UPF1 Gene

Name	UPF1 regulator of nonsense transcripts homolog (yeast)
Description	This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located only in the cytoplasm. When translation ends, it interacts with the protein that is a functional homolog of yeast Upf2p to trigger mRNA decapping. Use of multiple polyadenylation sites has been noted for this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUPF1 is a central RNA helicase that orchestrates mRNA quality‐control through the nonsense‐mediated decay (NMD) pathway. In response to premature translation termination, UPF1 is recruited to target mRNAs via interactions with exon–junction complexes and release factors, assembling into a surveillance (SURF) complex that is activated by phosphorylation through SMG1. This phosphorylation enables UPF1 to engage additional NMD factors such as SMG5, SMG7, and protein phosphatases, which promote remodeling and subsequent decay of aberrant transcripts—including specialized targets like replication‐dependent histone mRNAs. Structural and biochemical studies further reveal that UPF1 shifts from a high‐affinity, RNA clamping state to an active unwinding conformation upon binding UPF2, while its ATPase cycle governs selective RNA target discrimination and the efficient disassembly of degrading messenger ribonucleoprotein complexes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in NMD, UPF1 functions as a multifaceted regulator of RNA and genome metabolism. Its robust ATPase and helicase activities enable efficient remodeling and disassembly of ribonucleoprotein complexes, thereby mediating alternative mRNA decay processes such as decapping and glucocorticoid receptor–mediated mRNA turnover. UPF1 also directly interacts with other RNA helicases and processing factors to influence the fate of diverse transcripts and is implicated in non‐RNA‐decay roles that include safeguarding DNA replication, maintaining telomere integrity, and resolving RNA–DNA hybrid (R‐loop) structures at double‐strand breaks. Moreover, deregulated UPF1 activity has been linked to viral pathogenesis, neurodegenerative disorders, and tumorigenesis, reflecting its integration within complex regulatory loops involving noncoding RNAs and partner proteins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joshua T Mendell, Colette M J ap Rhys, Harry C Dietz "}, {"type": "b", "children": [{"type": "t", "text": "Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1074428"}], "href": "https://doi.org/10.1126/science.1074428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12228722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12228722"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jens Lykke-Andersen "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.23.8114-8121.2002"}], "href": "https://doi.org/10.1128/MCB.22.23.8114-8121.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12417715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12417715"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tetsuo Ohnishi, Akio Yamashita, Isao Kashima, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1409612112"}], "href": "https://doi.org/10.1073/pnas.1409612112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25775514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25775514"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Suzanne R Lee, Gabriel A Pratt, Fernando J Martinez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-016-0286-2"}], "href": "https://doi.org/10.1186/s13046-016-0286-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26759305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26759305"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Sébastien Durand, Tobias M Franks, Jens Lykke-Andersen "}, {"type": "b", "children": [{"type": "t", "text": "Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms12434"}], "href": "https://doi.org/10.1038/ncomms12434"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27511142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27511142"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Li Li, Yingying Geng, Ru Feng, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12631"}], "href": "https://doi.org/10.1002/1878-0261.12631"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31919993"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31919993"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Yu Sun, Aziz Eshov, Jeffrey Zhou, et al. 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Synonyms	HUPF1, NORF1, PNORF1, RENT1, SMG-2
Proteins	RENT1_HUMAN
NCBI Gene ID	5976
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UPF1 has 8,393 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 122 datasets.

Click the + buttons to view associations for UPF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UPF1 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 UPF1 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 UPF1 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 UPF1 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 UPF1 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 UPF1 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 UPF1 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 UPF1 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 UPF1 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 UPF1 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 UPF1 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 UPF1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of UPF1 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 UPF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with UPF1 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 UPF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UPF1 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 UPF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with UPF1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing UPF1 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 UPF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UPF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing UPF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing UPF1 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 UPF1 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 UPF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing UPF1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of UPF1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UPF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with UPF1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with UPF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with UPF1 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 UPF1 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 UPF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UPF1 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 UPF1 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 UPF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UPF1 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 UPF1 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 UPF1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UPF1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.