PLAA Gene

HGNC Family	WD repeat domain containing (WDR)
Name	phospholipase A2-activating protein
Description	Predicted to enable ubiquitin binding activity. Involved in cellular response to lipopolysaccharide; macroautophagy; and positive regulation of phospholipase A2 activity. Located in cytoplasm; extracellular exosome; and nucleus. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPLAA is a multifunctional signaling and regulatory protein that orchestrates inflammatory and lipid metabolic processes. It facilitates the activation of cytosolic phospholipase A₂, thereby promoting the synthesis of key mediators such as prostaglandin E₂ and interleukins in response to cytokines like TNF-α, as well as mediating rapid membrane-initiated actions of 1α,25-dihydroxy vitamin D₃. These activities depend on its capacity to engage ubiquitin signaling pathways via a novel ubiquitin‐binding PFUC domain, which links PLAA to broader protein quality control and inflammatory cascades."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, PLAA is critical for maintaining cellular homeostasis. It cooperates with the ubiquitin-directed AAA‑ATPase p97 to promote the autophagic clearance of damaged lysosomes by selectively removing specific ubiquitin conjugates, a function that prevents the aberrant accumulation of ubiquitinated proteins at synapses and thereby supports proper synaptic vesicle recycling and neurotransmission. Genetic studies have further implicated PLAA as a susceptibility factor in schizophrenia, and its loss-of-function is linked to severe neurodevelopmental leukoencephalopathy characterized by impaired prostaglandin E₂ and cytosolic PLA₂ synthesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOutside the central nervous system, diminished PLAA expression has been associated with enhanced metastatic behavior in ovarian cancer. In this context, PLAA appears to restrain cell migration and invasion by modulating a METTL3–TRPC3 axis that regulates intracellular Ca²⁺ signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fan Zhang, Jian Sha, Thomas G Wood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alteration in the activation state of new inflammation-associated targets by phospholipase A2-activating protein (PLAA)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2008.01.004"}], "href": "https://doi.org/10.1016/j.cellsig.2008.01.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18291623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18291623"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qing-Shan Fu, Chen-Jie Zhou, Hong-Chang Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for ubiquitin recognition by a novel domain from human phospholipase A2-activating protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.009126"}], "href": "https://doi.org/10.1074/jbc.M109.009126"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19423704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19423704"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Maryam Doroudi, Zvi Schwartz, Barbara D Boyan "}, {"type": "b", "children": [{"type": "t", "text": "Membrane-mediated actions of 1,25-dihydroxy vitamin D3: a review of the roles of phospholipase A2 activating protein and Ca(2+)/calmodulin-dependent protein kinase II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Steroid Biochem Mol Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jsbmb.2014.11.002"}], "href": "https://doi.org/10.1016/j.jsbmb.2014.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25448737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25448737"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lavinia Athanasiu, Morten Mattingsdal, Anna K Kähler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Psychiatr Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jpsychires.2010.02.002"}], "href": "https://doi.org/10.1016/j.jpsychires.2010.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20185149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20185149"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chrisovalantis Papadopoulos, Philipp Kirchner, Monika Bug, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201695148"}], "href": "https://doi.org/10.15252/embj.201695148"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27753622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27753622"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tzipora C Falik Zaccai, David Savitzki, Yifat Zivony-Elboum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/aww295"}], "href": "https://doi.org/10.1093/brain/aww295"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28007986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28007986"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Emma A Hall, Michael S Nahorski, Lyndsay M Murray, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLAA Mutations Cause a Lethal Infantile Epileptic Encephalopathy by Disrupting Ubiquitin-Mediated Endolysosomal Degradation of Synaptic Proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2017.03.008"}], "href": "https://doi.org/10.1016/j.ajhg.2017.03.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28413018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28413018"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zhangjin Shen, Lingkai Gu, Yuwan Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLAA suppresses ovarian cancer metastasis via METTL3-mediated m"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "6"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "A modification of TRPC3 mRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-022-02411-w"}], "href": "https://doi.org/10.1038/s41388-022-02411-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35869392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35869392"}]}]}]}
Synonyms	PLA2P, NDMSBA, DOA1
Proteins	PLAP_HUMAN
NCBI Gene ID	9373
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PLAA has 6,343 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 121 datasets.

Click the + buttons to view associations for PLAA from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PLAA Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PLAA gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PLAA gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PLAA gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PLAA gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PLAA gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PLAA gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PLAA gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PLAA gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PLAA gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PLAA gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PLAA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PLAA protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PLAA gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PLAA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PLAA gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PLAA gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PLAA gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PLAA protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PLAA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PLAA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PLAA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PLAA protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PLAA protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PLAA protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PLAA protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PLAA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PLAA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PLAA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PLAA gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PLAA gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PLAA gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PLAA gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PLAA gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PLAA gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PLAA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PLAA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PLAA gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PLAA gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PLAA gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PLAA from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.