RFK Gene

Name	riboflavin kinase
Description	Riboflavin kinase (RFK; EC 2.7.1.26) is an essential enzyme that catalyzes the phosphorylation of riboflavin (vitamin B2) to form flavin mononucleotide (FMN), an obligatory step in vitamin B2 utilization and flavin cofactor synthesis (Karthikeyan et al., 2003 [PubMed 12623014]).[supplied by OMIM, Nov 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRiboflavin kinase (RFK) is a pivotal enzyme in flavin metabolism that catalyzes the phosphorylation of riboflavin (vitamin B₂) to produce flavin mononucleotide (FMN), which can then be converted into flavin adenine dinucleotide (FAD). Structural studies on human RFK have revealed unique features in its nucleotide binding and conformational changes upon flavin binding, underscoring an ordered kinetic mechanism that ensures efficient cofactor production. This fundamental role in generating FAD is critical not only for numerous metabolic pathways but also for the activity of flavoproteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nIn addition to its essential catalytic function, RFK has been identified as a key adaptor that physically couples cell surface receptors to the NADPH oxidase complex. Specifically, RFK binds to the TNF receptor 1 (TNFR1) and to p22(phox), facilitating the assembly and activation of NADPH oxidase in response to tumor necrosis factor (TNF) signaling. This bridging function is necessary for TNF-induced reactive oxygen species (ROS) production, highlighting an unexpected role for RFK in immune signaling and inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n\nMoreover, RFK contributes to cellular defense mechanisms against oxidative stress. In prostate cancer cells, overexpression of RFK leads to increased levels of FMN, FAD, and total glutathione, as well as up-regulation of antioxidant enzymes like glutathione reductase and GSTπ. This elevated antioxidant capacity not only protects cells from oxidant-induced damage but also confers resistance to chemotherapeutic agents such as cisplatin, implicating RFK in the malignant progression and drug resistance of certain cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n\nRFK’s bridging capabilities extend further to death receptor-mediated signaling. In tumor cells, RFK is recruited into complexes formed by DR4 and DR5 following stimulation by specific agonists, where it plays an indispensable role in linking these receptors with Nox1 NADPH oxidase. The ensuing ROS production triggers sustained c-Jun N-terminal kinase (JNK) activation and apoptotic cell death, thereby positioning RFK as a critical mediator of ROS-dependent apoptosis in response to death receptor activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Subramanian Karthikeyan, Qingxian Zhou, Andrei L Osterman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi035450t"}], "href": "https://doi.org/10.1021/bi035450t"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14580199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14580199"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Benjamin Yazdanpanah, Katja Wiegmann, Vladimir Tchikov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Riboflavin kinase couples TNF receptor 1 to NADPH oxidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature08206"}], "href": "https://doi.org/10.1038/nature08206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19641494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19641494"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Gen Hirano, Hiroto Izumi, Yoshihiro Yasuniwa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2011.938"}], "href": "https://doi.org/10.3892/ijo.2011.938"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21308351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21308351"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kyung-Jin Park, Chang-Han Lee, Aeyung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Death receptors 4 and 5 activate Nox1 NADPH oxidase through riboflavin kinase to induce reactive oxygen species-mediated apoptotic cell death."}]}, {"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.M111.309021"}], "href": "https://doi.org/10.1074/jbc.M111.309021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22158615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22158615"}]}]}]}
Synonyms	RIFK
Proteins	RIFK_HUMAN
NCBI Gene ID	55312
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RFK has 6,659 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 128 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

RFK 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 RFK 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 RFK 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 RFK 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 RFK 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 RFK 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 RFK 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 RFK 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 RFK 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 RFK 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 RFK gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RFK 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 RFK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RFK protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RFK 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 RFK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RFK 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 RFK 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 RFK gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RFK 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 RFK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RFK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing RFK 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 RFK 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 RFK 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 RFK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RFK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RFK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RFK gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RFK protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DGIdb Drug Targets 2026	interacting drugs for RFK protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RFK 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 RFK 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 RFK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DrugBank Drug Targets	interacting drugs for RFK protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at RFK 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 RFK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RFK 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 RFK from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RFK 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 RFK gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.