DIS3L2 Gene

Name	DIS3 like 3'-5' exoribonuclease 2
Description	The protein encoded by this gene is similar in sequence to 3'/5' exonucleolytic subunits of the RNA exosome. The exosome is a large multimeric ribonucleotide complex responsible for degrading various RNA substrates. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Mar 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DIS3L2 is a unique, exosome‐independent 3′–5′ exoribonuclease that plays a critical role in RNA quality control by selectively recognizing and degrading oligo‐uridylated substrates. Its well‐characterized function in degrading uridylated precursor let‐7 microRNAs (generated upon LIN28 binding and TUT4/7‐mediated uridylation) enables it to modulate miRNA biogenesis in pluripotent cells, thereby influencing cell fate decisions and tumor suppressor pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition to this key role in miRNA regulation, DIS3L2 contributes to the turnover of a broad spectrum of aberrantly processed or structured noncoding RNAs – including rRNAs, snRNAs, snoRNAs, vault RNAs and others – thus ensuring proper RNA surveillance and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Furthermore, DIS3L2 participates in the decay of specific mRNA substrates—including certain nonsense‐mediated decay targets—thereby impacting cytoplasmic RNA turnover, endoplasmic reticulum–targeted translation and even intracellular calcium homeostasis, events that are essential for proper stem cell differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Notably, genetic inactivation or mutation of DIS3L2 is linked to developmental disorders such as Perlman syndrome and predisposes to Wilms tumor by disrupting cell cycle regulation and mitotic checkpoint control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Emerging evidence also suggests that DIS3L2 influences alternative splicing events and broader miRNA regulatory networks in cancers, including hepatocellular carcinoma, further underscoring its importance in both normal physiology and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": " Finally, altered DIS3L2 function may contribute to neurodegenerative processes through its aberrant sequestration in nuclear inclusions, highlighting the enzyme’s diverse roles in maintaining RNA metabolism and cellular integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dmytro Ustianenko, Dominika Hrossova, David Potesil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.040055.113"}], "href": "https://doi.org/10.1261/rna.040055.113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24141620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24141620"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shuibin Lin, Richard I Gregory "}, {"type": "b", "children": [{"type": "t", "text": "Identification of small molecule inhibitors of Zcchc11 TUTase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2015.1058478"}], "href": "https://doi.org/10.1080/15476286.2015.1058478"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26114892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26114892"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hiroshi I Suzuki, Akihiro Katsura, Kohei Miyazono "}, {"type": "b", "children": [{"type": "t", "text": "A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.12721"}], "href": "https://doi.org/10.1111/cas.12721"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26080928"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26080928"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dmytro Ustianenko, Josef Pasulka, Zuzana Feketova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TUT-DIS3L2 is a mammalian surveillance pathway for aberrant structured non-coding RNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201694857"}], "href": "https://doi.org/10.15252/embj.201694857"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27647875"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27647875"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anna Łabno, Zbigniew Warkocki, Tomasz Kuliński, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Perlman syndrome nuclease DIS3L2 controls cytoplasmic non-coding RNAs and provides surveillance pathway for maturing snRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkw649"}], "href": "https://doi.org/10.1093/nar/gkw649"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27431325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27431325"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mehdi Pirouz, Chih-Hao Wang, Qi Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Perlman syndrome DIS3L2 exoribonuclease safeguards endoplasmic reticulum-targeted mRNA translation and calcium ion homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-16418-y"}], "href": "https://doi.org/10.1038/s41467-020-16418-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32457326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32457326"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Adriana Roithová, Zuzana Feketová, Štěpánka Vaňáčová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DIS3L2 and LSm proteins are involved in the surveillance of Sm ring-deficient snRNAs."}]}, {"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/gkaa301"}], "href": "https://doi.org/10.1093/nar/gkaa301"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32374871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32374871"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Paulo J da Costa, Juliane Menezes, Margarida Saramago, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for DIS3L2 over natural nonsense-mediated mRNA decay targets in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.08.105"}], "href": "https://doi.org/10.1016/j.bbrc.2019.08.105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31466720"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31466720"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Dewi Astuti, Mark R Morris, Wendy N Cooper, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.1071"}], "href": "https://doi.org/10.1038/ng.1071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22306653"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22306653"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Mehdi Pirouz, Peng Du, Marzia Munafò, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dis3l2-Mediated Decay Is a Quality Control Pathway for Noncoding RNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.07.025"}], "href": "https://doi.org/10.1016/j.celrep.2016.07.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27498873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27498873"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Siddharth Shukla, Glen A Bjerke, Denise Muhlrad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RNase PARN Controls the Levels of Specific miRNAs that Contribute to p53 Regulation."}]}, {"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.2019.01.010"}], "href": "https://doi.org/10.1016/j.molcel.2019.01.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30770239"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30770239"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Acong Yang, Tie-Juan Shao, Xavier Bofill-De Ros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-16533-w"}], "href": "https://doi.org/10.1038/s41467-020-16533-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32488030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32488030"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jakub Stanislaw Nowak, Fruzsina Hobor, Angela Downie Ruiz Velasco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.059196.116"}], "href": "https://doi.org/10.1261/rna.059196.116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27881476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27881476"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Fumiaki Mori, Kunikazu Tanji, Yasuo Miki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunohistochemical localization of exoribonucleases (DIS3L2 and XRN1) in intranuclear inclusion body disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2017.10.061"}], "href": "https://doi.org/10.1016/j.neulet.2017.10.061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29100804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29100804"}]}]}]}
Synonyms	FAM6A, HDIS3L2, PRLMNS
Proteins	DI3L2_HUMAN
NCBI Gene ID	129563
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DIS3L2 has 5,116 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 112 datasets.

Click the + buttons to view associations for DIS3L2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DIS3L2 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 DIS3L2 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 DIS3L2 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 DIS3L2 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 DIS3L2 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 DIS3L2 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 DIS3L2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DIS3L2 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 DIS3L2 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 DIS3L2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DIS3L2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DIS3L2 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 DIS3L2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DIS3L2 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 DIS3L2 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 DIS3L2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with DIS3L2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DIS3L2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DIS3L2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DIS3L2 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 DIS3L2 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 DIS3L2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DIS3L2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with DIS3L2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with DIS3L2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DIS3L2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with DIS3L2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DIS3L2 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 DIS3L2 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 DIS3L2 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 DIS3L2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DIS3L2 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 DIS3L2 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 DIS3L2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DIS3L2 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 DIS3L2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DIS3L2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DIS3L2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of DIS3L2 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 DIS3L2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of DIS3L2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.