CDK2 Gene

HGNC Family	Cyclin-dependent kinases (CDK)
Name	cyclin-dependent kinase 2
Description	This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclin‐dependent kinase 2 (CDK2) is a multifaceted regulator of cell cycle progression that operates primarily at the G1/S transition and during DNA replication, yet its roles vary with cell type and context. In somatic cells, although deletion of CDK2 does not abrogate proliferation because of compensatory mechanisms—most notably the ability of CDK1 to drive cell division—CDK2 remains essential for precise regulation of the cell cycle and is indispensable for proper progression through prophase I during meiosis in germ cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Regulation of CDK2 activity occurs via its association with cyclins (most notably cyclin E) and is tightly controlled by CDK inhibitors such as p21 and p27. For example, the circular RNA circ‐Foxo3 sequesters CDK2 together with p21 in a ternary complex, thereby impeding CDK2 function and arresting cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, upstream signaling pathways modulate CDK2 indirectly; Akt‐mediated phosphorylation reduces the nuclear abundance of the inhibitor p27, thereby relieving inhibition of CDK2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n CDK2 also collaborates with other kinases and cell cycle regulators. It cooperates with proteins such as Plk4, CP110, and Hs‐SAS6 to ensure faithful centrosome duplication during the cell cycle."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In skeletal muscle satellite cells, myostatin down‐regulates CDK2 levels and kinase activity, reinforcing quiescence and limiting the G1/S transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, CDK2 plays a critical role in promoting replication initiation. Aberrant activation of CDK2 under conditions of checkpoint inhibition leads to increased replication initiation, contributing to replication stress and DNA damage if not properly controlled."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " CDK2–cyclin E complexes also participate in coupling cell cycle progression to transcriptional events; for instance, they phosphorylate components of the histone transcription machinery, thereby linking histone gene expression to DNA replication."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, CDK2 directly phosphorylates substrates such as Smad3, modulating its transcriptional activity and thereby impacting TGF‐β–mediated cell cycle arrest mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " However, in several cancer models, inhibition or ablation of CDK2 does not necessarily curb cell proliferation, suggesting a degree of redundancy that limits its suitability as a singular therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In this context, CDK2 activity further facilitates the degradation of the CDK inhibitor p21 through phosphorylation and subsequent recognition by the SCF<sup>Skp2</sup> ubiquitin ligase complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies underscore that CDK2 is a central, highly regulated kinase that integrates diverse upstream signals to coordinate DNA replication, centrosome duplication, and the precise control of cell cycle transitions. Its regulation by RNA molecules, CDK inhibitors, and post‐translational modifications reflects its pivotal role in maintaining proper cell division in both normal development and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David Santamaría, Cédric Barrière, Antonio Cerqueira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cdk1 is sufficient to drive the mammalian cell cycle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06046"}], "href": "https://doi.org/10.1038/nature06046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17700700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17700700"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sagrario Ortega, Ignacio Prieto, Junko Odajima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1232"}], "href": "https://doi.org/10.1038/ng1232"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12923533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12923533"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "William W Du, Weining Yang, Elizabeth Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkw027"}], "href": "https://doi.org/10.1093/nar/gkw027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26861625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26861625"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Incheol Shin, F Michael Yakes, Federico Rojo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm759"}], "href": "https://doi.org/10.1038/nm759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12244301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12244301"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ying Li, Donald Dowbenko, Laurence A Lasky "}, {"type": "b", "children": [{"type": "t", "text": "AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109062200"}], "href": "https://doi.org/10.1074/jbc.M109062200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11756412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11756412"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Robert Habedanck, York-Dieter Stierhof, Christopher J Wilkinson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Polo kinase Plk4 functions in centriole duplication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1320"}], "href": "https://doi.org/10.1038/ncb1320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16244668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16244668"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Seumas McCroskery, Mark Thomas, Linda Maxwell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myostatin negatively regulates satellite cell activation and self-renewal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200207056"}], "href": "https://doi.org/10.1083/jcb.200207056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12963705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12963705"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Randi G Syljuåsen, Claus Storgaard Sørensen, Lasse Tengbjerg Hansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.9.3553-3562.2005"}], "href": "https://doi.org/10.1128/MCB.25.9.3553-3562.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15831461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15831461"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Lei Zheng, Robert G Roeder, Yan Luo "}, {"type": "b", "children": [{"type": "t", "text": "S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(03)00552-x"}], "href": "https://doi.org/10.1016/s0092-8674(03"}, {"type": "t", "text": "00552-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12887926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12887926"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Isao Matsuura, Natalia G Denissova, Guannan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin-dependent kinases regulate the antiproliferative function of Smads."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature02650"}], "href": "https://doi.org/10.1038/nature02650"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15241418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15241418"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Osamu Tetsu, Frank McCormick "}, {"type": "b", "children": [{"type": "t", "text": "Proliferation of cancer cells despite CDK2 inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1535-6108(03)00053-9"}], "href": "https://doi.org/10.1016/s1535-6108(03"}, {"type": "t", "text": "00053-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12676582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12676582"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Gil Bornstein, Joanna Bloom, Danielle Sitry-Shevah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301774200"}], "href": "https://doi.org/10.1074/jbc.M301774200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12730199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12730199"}]}]}]}
Synonyms	CDKN2, P33(CDK2)
Proteins	CDK2_HUMAN
NCBI Gene ID	1017
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CDK2 has 16,777 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 143 datasets.

Click the + buttons to view associations for CDK2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CDK2 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 CDK2 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 CDK2 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 CDK2 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 CDK2 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 CDK2 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 CDK2 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 CDK2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CDK2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CDK2 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 CDK2 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 CDK2 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 CDK2 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 CDK2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CDK2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CDK2 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 CDK2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CDK2 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 CDK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CDK2 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 CDK2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CDK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CDK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CDK2 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 CDK2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CDK2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CDK2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CDK2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CDK2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CDK2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CDK2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate CDK2 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CDK2 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 CDK2 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 CDK2 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 CDK2 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 CDK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CDK2 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 CDK2 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 CDK2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CDK2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.