PFKFB3 Gene

Name	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3
Description	The protein encoded by this gene belongs to a family of bifunctional proteins that are involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate (F2,6BP), and a fructose-2,6-biphosphatase activity that catalyzes the degradation of F2,6BP. This protein is required for cell cycle progression and prevention of apoptosis. It functions as a regulator of cyclin-dependent kinase 1, linking glucose metabolism to cell proliferation and survival in tumor cells. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPFKFB3 is a master regulator of glycolysis whose activity is central to the modulation of energy metabolism in endothelial cells. Its up‐regulation drives increased production of fructose‐2,6‐bisphosphate, which in turn augments glycolytic flux necessary for endothelial cell migration, filopodia and lamellipodia formation, and vessel sprouting. In angiogenic settings, enhanced PFKFB3 activity is critical not only for endothelial proliferation but also for switching cellular metabolism to glycolysis under low‐oxygen or stress‐induced conditions, thereby favoring vascular branching and neovascularization. Such metabolic control has been demonstrated in both in vitro models and animal studies where overexpression of PFKFB3 overcame pro–stalk activity signals, while its inhibition suppressed vessel outgrowth and pathological hyperbranching. (See."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a broad spectrum of malignancies, PFKFB3 not only sustains a high glycolytic rate—the hallmark of the Warburg effect—but also plays unexpected roles in controlling cell proliferation, cell‐cycle progression, and DNA repair. PFKFB3’s nuclear localization and its ability to generate fructose‐2,6‐bisphosphate have been linked to accelerated expression of key cell cycle regulators and activation of cyclin–dependent kinases. Moreover, post‐translational modifications of PFKFB3 (including phosphorylation and methylation) have been shown to contribute to tumor cell survival during prolonged mitotic arrest and to coordinate metabolic switches that support homologous recombination in response to DNA damage. Collectively, these multifaceted functions underline its importance as a driver of oncogenic growth, metastatic stem cell renewal, and a mediator of resistance to conventional therapies. (See."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "17"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPFKFB3 also emerges as a pivotal player in non‐malignant as well as inflammation‐associated contexts. In autoimmune disorders such as rheumatoid arthritis, insufficient induction of PFKFB3 in T cells compromises glycolytic capacity, leading to energy deprivation and enhanced apoptosis. Its transcription is strongly regulated by hypoxic conditions through HIF‐1 binding to promoter elements, a mechanism that is also operative in fibrogenic processes and in the regulation of pancreatic beta cell function. Furthermore, in immune cells like neutrophils and endothelial cells, PFKFB3–dependent glycolysis supports proinflammatory responses and modulates NADPH oxidase activity, thereby linking metabolic reprogramming to innate immune functions. (See."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "23"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katrien De Bock, Maria Georgiadou, Sandra Schoors, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Endothelial PFKFB3 plays a critical role in angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.113.303041"}], "href": "https://doi.org/10.1161/ATVBAHA.113.303041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24700124"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24700124"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anuradha Doddaballapur, Katharina M Michalik, Yosif Manavski, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PFKFB3 gene silencing decreases glycolysis, induces cell-cycle delay and inhibits anchorage-independent growth in HeLa cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2006.04.093"}], "href": "https://doi.org/10.1016/j.febslet.2006.04.093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16698023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16698023"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Shengchen Lin, Yunzhan Li, Dezhen Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fascin promotes lung cancer growth and metastasis by enhancing glycolysis and PFKFB3 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2021.07.025"}], "href": "https://doi.org/10.1016/j.canlet.2021.07.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34303764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34303764"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Siyuan Yan, Nan Zhou, Deru Zhang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "6-Phosphofructo-2-kinase (pfkfb3) gene promoter contains hypoxia-inducible factor-1 binding sites necessary for transactivation in response to hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406096200"}], "href": "https://doi.org/10.1074/jbc.M406096200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15466858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15466858"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Marc Mejias, Javier Gallego, Salvador Naranjo-Suarez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Unexpected function of the phagocyte NADPH oxidase in supporting hyperglycolysis in stimulated neutrophils: key role of 6-phosphofructo-2-kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201600720R"}], "href": "https://doi.org/10.1096/fj.201600720R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27799347"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27799347"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Ruyuan Zhang, Ranran Li, Yiyun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Glycolytic Enzyme PFKFB3 Controls TNF-α-Induced Endothelial Proinflammatory Responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflammation (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10753-018-0880-x"}], "href": "https://doi.org/10.1007/s10753-018-0880-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30171427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30171427"}]}]}]}
Synonyms	iPFK-2, IPFK2, PFK2
Proteins	F263_HUMAN
NCBI Gene ID	5209
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PFKFB3 has 11,759 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 133 datasets.

Click the + buttons to view associations for PFKFB3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PFKFB3 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 PFKFB3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PFKFB3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PFKFB3 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 PFKFB3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PFKFB3 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 PFKFB3 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 PFKFB3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PFKFB3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PFKFB3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PFKFB3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PFKFB3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PFKFB3 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 PFKFB3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 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 PFKFB3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PFKFB3 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 PFKFB3 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 PFKFB3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PFKFB3 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 PFKFB3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.