CHFR Gene

HGNC Family	Zinc fingers
Name	checkpoint with forkhead and ring finger domains, E3 ubiquitin protein ligase
Description	This gene encodes an E3 ubiquitin-protein ligase required for the maintenance of the antephase checkpoint that regulates cell cycle entry into mitosis and, therefore, may play a key role in cell cycle progression and tumorigenesis. The encoded protein has an N-terminal forkhead-associated domain, a central RING-finger domain, and a cysteine-rich C-terminal region. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Mar 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CHFR is a multifunctional checkpoint protein that plays a critical role in delaying progression into mitosis under conditions of mitotic stress. As an E3 ubiquitin ligase containing both forkhead‐associated (FHA) and RING finger domains, CHFR mediates the ubiquitination of key cell cycle regulators – including Polo‐like kinase 1 (Plk1), Aurora A, and histone deacetylase 1 (HDAC1) – thereby preventing premature mitotic entry and maintaining chromosomal stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n In addition, CHFR interacts with poly(ADP‐ribose)–modified proteins such as PARP‑1, stimulating its ubiquitination and degradation, a mechanism that further reinforces a mitotic delay in response to cellular stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Epigenetic inactivation of CHFR via promoter hypermethylation has been frequently observed in a variety of human cancers—including colorectal and esophageal carcinomas—and is associated with a loss of mitotic checkpoint control. Loss of CHFR function has been linked to chromosomal instability, increased sensitivity to microtubule inhibitors, and tumor progression. Moreover, studies in knockout mouse models have supported its tumor-suppressive role by demonstrating deregulation of mitotic kinases such as Aurora A when CHFR is absent."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n Furthermore, CHFR has been shown to work in concert with other ubiquitin ligases (e.g. RNF8) to regulate histone modifications and to modulate the DNA damage response"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ",\n while its ability to catalyze noncanonical Lys63-linked polyubiquitin chains suggests an important role in stress signaling beyond proteasomal degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its checkpoint functions, CHFR also influences cell behavior by downregulating HDAC1, which leads to the upregulation of cell cycle inhibitors and metastasis suppressors—further supporting its candidacy as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n Collectively, these studies indicate that CHFR serves as a critical regulator of mitotic fidelity and genomic stability, with its inactivation via epigenetic silencing contributing to tumorigenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ivan Ahel, Dragana Ahel, Takahiro Matsusaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06420"}], "href": "https://doi.org/10.1038/nature06420"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18172500"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18172500"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dongmin Kang, James Chen, Jim Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200108016"}], "href": "https://doi.org/10.1083/jcb.200108016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11807090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11807090"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "John Bothos, Matthew K Summers, Monica Venere, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1206831"}], "href": "https://doi.org/10.1038/sj.onc.1206831"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14562038"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14562038"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Priya Chaturvedi, Valery Sudakin, Matthew L Bobiak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chfr regulates a mitotic stress pathway through its RING-finger domain with ubiquitin ligase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11912157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11912157"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lisa Kashima, Masashi Idogawa, Hiroaki Mita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHFR protein regulates mitotic checkpoint by targeting PARP-1 protein for ubiquitination and degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.321828"}], "href": "https://doi.org/10.1074/jbc.M111.321828"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22337872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22337872"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shuji Ogino, Katsuhiko Nosho, Gregory J Kirkner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gut (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/gut.2008.155473"}], "href": "https://doi.org/10.1136/gut.2008.155473"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18832519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18832519"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Paul G Corn, Matthew K Summers, Franz Fogt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent hypermethylation of the 5' CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/24.1.47"}], "href": "https://doi.org/10.1093/carcin/24.1.47"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12538348"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12538348"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xiaochun Yu, Katherine Minter-Dykhouse, Liviu Malureanu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chfr is required for tumor suppression and Aurora A regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1538"}], "href": "https://doi.org/10.1038/ng1538"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15793587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15793587"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yasuyuki Shibata, Nobuhiro Haruki, Yoshiyuki Kuwabara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chfr expression is downregulated by CpG island hypermethylation in esophageal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/23.10.1695"}], "href": "https://doi.org/10.1093/carcin/23.10.1695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12376479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12376479"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Johann C Brandes, Manon van Engeland, Kim A D Wouters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHFR promoter hypermethylation in colon cancer correlates with the microsatellite instability phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgi058"}], "href": "https://doi.org/10.1093/carcin/bgi058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15760919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15760919"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jiaxue Wu, Yibin Chen, Lin-Yu Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chfr and RNF8 synergistically regulate ATM activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.2078"}], "href": "https://doi.org/10.1038/nsmb.2078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21706008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21706008"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Young Mi Oh, Young Eun Kwon, Joo Mi Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chfr is linked to tumour metastasis through the downregulation of HDAC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1837"}], "href": "https://doi.org/10.1038/ncb1837"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19182791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19182791"}]}]}]}
Synonyms	RNF116, RNF196
Proteins	CHFR_HUMAN
NCBI Gene ID	55743
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CHFR has 5,634 functional associations with biological entities spanning 9 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, sequence feature) extracted from 113 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

CHFR 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 CHFR 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 CHFR 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 CHFR gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CHFR 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 CHFR 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 CHFR 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 CHFR 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 CHFR 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 CHFR 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 CHFR 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 CHFR gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CHFR 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 CHFR gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CHFR 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 CHFR 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 CHFR gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CHFR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CHFR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CHFR 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 CHFR 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 CHFR gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CHFR gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CHFR gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CHFR gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CHFR 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 CHFR 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 CHFR 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 CHFR 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 CHFR gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CHFR 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 CHFR 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 CHFR gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CHFR 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 CHFR from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CHFR gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CHFR gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CHFR gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CHFR 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 CHFR from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of CHFR gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.