CCNK Gene

HGNC Family	Cyclins (CCN)
Name	cyclin K
Description	The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDK) that phosphorylate the C-terminal domain (CTD) of the large subunit of RNA polymerase II. This gene product may play a dual role in regulating CDK and RNA polymerase II activities. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclin K (CCNK) serves as a pivotal regulatory subunit that partners with transcription‐associated cyclin‐dependent kinases—most notably CDK12 and CDK13—to modulate several critical cellular processes. In metazoans, CCNK forms complexes (with CDK12/CDK13) that phosphorylate the carboxy‐terminal domain (CTD) of RNA polymerase II, thereby facilitating transcription elongation, co‐transcriptional RNA processing, and the proper expression of genes involved in the DNA damage response and homologous recombination."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, these CCNK-containing complexes contribute to maintaining genome stability by ensuring proper assembly of the pre‐replicative complex and by regulating cell cycle progression. In embryonic stem cells, high expression of CCNK (in association with CDK12 and CDK13) is required to sustain self-renewal and pluripotency, whereas its downregulation triggers differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, emerging chemical biology studies have demonstrated that targeted degradation of CCNK—via novel molecular glue compounds—disrupts CDK12 function, impairs CTD phosphorylation, diminishes the expression of DNA repair genes, and sensitizes tumor cells to replication stress. These findings not only illuminate CCNK’s indispensable role in transcriptional regulation and genome integrity but also reveal its potential as a therapeutic target in cancers characterized by genomic instability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, the studies indicate that Cyclin K is a multifaceted regulator—integral to RNA polymerase II–mediated transcription, DNA repair, and cell cycle control—whose dysregulation can contribute to oncogenesis and may be exploited for therapeutic interventions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bartlomiej Bartkowiak, Pengda Liu, Hemali P Phatnani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1968210"}], "href": "https://doi.org/10.1101/gad.1968210"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20952539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20952539"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S-W Grace Cheng, Michael A Kuzyk, Annie Moradian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of cyclin-dependent kinase 12/CrkRS with cyclin K1 is required for the phosphorylation of the C-terminal domain of RNA polymerase II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.06267-11"}], "href": "https://doi.org/10.1128/MCB.06267-11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22988298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22988298"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Qian Dai, Tingjun Lei, Changhong Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells."}]}, {"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.M111.321760"}], "href": "https://doi.org/10.1074/jbc.M111.321760"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22547058"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22547058"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tingjun Lei, Peixuan Zhang, Xudong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin K regulates prereplicative complex assembly to promote mammalian cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-04258-w"}], "href": "https://doi.org/10.1038/s41467-018-04258-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29760377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29760377"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Toshiki Mori, Yoshio Anazawa, Kuniko Matsui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin K as a direct transcriptional target of the p53 tumor suppressor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.neo.7900235"}], "href": "https://doi.org/10.1038/sj.neo.7900235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11988847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11988847"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lu Lv, Peihao Chen, Longzhi Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.59994"}], "href": "https://doi.org/10.7554/eLife.59994"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32804079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32804079"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sebastian M Dieter, Christine Siegl, Paula L Codó, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109394"}], "href": "https://doi.org/10.1016/j.celrep.2021.109394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34289372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34289372"}]}]}]}
Synonyms	CPR4, IDDHDF
Proteins	CCNK_HUMAN
NCBI Gene ID	8812
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CCNK has 6,214 functional associations with biological entities spanning 8 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) extracted from 108 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

CCNK 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 CCNK 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 CCNK 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 CCNK gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CCNK 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 CCNK 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 CCNK 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 CCNK 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 CCNK 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 CCNK 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 CCNK 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 CCNK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CCNK 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 CCNK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CCNK 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 CCNK 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 CCNK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CCNK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CCNK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CCNK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CCNK 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 CCNK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CCNK protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CCNK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CCNK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CCNK gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CCNK 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 CCNK 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 CCNK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CCNK 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 CCNK 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 CCNK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CCNK 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 CCNK 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 CCNK gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CCNK 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 CCNK from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of CCNK 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 CCNK 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 CCNK gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CCNK gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.