ENOSF1 Gene

Name	enolase superfamily member 1
Description	This gene can encode a mitochondrial enzyme that is thought to convert L-fuconate to 2-keto-3-deoxy-L-fuconate. This locus was originally identified as the source of antisense RNAs of the adjacent thymidylate synthase gene. Splice variants at this locus may contain an alternate 3' exon that is complementary to the 3'UTR and terminal intron of the thymidylate synthase (TS) RNA and may downregulate TS expression. [provided by RefSeq, Aug 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ENOSF1 is a gene that has emerged as an important modulator of thymidylate synthase (TS) activity and, consequently, fluoropyrimidine‐based chemotherapy outcome. In several studies, genetic polymorphisms in ENOSF1 – in particular the intronic variant rs2612091 – have been robustly associated with increased risk of capecitabine toxicity, including severe hand‐foot syndrome, suggesting that the causative effects previously attributed to nearby TYMS variants may actually be mediated through ENOSF1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in mediating drug toxicity, ENOSF1 – also known as the reverse thymidylate synthase (rTS) gene – is transcribed in the antisense orientation relative to TYMS and produces several protein isoforms (rTSα, rTSβ, and a mitochondrial rTSγ) with potential regulatory functions. Experimental evidence indicates that the rTSβ protein participates in a signaling pathway, possibly by generating diffusible lipophilic metabolites from methionine that downregulate TS expression. This observation links ENOSF1 function to the modulation of DNA biosynthesis and, by extension, chemotherapeutic resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, ENOSF1 has been implicated as a potential biomarker in diverse clinical settings. For example, increased expression of ENOSF1 peptides has been detected in the serum of gastric cancer patients, and its genomic variants have been associated with risk in endometrial and thyroid cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": " Furthermore, a prospective clinical study incorporating a DNA‐based test (ToxNav) confirmed that ENOSF1 variants can provide actionable information to help personalize fluoropyrimidine dosing in colorectal cancer patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings support a multifaceted role for ENOSF1 – through both its genetic variation and protein isoforms – in regulating TS expression via antisense mechanisms and in influencing the toxicity and efficacy of chemotherapeutic regimes. Its involvement in metabolic and developmental pathways further suggests that ENOSF1 may participate in broader aspects of cellular differentiation and stress responses.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dan Rosmarin, Claire Palles, Alistair Pagnamenta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gut (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/gutjnl-2013-306571"}], "href": "https://doi.org/10.1136/gutjnl-2013-306571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24647007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24647007"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xandra García-González, Lucía Cortejoso, María I García, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.3289"}], "href": "https://doi.org/10.18632/oncotarget.3289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25691056"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25691056"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Si-Qi Dong, Tong-Min Wang, Jiang-Bo Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res Treat (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4143/crt.2020.457"}], "href": "https://doi.org/10.4143/crt.2020.457"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33285053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33285053"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maarten J Deenen, Didier Meulendijks, Henk Boot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phase 1a/1b and pharmacogenetic study of docetaxel, oxaliplatin and capecitabine in patients with advanced cancer of the stomach or the gastroesophageal junction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Chemother Pharmacol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00280-015-2872-y"}], "href": "https://doi.org/10.1007/s00280-015-2872-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26499900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26499900"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sabyasachi Senapati, Shalini Singh, Mitashree Das, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide analysis of methotrexate pharmacogenomics in rheumatoid arthritis shows multiple novel risk variants and leads for TYMS regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenet Genomics (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FPC.0000000000000036"}], "href": "https://doi.org/10.1097/FPC.0000000000000036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24583629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24583629"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Daniel J Wichelecki, D Sean Froese, Jolanta Kopec, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enzymatic and structural characterization of rTSγ provides insights into the function of rTSβ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi500349e"}], "href": "https://doi.org/10.1021/bi500349e"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24697329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24697329"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ping Liang, Jayakumar R Nair, Lei Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative genomic analysis reveals a novel mitochondrial isoform of human rTS protein and unusual phylogenetic distribution of the rTS gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genomics (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2164-6-125"}], "href": "https://doi.org/10.1186/1471-2164-6-125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16162288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16162288"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wen Shan Yew, Alexander A Fedorov, Elena V Fedorov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evolution of enzymatic activities in the enolase superfamily: L-fuconate dehydratase from Xanthomonas campestris."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi061687o"}], "href": "https://doi.org/10.1021/bi061687o"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17144652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17144652"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xian Guo, Jie Pei, Xuezhi Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative Proteomic Analysis of Yak Follicular Fluid during Estrus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Asian-Australas J Anim Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5713/ajas.15.0724"}], "href": "https://doi.org/10.5713/ajas.15.0724"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26954118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26954118"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Wang-Hong Xu, Ji-Rong Long, Wei Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of thymidylate synthase gene with endometrial cancer risk in a Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Epidemiol Biomarkers Prev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1055-9965.EPI-08-0831"}], "href": "https://doi.org/10.1158/1055-9965.EPI-08-0831"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19190136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19190136"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Monia Zidane, Thérèse Truong, Fabienne Lesueur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of DNA Repair Variants and Diagnostic Radiology Exams in Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Epidemiol Biomarkers Prev (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1055-9965.EPI-20-1142"}], "href": "https://doi.org/10.1158/1055-9965.EPI-20-1142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33827984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33827984"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Lennard Y W Lee, Thomas Starkey, Shivan Sivakumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ToxNav germline genetic testing and PROMinet digital mobile application toxicity monitoring: Results of a prospective single-center clinical utility study-PRECISE study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.2529"}], "href": "https://doi.org/10.1002/cam4.2529"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31486228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31486228"}]}]}]}
Synonyms	HSRTSBETA, TYMSAS, FUCD
Proteins	ENOF1_HUMAN
NCBI Gene ID	55556
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ENOSF1 has 7,530 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 106 datasets.

Click the + buttons to view associations for ENOSF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ENOSF1 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 ENOSF1 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 ENOSF1 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 ENOSF1 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 ENOSF1 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 ENOSF1 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 ENOSF1 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 ENOSF1 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 ENOSF1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ENOSF1 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 ENOSF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ENOSF1 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 ENOSF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ENOSF1 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 ENOSF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ENOSF1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ENOSF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ENOSF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ENOSF1 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 ENOSF1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ENOSF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ENOSF1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ENOSF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ENOSF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for ENOSF1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ENOSF1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ENOSF1 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 ENOSF1 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 ENOSF1 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 ENOSF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ENOSF1 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 ENOSF1 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 ENOSF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ENOSF1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	GAD Gene-Disease Associations	diseases associated with ENOSF1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ENOSF1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ENOSF1 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 ENOSF1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ENOSF1 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 ENOSF1 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 ENOSF1 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.