POLH Gene

Name	polymerase (DNA directed), eta
Description	This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class switch recombination. Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nDNA polymerase η (POLH) is a specialized Y‐family enzyme that facilitates translesion synthesis (TLS) by efficiently bypassing ultraviolet‐induced DNA lesions—particularly cyclobutane pyrimidine dimers—with a surprisingly high in vivo fidelity. Detailed biochemical analyses have demonstrated that POLH is uniquely capable of copying damaged DNA by maintaining a “molecular splint” conformation that stabilizes the lesion in a near–B‐form geometry, thereby allowing two–metal ion catalysis even at sites of distortion. Its error specificity has been characterized, revealing increased mutagenesis at the 3′ thymine of a dimer and even a propensity for tandem base substitutions when copying normal DNA."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMolecular studies have revealed that POLH function is tightly regulated by its interactions with proliferating cell nuclear antigen (PCNA) and ubiquitin. The presence of specialized ubiquitin‐binding motifs (UBZ and UBM) in POLH and other Y–family polymerases enables their recruitment to stalled replication forks through monoubiquitinated PCNA, coordinating the polymerase switch from high–fidelity replicases to TLS polymerases. In vitro and cellular localization experiments confirm that these domains are essential for POLH’s assembly into replication foci and for restoring normal UV–response in xeroderma pigmentosum variant cells. Moreover, kinetic analyses emphasize its moderate processivity and intrinsic error rate when copying undamaged DNA."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in bypassing UV–induced lesions, POLH contributes to recombination–independent repair pathways for more complex DNA damage such as interstrand cross–links, with deficiencies in its function causing the human syndrome xeroderma pigmentosum variant (XPV). Its specialized structural configuration—featuring an enlarged active site that readily accommodates distorted DNA—underscores POLH’s critical role in preserving genome stability under replication stress. Such characteristics not only highlight POLH’s importance in minimizing mutagenesis during lesion bypass but also point to its potential as a therapeutic target to reduce mutagenic outcomes in response to DNA–damaging agents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T Matsuda, K Bebenek, C Masutani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Error rate and specificity of human and murine DNA polymerase eta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/jmbi.2001.4937"}], "href": "https://doi.org/10.1006/jmbi.2001.4937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11554790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11554790"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Patricia L Kannouche, Jonathan Wing, Alan R Lehmann "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(04)00259-x"}], "href": "https://doi.org/10.1016/s1097-2765(04"}, {"type": "t", "text": "00259-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15149598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15149598"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jung-Hoon Yoon, Louise Prakash, Satya Prakash "}, {"type": "b", "children": [{"type": "t", "text": "Highly error-free role of DNA polymerase eta in the replicative bypass of UV-induced pyrimidine dimers in mouse and human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0910121106"}], "href": "https://doi.org/10.1073/pnas.0910121106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19822754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19822754"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Christian Biertümpfel, Ye Zhao, Yuji Kondo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure and mechanism of human DNA polymerase eta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09196"}], "href": "https://doi.org/10.1038/nature09196"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20577208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20577208"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuan-Ji Day, Liping Huang, Hong Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00378.2004"}], "href": "https://doi.org/10.1152/ajprenal.00378.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15561971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15561971"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marzena Bienko, Catherine M Green, Nicola Crosetto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1120615"}], "href": "https://doi.org/10.1126/science.1120615"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16357261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16357261"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Brian S Plosky, Antonio E Vidal, Antonio R Fernández de Henestrosa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Controlling the subcellular localization of DNA polymerases iota and eta via interactions with ubiquitin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601178"}], "href": "https://doi.org/10.1038/sj.emboj.7601178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16763556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16763556"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Huyong Zheng, Xin Wang, Amy J Warren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nucleotide excision repair- and polymerase eta-mediated error-prone removal of mitomycin C interstrand cross-links."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.2.754-761.2003"}], "href": "https://doi.org/10.1128/MCB.23.2.754-761.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12509472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12509472"}]}]}]}
Synonyms	RAD30A, XPV, RAD30, XP-V
Proteins	POLH_HUMAN
NCBI Gene ID	5429
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

POLH has 7,068 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 126 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

POLH 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 POLH 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 POLH 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 POLH 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 POLH 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 POLH 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 POLH 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 POLH 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 POLH 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 POLH 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 POLH gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of POLH 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 POLH gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with POLH 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 POLH gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of POLH 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 POLH 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 POLH gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with POLH gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of POLH gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing POLH protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing POLH protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with POLH 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 POLH protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing POLH protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of POLH gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with POLH gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with POLH gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with POLH gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of POLH 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 POLH gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving POLH gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving POLH gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with POLH 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 POLH 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 POLH gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with POLH 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 POLH 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 POLH gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of POLH 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 POLH from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.