TKFC Gene

Name	triokinase/FMN cyclase
Description	This gene is a member of the family of dihydroxyacetone kinases, which have a protein structure distinct from other kinases. The product of this gene phosphorylates dihydroxyacetone, and also catalyzes the formation of riboflavin 4',5'-phosphate (aka cyclin FMN) from FAD. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTKFC encodes a bifunctional enzyme that plays two key roles in cellular metabolism. On one hand, it functions as a glyceraldehyde kinase that phosphorylates dihydroxyacetone and fructose‐derived glyceraldehyde, a critical step in fructose metabolism. On the other hand, TKFC also exhibits FMN cyclase (FAD-AMP lyase) activity, converting FAD into riboflavin 4′,5′-cyclic phosphate. Structural and kinetic studies have delineated that these activities reside in distinct but interdependent domains within the enzyme, such that binding of substrates for one reaction can inhibit the other. These findings were initially supported by studies on the rat enzyme and further detailed by extensive enzymatic and molecular analyses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its metabolic functions, TKFC—historically referred to in some studies as DAK—has been implicated in the modulation of innate antiviral immunity. Experimental evidence indicates that overexpression of this protein suppresses the MDA5-mediated interferon-β promoter activation, thereby dampening antiviral responses. Conversely, downregulation or genetic deficiency of TKFC leads to enhanced MDA5 signaling. In a clinical context, inborn errors of TKFC function have been associated with developmental delays, cataracts, liver dysfunction, and even fatal cardiomyopathy following viral illnesses, suggesting that disruption of TKFC’s dual roles adversely affects both metabolic homeostasis and the innate immune response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the human TKFC gene displays alternative splicing events that yield distinct transcript variants with tissue-specific expression profiles. While canonical transcripts spanning exons 2 to 18 encode the active, bifunctional enzyme, alternative splicing at intron 17 can generate a shorter variant that lacks enzymatic activity. This differential splicing likely contributes to the regulation of TKFC functions—both in fructose metabolism and in immune modulation—across diverse tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alicia Cabezas, María Jesús Costas, Rosa María Pinto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-dependent dihydroxyacetone kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.10.142"}], "href": "https://doi.org/10.1016/j.bbrc.2005.10.142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16289032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16289032"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joaquim Rui Rodrigues, Ana Couto, Alicia Cabezas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bifunctional homodimeric triokinase/FMN cyclase: contribution of protein domains to the activities of the human enzyme and molecular dynamics simulation of domain movements."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.525626"}], "href": "https://doi.org/10.1074/jbc.M113.525626"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24569995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24569995"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Feici Diao, Shu Li, Yang Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0700544104"}], "href": "https://doi.org/10.1073/pnas.0700544104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17600090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17600090"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Saskia B Wortmann, Brigitte Meunier, Lamia Mestek-Boukhibar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic Variants in TKFC Encoding Triokinase/FMN Cyclase Are Associated with Cataracts and Multisystem Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2020.01.005"}], "href": "https://doi.org/10.1016/j.ajhg.2020.01.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32004446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32004446"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "María Jesús Costas, Ana Couto, Alicia Cabezas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative Splicing of the Last TKFC Intron Yields Transcripts Differentially Expressed in Human Tissues That Code In Vitro for a Protein Devoid of Triokinase and FMN Cyclase Activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom14101288"}], "href": "https://doi.org/10.3390/biom14101288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39456221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39456221"}]}]}]}
Synonyms	DAK, NET45
Proteins	DHAK_HUMAN
NCBI Gene ID	26007
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TKFC has 6,496 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 117 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

TKFC 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 TKFC 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 TKFC 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 TKFC 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 TKFC 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 TKFC 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 TKFC 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 TKFC 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 TKFC 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 TKFC 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 TKFC 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 TKFC gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TKFC protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TKFC 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 TKFC gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TKFC 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 TKFC 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 TKFC gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing TKFC 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 TKFC gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TKFC protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TKFC protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TKFC 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 TKFC protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TKFC gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TKFC gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TKFC protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TKFC gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving TKFC gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TKFC 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 TKFC 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 TKFC gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TKFC 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 TKFC 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 TKFC gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TKFC 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 TKFC 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 TKFC gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TKFC 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 TKFC from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of TKFC gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.