PNPLA8 Gene

HGNC Family	Patatin-like phospholipase domain containing (PNPLA)
Name	patatin-like phospholipase domain containing 8
Description	This gene encodes a member of the patatin-like phospholipase domain containing protein family. Members of this family are phospholipases which catalyze the cleavage of fatty acids from membrane phospholipids. The product of this gene is a calcium-independent phospholipase. Mutations in this gene have been associated with mitochondrial myopathy with lactic acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPNPLA8, also known as group VIB calcium‐independent phospholipase A2γ (iPLA2γ), plays a central role in cellular lipid homeostasis by catalyzing the hydrolysis of specific phospholipid substrates. In various cell types, PNPLA8 liberates arachidonic acid (AA) that is subsequently converted into bioactive eicosanoids such as prostaglandin E2, linking its activity to signaling pathways that regulate cell growth and inflammatory responses. This function has been demonstrated in cell models where overexpression of iPLA2γ led to increased spontaneous and stimulus‐coupled AA release and prostaglandin synthesis, suggesting its involvement in tumorigenesis as observed in colorectal cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cardiac physiology, PNPLA8 is implicated in the remodeling of mitochondrial phospholipid metabolism. In failing myocardium, enhanced iPLA2γ activity redirects AA metabolism toward the production of toxic hydroxyeicosatetraenoic acids (HETEs) that promote mitochondrial permeability transition pore opening, necrosis, and apoptosis. Conversely, under non‐pathological conditions and during acute stress such as Trypanosoma cruzi infection, activation of PNPLA8 contributes to the generation of protective eicosanoids that support cardiomyocyte survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn platelets and renal glomerular epithelial cells, PNPLA8 functions as a key mediator of membrane phospholipid remodeling. In platelets, its enzymatic action is vital for the generation of pro‐thrombotic eicosanoids such as thromboxane A2 and novel eicosanoid–lysophospholipids that are produced via oxidation by 12-lipoxygenase, thereby facilitating platelet aggregation and thrombosis. Moreover, in glomerular epithelial cells, activation of iPLA2γ by complement components engages MAP kinase signaling cascades via phosphorylation events, leading to the release of prostaglandin E2 and contributing to cytoprotective responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have revealed that PNPLA8 is essential for proper neurodevelopment and mitochondrial function in the nervous system. Biallelic loss-of-function variants in PNPLA8 have been associated with a broad spectrum of pediatric neurodegenerative disorders that include congenital microcephaly, global developmental delay, spasticity, and progressive cerebellar atrophy. Investigations using cerebral organoids derived from patient-induced pluripotent stem cells indicate that PNPLA8 deficiency disrupts the production and fate specification of basal radial glial cells, likely due to altered phospholipid composition, thereby impairing proper brain development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence further suggests that aberrant PNPLA8 activity may be linked to oncogenic processes. Aside from its established role in colorectal cancer models, the importance of phospholipase-mediated lipid remodeling in aggressive malignancies such as triple-negative breast cancer is being increasingly recognized, highlighting PNPLA8 as a potential biomarker and therapeutic target in age-related and proliferative diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Makoto Murakami, Seiko Masuda, Kaori Ueda-Semmyo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Group VIB Ca2+-independent phospholipase A2gamma promotes cellular membrane hydrolysis and prostaglandin production in a manner distinct from other intracellular phospholipases A2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M413766200"}], "href": "https://doi.org/10.1074/jbc.M413766200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15695510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15695510"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sung Ho Moon, Xinping Liu, Ari M Cedars, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heart failure-induced activation of phospholipase iPLA"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA117.000405"}], "href": "https://doi.org/10.1074/jbc.RA117.000405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29158256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29158256"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Janhavi Sharma, Christopher S Eickhoff, Daniel F Hoft, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The absence of myocardial calcium-independent phospholipase A2γ results in impaired prostaglandin E2 production and decreased survival in mice with acute Trypanosoma cruzi infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/IAI.00497-12"}], "href": "https://doi.org/10.1128/IAI.00497-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23429536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23429536"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hanan Elimam, Joan Papillon, Tomoko Takano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complement-mediated activation of calcium-independent phospholipase A2γ: role of protein kinases and phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.396614"}], "href": "https://doi.org/10.1074/jbc.M112.396614"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23258543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23258543"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Emiko Yoda, Kohmi Rai, Mai Ogawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Group VIB calcium-independent phospholipase A2 (iPLA2γ) regulates platelet activation, hemostasis and thrombosis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0109409"}], "href": "https://doi.org/10.1371/journal.pone.0109409"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25313821"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25313821"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xinping Liu, Harold F Sims, Christopher M Jenkins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "γ knockout."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.012296"}], "href": "https://doi.org/10.1074/jbc.RA119.012296"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32161117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32161117"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anju Shukla, Russell P Saneto, Malavika Hebbar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A neurodegenerative mitochondrial disease phenotype due to biallelic loss-of-function variants in PNPLA8 encoding calcium-independent phospholipase A2γ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.38687"}], "href": "https://doi.org/10.1002/ajmg.a.38687"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29681094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29681094"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yuji Nakamura, Issei S Shimada, Reza Maroofian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic null variants in PNPLA8 cause microcephaly by reducing the number of basal radial glia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awae185"}], "href": "https://doi.org/10.1093/brain/awae185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39082157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39082157"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zheqiong Tan, Pragney Deme, Keerti Boyapati, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-023-01742-0"}], "href": "https://doi.org/10.1186/s13058-023-01742-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38017485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38017485"}]}]}]}
Synonyms	IPLA2GAMMA, IPLA2-2, MMLA, IPLA2(GAMMA), PNPLA-gamma, IPLA2G
Proteins	PLPL8_HUMAN
NCBI Gene ID	50640
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PNPLA8 has 4,604 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 109 datasets.

Click the + buttons to view associations for PNPLA8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PNPLA8 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PNPLA8 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PNPLA8 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PNPLA8 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 PNPLA8 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 PNPLA8 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PNPLA8 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PNPLA8 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PNPLA8 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 PNPLA8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PNPLA8 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PNPLA8 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 PNPLA8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PNPLA8 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 PNPLA8 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PNPLA8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PNPLA8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PNPLA8 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 PNPLA8 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 PNPLA8 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 PNPLA8 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 PNPLA8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PNPLA8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PNPLA8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PNPLA8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PNPLA8 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PNPLA8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PNPLA8 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PNPLA8 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 PNPLA8 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 PNPLA8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PNPLA8 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 PNPLA8 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 PNPLA8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PNPLA8 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 PNPLA8 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PNPLA8 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PNPLA8 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing PNPLA8 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of PNPLA8 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of PNPLA8 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.