REXO2 Gene

HGNC Family	Exonucleases
Name	RNA exonuclease 2
Description	This gene encodes a 3'-to-5' exonuclease specific for small (primarily 5 nucleotides or less in length) single-stranded RNA and DNA oligomers. This protein may have a role in DNA repair, replication, and recombination, and in RNA processing and degradation. It may also be involved in resistance of human cells to UV-C-induced cell death through its role in the DNA repair process. [provided by RefSeq, Nov 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nREXO2 is a conserved 3′–to–5′ exonuclease that, as the human homolog of Escherichia coli oligoribonuclease, plays essential roles in cellular RNA turnover. In human cells, it exhibits a dual subcellular distribution with both cytosolic and mitochondrial localizations, where in mitochondria it is found in the intermembrane space and matrix. Depletion of REXO2 causes severe mitochondrial morphological defects, loss of mitochondrial nucleic acids, and impaired mitochondrial protein synthesis, thereby underscoring its key role in maintaining mitochondrial homeostasis and effective RNA decay by clearing short RNAs generated during processing and degradation processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed biochemical and structural studies have revealed that REXO2 functions as a specialized dinucleotide and nanoRNA degrading enzyme. It binds small RNA and DNA oligonucleotides with high affinity by interacting with the terminal two nucleotides—through hydrophobic and π–π stacking interactions mediated by key residues—and catalyzes hydrolysis via a two–magnesium ion–dependent mechanism. These findings, supported by kinetic analyses of both bacterial and human homologs, highlight the enzyme’s sequence-independent activity necessary for preventing the accumulation of dinucleotides that could otherwise lead to aberrant transcription initiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental role in RNA metabolism, dysregulation of REXO2 has been linked to human disease. In lower grade gliomas, for instance, upregulation of REXO2—under the transcriptional influence of RUNX1—and its hypomethylation correlate with higher immune infiltration and poorer prognosis. In a separate study, a splicing mutation in REXO2 was found to co-segregate with pheochromocytoma in a familial context, suggesting that loss of proper REXO2 function might contribute to tumorigenesis via effects on DNA repair, replication, and recombination processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francesco Bruni, Pasqua Gramegna, Jorge M A Oliveira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "REXO2 is an oligoribonuclease active in human mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0064670"}], "href": "https://doi.org/10.1371/journal.pone.0064670"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23741365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23741365"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maciej Szewczyk, Deepshikha Malik, Lukasz S Borowski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human REXO2 controls short mitochondrial RNAs generated by mtRNA processing and decay machinery to prevent accumulation of double-stranded RNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkaa302"}], "href": "https://doi.org/10.1093/nar/gkaa302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32365187"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32365187"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Thomas J Nicholls, Henrik Spåhr, Shan Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2019.09.010"}], "href": "https://doi.org/10.1016/j.molcel.2019.09.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31588022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31588022"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lee-Ya Chu, Sashank Agrawal, Yi-Ping Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into nanoRNA degradation by human Rexo2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.070557.119"}], "href": "https://doi.org/10.1261/rna.070557.119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30926754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30926754"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ah Young Park, Christopher M Elvin, Samir M Hamdan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hydrolysis of the 5'-p-nitrophenyl ester of TMP by oligoribonucleases (ORN) from Escherichia coli, Mycobacterium smegmatis, and human."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Expr Purif (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pep.2007.10.005"}], "href": "https://doi.org/10.1016/j.pep.2007.10.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18023590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18023590"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Haiwei Wang, Xinrui Wang, Liangpu Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-91382-1"}], "href": "https://doi.org/10.1038/s41598-021-91382-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34088969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34088969"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yael Laitman, Shay Tzur, Ruben Attai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline variant in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "REXO2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " is a novel candidate gene in familial pheochromocytoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Res (Camb) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0016672320000038"}], "href": "https://doi.org/10.1017/S0016672320000038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32354376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32354376"}]}]}]}
Synonyms	SFN, RFN, REX2, CGI-114
Proteins	ORN_HUMAN
NCBI Gene ID	25996
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

REXO2 has 9,098 functional associations with biological entities spanning 9 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, sequence feature) extracted from 118 datasets.

Click the + buttons to view associations for REXO2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with REXO2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with REXO2 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 REXO2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of REXO2 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 REXO2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing REXO2 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 REXO2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing REXO2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing REXO2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with REXO2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with REXO2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 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 REXO2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at REXO2 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 REXO2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of REXO2 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 REXO2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of REXO2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with REXO2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.