DIS3 Gene

HGNC Family	Exosome components (EXOSC)
Name	DIS3 exosome endoribonuclease and 3'-5' exoribonuclease
Description	Enables 3'-5'-RNA exonuclease activity; endonuclease activity; and guanyl-nucleotide exchange factor activity. Involved in CUT catabolic process; RNA processing; and rRNA catabolic process. Located in cytosol and nucleoplasm. Part of nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DIS3 is an evolutionarily conserved ribonucleolytic enzyme that functions as a key catalytic subunit of the RNA exosome complex. In eukaryotic cells, DIS3 exhibits both processive 3′→5′ exonuclease and endonuclease activities that are critical for the processing, surveillance, and degradation of a wide range of RNA substrates – from precursor ribosomal RNAs and other structured noncoding RNAs to aberrant or unwanted RNA degradation intermediates."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In human cells, DIS3 is predominantly nuclear and operates in close association with other exosome catalytic subunits (such as RRP6) to ensure proper maturation, quality control, and steady‐state levels of diverse transcripts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Disruption of DIS3 function, including mutations that impair its enzymatic activity, results in the accumulation of aberrant RNAs and defects in key cellular processes like cell cycle progression and antibody diversification; indeed, such mutations are recurrently observed in multiple myeloma, suggesting a tumor‐suppressor role for DIS3."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Furthermore, studies of DIS3-deficient cells underscore its essential contribution not only to RNA decay but also to the maintenance of genomic integrity and proper nuclear architecture."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these findings reveal that DIS3 plays a pivotal role in regulating RNA metabolism and cellular homeostasis, and that its dysfunction can have profound implications for oncogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rafal Tomecki, Maiken S Kristiansen, Søren Lykke-Andersen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2010.121"}], "href": "https://doi.org/10.1038/emboj.2010.121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20531386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20531386"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "T Shiomi, K Fukushima, N Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human dis3p, which binds to either GTP- or GDP-Ran, complements Saccharomyces cerevisiae dis3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/oxfordjournals.jbchem.a022020"}], "href": "https://doi.org/10.1093/oxfordjournals.jbchem.a022020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9562621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9562621"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Piotr Gerlach, Jan M Schuller, Fabien Bonneau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct and evolutionary conserved structural features of the human nuclear exosome complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.38686"}], "href": "https://doi.org/10.7554/eLife.38686"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30047866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30047866"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sophie R Robinson, Antony W Oliver, Timothy J Chevassut, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The 3' to 5' Exoribonuclease DIS3: From Structure and Mechanisms to Biological Functions and Role in Human Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom5031515"}], "href": "https://doi.org/10.3390/biom5031515"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26193331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26193331"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Susann Weißbach, Christian Langer, Bernhard Puppe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The molecular spectrum and clinical impact of DIS3 mutations in multiple myeloma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Haematol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bjh.13256"}], "href": "https://doi.org/10.1111/bjh.13256"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25521164"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25521164"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marta Lionetti, Marzia Barbieri, Katia Todoerti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A compendium of DIS3 mutations and associated transcriptional signatures in plasma cell dyscrasias."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4674"}], "href": "https://doi.org/10.18632/oncotarget.4674"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26305418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26305418"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lee Davidson, Laura Francis, Ross A Cordiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rapid Depletion of DIS3, EXOSC10, or XRN2 Reveals the Immediate Impact of Exoribonucleolysis on Nuclear RNA Metabolism and Transcriptional Control."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.02.012"}], "href": "https://doi.org/10.1016/j.celrep.2019.02.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30840897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30840897"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Brice Laffleur, Junghyun Lim, Wanwei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Noncoding RNA processing by DIS3 regulates chromosomal architecture and somatic hypermutation in B cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-020-00772-0"}], "href": "https://doi.org/10.1038/s41588-020-00772-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33526923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33526923"}]}]}]}
Synonyms	2810028N01RIK, DIS3P, EXOSC11, RRP44, KIAA1008
Proteins	RRP44_HUMAN
NCBI Gene ID	22894
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DIS3 has 7,082 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 117 datasets.

Click the + buttons to view associations for DIS3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DIS3 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 DIS3 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 DIS3 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 DIS3 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 DIS3 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 DIS3 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 DIS3 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 DIS3 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 DIS3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of DIS3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DIS3 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 DIS3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DIS3 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 DIS3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DIS3 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 DIS3 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 DIS3 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 DIS3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DIS3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DIS3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DIS3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DIS3 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 DIS3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing DIS3 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of DIS3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DIS3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DIS3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DIS3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DIS3 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 DIS3 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 DIS3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DIS3 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 DIS3 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 DIS3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DIS3 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 DIS3 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 DIS3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DIS3 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 DIS3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of DIS3 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 DIS3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.