PLA2G4A

phospholipase A2 group IVA, the group of Phospholipases|C2 domain containing phospholipases

Basic information

Region (hg38): 1:186828949-186988981

Previous symbols: [ "PLA2G4" ]

Links

ENSG00000116711 ∙ NCBI:5321 ∙ OMIM:600522 ∙ HGNC:9035 ∙ Uniprot:P47712 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder (Strong), mode of inheritance: AR
• cryptogenic multifocal ulcerous stenosing enteritis (Supportive), mode of inheritance: AR
• cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder (Supportive), mode of inheritance: AR
• cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gastrointestinal ulceration, recurrent, with dysfunctional platelets	AR	Gastrointestinal; Hematologic	Surveillance for bleeding complications may be beneficial, as a described individual had chronic GI blood loss from childhood, with multiple small intestinal ulcers discovered in the context of severe bleeding and perforations during adulthood; Awareness of GI complications, including Cryptogenic multifocal ulcerating stenosing enteritis, as has been described in one pair of siblings, may allow early medical and/or surgical management	Gastrointestinal; Hematologic	18451993; 23268370

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLA2G4A gene.

• Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLA2G4A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				37	6	43
missense			31	5	5	41
nonsense						0
start loss						0
frameshift	1		2			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	7	3	11
non coding				23	4	27
Total	1	0	34	65	15

Variants in PLA2G4A

This is a list of pathogenic ClinVar variants found in the PLA2G4A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-186854369-T-C			Likely benign (Jan 26, 2024)
1-186854407-T-C			Likely benign (Jan 20, 2024)
1-186870464-G-A		PLA2G4A-related disorder	Likely benign (Aug 30, 2019)
1-186870478-G-A			Uncertain significance (Jul 06, 2022)
1-186870501-G-A		not specified	Uncertain significance (Oct 20, 2023)
1-186870519-A-AAG			Uncertain significance (Aug 07, 2022)
1-186870523-G-A			Likely benign (Jul 26, 2023)
1-186870526-C-G			Likely benign (Aug 02, 2018)
1-186870526-C-CT			Benign (Jul 25, 2023)
1-186870529-T-A			Benign (Dec 11, 2023)
1-186870532-T-A			Likely benign (Sep 12, 2022)
1-186870532-T-C			Likely benign (Jul 12, 2023)
1-186893004-T-C			Likely benign (Nov 22, 2023)
1-186893060-C-G			Uncertain significance (Apr 03, 2023)
1-186893095-T-C		not specified	Uncertain significance (Dec 20, 2023)
1-186893130-T-C			Likely benign (Mar 09, 2023)
1-186893141-T-C			Likely benign (Apr 17, 2018)
1-186893167-A-G			Likely benign (Sep 15, 2022)
1-186894126-T-C			Uncertain significance (Jun 20, 2022)
1-186894136-T-C			Likely benign (Apr 21, 2022)
1-186894142-G-C			Likely benign (Jul 22, 2023)
1-186894155-A-T			Likely benign (Apr 14, 2023)
1-186894164-T-C		Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder	Pathogenic (Jun 01, 2008)
1-186894188-G-A			Benign (Jan 18, 2024)
1-186906976-G-C		not specified	Uncertain significance (Jun 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLA2G4A	protein_coding	protein_coding	ENST00000367466	17	160029

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000598	1.00	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	265	397	0.667	0.0000198	5027
Missense in Polyphen		66	151.3	0.43621		1950
Synonymous	-0.0493	137	136	1.01	0.00000724	1338
Loss of Function	3.53	14	37.3	0.376	0.00000195	464

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000370	0.000370
European (Non-Finnish)	0.0000705	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.000261	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.
• Disease: DISEASE: Note=PLA2G4A mutations resulting in phospholipase A2 deficiency have been found in a patient affected by recurrent episodes of multiple complicated ulcers of the small intestine, not due to cyclooxygenase inhibitors use. Disease features also include platelet dysfunction, and globally decreased eicosanoid synthesis (PubMed:18451993). {ECO:0000269|PubMed:18451993}.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Ether lipid metabolism - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Glycerophospholipid metabolism - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Long-term depression - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Necroptosis - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);alpha-Linolenic acid metabolism - Homo sapiens (human);Arachidonic acid metabolism - Homo sapiens (human);Linoleic acid metabolism - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Leukotriene modifiers pathway, Pharmacodynamics;Fc Epsilon Receptor I Signaling in Mast Cells;AGE-RAGE pathway;Nanoparticle triggered regulated necrosis;PDGF Pathway;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;p38 MAPK Signaling Pathway;Ras Signaling;Prostaglandin Synthesis and Regulation;Signaling by GPCR;RAGE;Acyl chain remodelling of PI;Signal Transduction;Acyl chain remodelling of PG;Vesicle-mediated transport;aspirin blocks signaling pathway involved in platelet activation;Membrane Trafficking;Metabolism of lipids;Arachidonic acid metabolism;Metabolism;phospholipases;Fatty acid metabolism;Acyl chain remodelling of PC;Acyl chain remodeling of CL;Signal amplification;IL1;Platelet activation, signaling and aggregation;Linoleate metabolism;Glycerophospholipid metabolism;ADP signalling through P2Y purinoceptor 1;Acyl chain remodelling of PS;Hemostasis;COPI-independent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;phospho-PLA2 pathway;Ca-dependent events;PLC beta mediated events;G-protein mediated events;Glycerophospholipid biosynthesis;Phospholipid metabolism;Opioid Signalling;G alpha (i) signalling events;IL5;Hydrolysis of LPC;Acyl chain remodelling of PE;Synthesis of PA;Platelet sensitization by LDL;Platelet homeostasis;GPCR downstream signalling;Signaling mediated by p38-alpha and p38-beta;Fc-epsilon receptor I signaling in mast cells;PDGFR-beta signaling pathway;Endothelins;Arachidonic acid metabolism;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.448

Intolerance Scores

• loftool: 0.642
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.135
• hipred: Y
• hipred_score: 0.624
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.945

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pla2g4a
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; muscle phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype

Zebrafish Information Network

• Gene name: pla2g4aa
• Affected structure: otic vesicle
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: phospholipid metabolic process;phosphatidic acid biosynthetic process;platelet activating factor biosynthetic process;icosanoid metabolic process;arachidonic acid metabolic process;cardiolipin acyl-chain remodeling;phosphatidylglycerol acyl-chain remodeling;phosphatidylinositol acyl-chain remodeling;phosphatidylserine acyl-chain remodeling;phosphatidylcholine acyl-chain remodeling;phosphatidylethanolamine acyl-chain remodeling;regulation of cell population proliferation;icosanoid biosynthetic process;glycerophospholipid catabolic process;arachidonic acid secretion;cellular response to antibiotic
• Cellular component: nucleus;cytoplasm;mitochondrial inner membrane;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;lipid droplet;cytosol;cytoplasmic vesicle
• Molecular function: lysophospholipase activity;phospholipase A2 activity;calcium ion binding;calcium-dependent phospholipid binding;phospholipase A1 activity;calcium-dependent phospholipase A2 activity;phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine);phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine)