FEN1 Gene

Name	flap structure-specific endonuclease 1
Description	The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Flap endonuclease 1 (FEN1) is a structure‐specific nuclease that plays a pivotal role in both DNA replication and repair. It removes RNA and DNA 5′ flaps generated during lagging strand synthesis and various repair processes—including long‐patch base excision repair—by precisely recognizing and incising nicked double‐stranded DNA substrates. Structural analyses reveal that FEN1 bends the DNA and employs a helical cap and gateway to channel single‐stranded flaps into a two‐metal ion active site, ensuring cleavage specificity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Furthermore, FEN1 activity is stimulated by its interaction with proliferating cell nuclear antigen (PCNA), which not only enhances its endonuclease function during Okazaki fragment processing but also facilitates its coordination with other repair factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic studies have demonstrated that functional deficiency or haploinsufficiency of FEN1 leads to the accumulation of unprocessed flap structures, resulting in mutations, genomic instability, and a predisposition to cancer, particularly in the gastrointestinal tract when combined with mutations in tumor suppressor genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, posttranscriptional regulation of FEN1—for example, via miR-24, which modulates its expression along with other cell-cycle regulatory genes—further underscores its crucial role in maintaining proper cell proliferation and genomic integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, recent studies have identified FEN1 as a synthetic lethal target in homologous recombination–deficient cancers: the 5′ flap endonuclease activity of FEN1 is essential for the survival of BRCA-deficient cells, suggesting that its inhibition may be exploited therapeutically."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these findings emphasize FEN1’s central role as a guardian of genome stability through its precise nuclease activity in both DNA replication and repair.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Susan E Tsutakawa, Scott Classen, Brian R Chapados, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2011.03.004"}], "href": "https://doi.org/10.1016/j.cell.2011.03.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21496641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21496641"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shigeru Sakurai, Ken Kitano, Hiroto Yamaguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for recruitment of human flap endonuclease 1 to PCNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600519"}], "href": "https://doi.org/10.1038/sj.emboj.7600519"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15616578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15616578"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rajendra Prasad, Yuan Liu, Leesa J Deterding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HMGB1 is a cofactor in mammalian base excision repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.06.029"}], "href": "https://doi.org/10.1016/j.molcel.2007.06.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17803946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17803946"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Melanie Kucherlapati, Kan Yang, Mari Kuraguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Haploinsufficiency of Flap endonuclease (Fen1) leads to rapid tumor progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.152321699"}], "href": "https://doi.org/10.1073/pnas.152321699"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12119409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12119409"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Li Zheng, Huifang Dai, Mian Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fen1 mutations result in autoimmunity, chronic inflammation and cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1599"}], "href": "https://doi.org/10.1038/nm1599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17589521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17589521"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ashish Lal, Francisco Navarro, Christopher A Maher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to \"seedless\" 3'UTR microRNA recognition elements."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2009.08.020"}], "href": "https://doi.org/10.1016/j.molcel.2009.08.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19748357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19748357"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kristen E Mengwasser, Richard O Adeyemi, Yumei Leng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets."}]}, {"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.2018.12.008"}], "href": "https://doi.org/10.1016/j.molcel.2018.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30686591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30686591"}]}]}]}
Synonyms	RAD2, MF1, FEN-1
Proteins	FEN1_HUMAN
NCBI Gene ID	2237
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FEN1 has 15,338 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 128 datasets.

Click the + buttons to view associations for FEN1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FEN1 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 FEN1 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 FEN1 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 FEN1 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 FEN1 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 FEN1 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 FEN1 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 FEN1 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 FEN1 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 FEN1 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 FEN1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of FEN1 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 FEN1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with FEN1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with FEN1 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 FEN1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FEN1 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 FEN1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of FEN1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FEN1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FEN1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing FEN1 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 FEN1 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 FEN1 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 FEN1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing FEN1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FEN1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FEN1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FEN1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with FEN1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of FEN1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with FEN1 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 FEN1 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 FEN1 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 FEN1 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 FEN1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FEN1 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 FEN1 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 FEN1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FEN1 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 FEN1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.