Ulcer	Associate	19148786
Urethral Neoplasms	Associate	23145155
Uterine Cervical Neoplasms	Stimulate	30829552
Vitiligo	Associate	36890149