RNASEH2A Gene

Name	ribonuclease H2, subunit A
Description	The protein encoded by this gene is a component of the heterotrimeric type II ribonuclease H enzyme (RNAseH2). RNAseH2 is the major source of ribonuclease H activity in mammalian cells and endonucleolytically cleaves ribonucleotides. It is predicted to remove Okazaki fragment RNA primers during lagging strand DNA synthesis and to excise single ribonucleotides from DNA-DNA duplexes. Mutations in this gene cause Aicardi-Goutieres Syndrome (AGS), a an autosomal recessive neurological disorder characterized by progressive microcephaly and psychomotor retardation, intracranial calcifications, elevated levels of interferon-alpha and white blood cells in the cerebrospinal fluid.[provided by RefSeq, Aug 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNASEH2A encodes the catalytic subunit of the RNase H2 complex—an enzyme essential for maintaining genomic homeostasis through the removal of misincorporated ribonucleotides and the resolution of RNA–DNA hybrids (R‐loops) generated during transcription and DNA replication. Dysfunctional RNASEH2A, whether by mutations that impair splicing or catalytic activity, disrupts the coordinated assembly and function of the RNase H2 heterotrimer, leading to the accumulation of R-loops and DNA damage. These alterations are central to the pathogenesis of Aicardi–Goutières syndrome (AGS), a neuroinflammatory disorder characterized by an aberrant interferon response, as demonstrated by structural and kinetic analyses of pathogenic mutations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its fundamental role in genome maintenance, RNASEH2A has emerged as an important factor in cancer biology. Dysregulated expression of RNASEH2A is reported in a variety of tumor types—including glioma, lung adenocarcinoma, cervical, ovarian, renal, and prostate cancers—where it promotes cell proliferation, sustains DNA replication fidelity, and facilitates repair processes such as PCNA‐mediated gap filling and non‐homologous end joining. Loss of RNASEH2A function renders tumor cells hypersensitive to replication stress and DNA damage, as evidenced by synthetic lethality with ATR inhibitors and delayed double‐strand break repair. Moreover, oncogenic viruses (e.g., high‐risk HPV) and regulatory networks involving microRNAs, long noncoding RNAs, and transcription factors like FOXA1 modulate RNASEH2A levels to promote neoplastic progression, while its altered expression has prognostic implications in cancers such as renal cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDownregulation of RNASEH2A is also implicated in cellular senescence and aging. Reduced RNASEH2A activity leads to the persistent presence of ribonucleotides and unresolved R-loops, which in turn cause genomic fragmentation and aberrant activation of cytosolic nucleic acid sensors. This cascade provokes the senescence-associated secretory phenotype (SASP), contributing to age-related pathologies and creating a microenvironment that may facilitate cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephanie R Coffin, Thomas Hollis, Fred W Perrino "}, {"type": "b", "children": [{"type": "t", "text": "Functional consequences of the RNase H2A subunit mutations that cause Aicardi-Goutieres syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.228833"}], "href": "https://doi.org/10.1074/jbc.M111.228833"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21454563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21454563"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gillian I Rice, Martin A M Reijns, Stephanie R Coffin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synonymous mutations in RNASEH2A create cryptic splice sites impairing RNase H2 enzyme function in Aicardi-Goutières syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22336"}], "href": "https://doi.org/10.1002/humu.22336"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23592335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23592335"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Barbara Kind, Britta Muster, Wolfgang Staroske, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered spatio-temporal dynamics of RNase H2 complex assembly at replication and repair sites in Aicardi-Goutières syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu319"}], "href": "https://doi.org/10.1093/hmg/ddu319"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24986920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24986920"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "John H Livingston, Yanick J Crow "}, {"type": "b", "children": [{"type": "t", "text": "Neurologic Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1: Aicardi-Goutières Syndrome and Beyond."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropediatrics (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-0036-1592307"}], "href": "https://doi.org/10.1055/s-0036-1592307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27643693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27643693"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Agnese Cristini, Michael Tellier, Flavia Constantinescu, et al. 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Synonyms	RNHL, JUNB, RNHIA, AGS4, RNASEHI, THSD8
Proteins	RNH2A_HUMAN
NCBI Gene ID	10535
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RNASEH2A has 10,064 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 RNASEH2A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RNASEH2A 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 RNASEH2A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RNASEH2A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RNASEH2A 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 RNASEH2A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RNASEH2A 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 RNASEH2A 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 RNASEH2A gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with RNASEH2A gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RNASEH2A protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RNASEH2A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RNASEH2A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RNASEH2A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RNASEH2A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RNASEH2A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RNASEH2A 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 RNASEH2A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving RNASEH2A gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RNASEH2A gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with RNASEH2A 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 RNASEH2A 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 RNASEH2A 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 RNASEH2A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RNASEH2A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.