POLG2 Gene

HGNC Family	Polymerases, DNA-directed (POL)
Name	polymerase (DNA directed), gamma 2, accessory subunit
Description	This gene encodes the processivity subunit of the mitochondrial DNA polymerase gamma. The encoded protein forms a heterotrimer containing one catalytic subunit and two processivity subunits. This protein enhances DNA binding and promotes processive DNA synthesis. Mutations in this gene result in autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions.[provided by RefSeq, Sep 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe POLG2 gene encodes the accessory subunit (p55) of mitochondrial DNA polymerase gamma, which plays an essential role in mtDNA replication by enhancing processivity and stabilizing the catalytic subunit (POLGα). This accessory subunit not only increases the polymerase’s substrate affinity via its dimerization but also contributes to the proper organization of mitochondrial nucleoids. Its ability to preferentially bind structured DNA—such as duplex regions with displacement-loop features—underscores its role as both a processivity factor and a mediator of higher order mtDNA packaging."}, {"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": "\nMutations in POLG2 have been directly linked to a spectrum of mitochondrial disorders. Several studies have identified heterozygous and homozygous missense variants—as well as truncating mutations—that impair the interaction of POLG2 with the catalytic subunit, diminish processive DNA synthesis, or disrupt dimerization required for proper DNA binding. These mutations have been associated with clinical phenotypes ranging from adult-onset progressive external ophthalmoplegia (adPEO) to severe neonatal mtDNA depletion syndromes manifesting as hepatic failure. Biochemical analyses of recombinant mutant proteins further elucidate defects in subunit interaction and complex stability that underlie the pathogenesis of POLG2-related mitochondrial diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond primary mitochondrial maintenance, genetic polymorphisms and regulatory variations in POLG2 have been implicated in broader pathophysiological contexts, including associations with altered mtDNA content, cancer, and even chronic disease risk factors. Genetic association studies highlight that specific single-nucleotide polymorphisms in POLG2 correlate with conditions such as oral leukoplakia, invasive bladder cancer, and may even modulate risk in complex disease phenotypes. These observations suggest that modulation of POLG2 expression and function can significantly impact mitochondrial integrity and thereby influence cell metabolism and disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural studies of POLG2 further reveal that its DNA binding is mediated by distinct surface loops and oligomeric interfaces that are critical for its function. The two DNA binding modes identified—dimeric and hexameric assemblies—suggest that POLG2 plays roles beyond simple processivity enhancement by targeting specific DNA structures like forked configurations at the mitochondrial D-loop. Such structural insights not only provide a molecular explanation for its dual functional roles but also clarify how disruptions in these interfaces can contribute to mitochondrial pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M Di Re, H Sembongi, J He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The accessory subunit of mitochondrial DNA polymerase gamma determines the DNA content of mitochondrial nucleoids in human cultured cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkp614"}], "href": "https://doi.org/10.1093/nar/gkp614"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19625489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19625489"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Young-Sam Lee, Sujin Lee, Borries Demeler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Each monomer of the dimeric accessory protein for human mitochondrial DNA polymerase has a distinct role in conferring processivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.062752"}], "href": "https://doi.org/10.1074/jbc.M109.062752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19858216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19858216"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yura Do, Shigeru Matsuda, Teppei Inatomi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The accessory subunit of human DNA polymerase γ is required for mitochondrial DNA maintenance and is able to stabilize the catalytic subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2020.05.008"}], "href": "https://doi.org/10.1016/j.mito.2020.05.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32470614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32470614"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Stefan Michiels, Patrick Danoy, Philippe Dessen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphism discovery in 62 DNA repair genes and haplotype associations with risks for lung and head and neck cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgm111"}], "href": "https://doi.org/10.1093/carcin/bgm111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17494052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17494052"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Matthew J Young, Matthew J Longley, Fang-Yuan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biochemical analysis of human POLG2 variants associated with mitochondrial disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddr209"}], "href": "https://doi.org/10.1093/hmg/ddr209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21555342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21555342"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rajesh Kasiviswanathan, Matthew J Longley, Sherine S L Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disease mutations in the human mitochondrial DNA polymerase thumb subdomain impart severe defects in mitochondrial DNA replication."}]}, {"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.M109.011940"}], "href": "https://doi.org/10.1074/jbc.M109.011940"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19478085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19478085"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kate Craig, Matthew J Young, Emma L Blakely, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A p.R369G POLG2 mutation associated with adPEO and multiple mtDNA deletions causes decreased affinity between polymerase γ subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2011.11.006"}], "href": "https://doi.org/10.1016/j.mito.2011.11.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22155748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22155748"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hemant Varma, Phyllis L Faust, Alejandro D Iglesias, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole exome sequencing identifies a homozygous POLG2 missense variant in an infant with fulminant hepatic failure and mitochondrial DNA depletion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2016.08.012"}], "href": "https://doi.org/10.1016/j.ejmg.2016.08.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27592148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27592148"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kirsten E Hoff, Karen L DeBalsi, Maria J Sanchez-Quintero, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "POLG2-Linked Mitochondrial Disease: Functional Insights from New Mutation Carriers and Review of the Literature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cerebellum (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12311-023-01557-x"}], "href": "https://doi.org/10.1007/s12311-023-01557-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37085601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37085601"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hongjin Huang, Mitchell L Shiffman, Ramsey C Cheung, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial DNA content contributes to healthy aging in Chinese: a study from nonagenarians and centenarians."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2014.01.015"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2014.01.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24524965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24524965"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Roberta Virgilio, Dario Ronchi, Georgios M Hadjigeorgiou, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Association of DNA sequence variation in mitochondrial DNA polymerase with mitochondrial DNA synthesis and risk of oral cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2015.09.039"}], "href": "https://doi.org/10.1016/j.gene.2015.09.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26403317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26403317"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Chanavee Ratanajaraya, Hiroyuki Nishiyama, Meiko Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A polymorphism of the POLG2 gene is genetically associated with the invasiveness of urinary bladder cancer in Japanese males."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2011.60"}], "href": "https://doi.org/10.1038/jhg.2011.60"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21734712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21734712"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "José A Carrodeguas, Kevin G Pinz, Daniel F Bogenhagen "}, {"type": "b", "children": [{"type": "t", "text": "DNA binding properties of human pol gammaB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207030200"}], "href": "https://doi.org/10.1074/jbc.M207030200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12379656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12379656"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jessica L Wojtaszek, Kirsten E Hoff, Matthew J Longley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure-specific roles for PolG2-DNA complexes in maintenance and replication of mitochondrial DNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkad679"}], "href": "https://doi.org/10.1093/nar/gkad679"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37592734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37592734"}]}]}]}
Synonyms	MTPOLB, HP55, POLB, POLGB, POLG-BETA, PEOA4
Proteins	DPOG2_HUMAN
NCBI Gene ID	11232
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

POLG2 has 8,724 functional associations with biological entities spanning 9 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, sequence feature) extracted from 122 datasets.

Click the + buttons to view associations for POLG2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

POLG2 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 POLG2 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 POLG2 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 POLG2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse 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 POLG2 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 POLG2 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 POLG2 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 POLG2 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 POLG2 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 POLG2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of POLG2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of POLG2 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 POLG2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with POLG2 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of POLG2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of POLG2 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 POLG2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with POLG2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with POLG2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing POLG2 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 POLG2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing POLG2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing POLG2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing POLG2 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 POLG2 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 POLG2 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 POLG2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with POLG2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with POLG2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by POLG2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving POLG2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving POLG2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with POLG2 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 POLG2 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 POLG2 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 POLG2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with POLG2 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 POLG2 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 POLG2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of POLG2 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 POLG2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.