CDK2AP1 Gene

Name	cyclin-dependent kinase 2 associated protein 1
Description	The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. This protein was found to also interact with DNA polymerase alpha/primase and mediate the phosphorylation of the large p180 subunit, which suggests a regulatory role in DNA replication during the S-phase of the cell cycle. This protein also forms a core subunit of the nucleosome remodeling and histone deacetylation (NURD) complex that epigenetically regulates embryonic stem cell differentiation. This gene thus plays a role in both cell-cycle and epigenetic regulation. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclin‐dependent kinase 2–associated protein 1 (CDK2AP1) is emerging as a multifunctional regulator that integrates cell cycle control with epigenetic modulation and differentiation. At its core, CDK2AP1 acts as a specific inhibitor of CDK2 activity during the G1–to–S phase transition, thereby enforcing cell cycle checkpoints and suppressing unchecked proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In embryonic stem cells, CDK2AP1 plays a pivotal role in establishing differentiation competency by promoting epigenetic silencing of pluripotency genes such as Oct4. This is achieved through physical interaction with the methyl DNA–binding protein MBD3 and recruitment of components of the NuRD chromatin remodeling complex, which in turn modulates pathways including Wnt signaling and retinoblastoma protein (pRb) phosphorylation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In several cancer models, downregulation of CDK2AP1—often mediated by microRNA‐21—results in reduced inhibition of CDK2, leading to increased proliferation, invasion, and tumorigenesis. Such aberrant expression is associated with enhanced malignant phenotypes in oral, prostate, glioma, and myxofibrosarcoma cells, where restoration of CDK2AP1 expression induces G0/G1 arrest and promotes apoptotic pathways via the mitochondrial cascade or through p53‐dependent mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, reduced CDK2AP1 expression—either through microRNA regulation or via genetic variants—is linked not only to deregulated cell cycle progression and impaired differentiation but also to altered TGF-β/Smad signaling, which compromises growth inhibition in cancers such as oral squamous cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In addition, CDK2AP1 assists the NuRD complex in engaging specific promoters (for instance, those of Wnt signaling genes) in pluripotent cells, further underscoring its role in epigenetic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, studies in primary human fibroblasts have demonstrated that loss of CDK2AP1 leads to p53 stabilization, cell cycle perturbations, and premature senescence, emphasizing its importance in maintaining normal cell cycle dynamics and genomic integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these findings highlight CDK2AP1’s central role as a cell cycle inhibitor, epigenetic modulator, and tumor suppressor whose dysregulation can contribute to oncogenesis and aberrant differentiation, making it a promising target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Asli Ertekin, James M Aramini, Paolo Rossi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) is dimeric in its disulfide-reduced state, with natively disordered N-terminal region."}]}, {"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.M112.343863"}], "href": "https://doi.org/10.1074/jbc.M112.343863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22427660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22427660"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Amit M Deshpande, Yan-Shan Dai, Yong Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cdk2ap1 is required for epigenetic silencing of Oct4 during murine embryonic stem cell differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C800158200"}], "href": "https://doi.org/10.1074/jbc.C800158200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19117947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19117947"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jeffrey J Kim, Omar Khalid, Sheynie Vo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel regulatory factor recruits the nucleosome remodeling complex to wingless integrated (Wnt) signaling gene promoters in mouse 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.M112.416545"}], "href": "https://doi.org/10.1074/jbc.M112.416545"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23074223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23074223"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yong Kim, Amit Deshpande, Yanshan Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin-dependent kinase 2-associating protein 1 commits murine embryonic stem cell differentiation through retinoblastoma protein regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.026088"}], "href": "https://doi.org/10.1074/jbc.M109.026088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19564334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19564334"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Khaled N Alsayegh, Steven D Sheridan, Shilpa Iyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of CDK2AP1 in human embryonic stem cells reduces the threshold of differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0196817"}], "href": "https://doi.org/10.1371/journal.pone.0196817"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29734353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29734353"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jun Zheng, Hui Xue, Tao Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-21 downregulates the tumor suppressor P12 CDK2AP1 and stimulates cell proliferation and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.22995"}], "href": "https://doi.org/10.1002/jcb.22995"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21328460"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21328460"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Marta B Afonso, Pedro M Rodrigues, André L Simão, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miRNA-21 ablation protects against liver injury and necroptosis in cholestasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-017-0019-x"}], "href": "https://doi.org/10.1038/s41418-017-0019-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29229992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29229992"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Olga Zolochevska, Marxa L Figueiredo "}, {"type": "b", "children": [{"type": "t", "text": "Cell cycle regulator cdk2ap1 inhibits prostate cancer cell growth and modifies androgen-responsive pathway function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.21007"}], "href": "https://doi.org/10.1002/pros.21007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19585490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19585490"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chien-Feng Li, Hsuan-Ying Huang, Wen-Ren Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical aggressiveness of myxofibrosarcomas associates with down-regulation of p12CDK2AP1: prognostic implication of a putative tumor suppressor that induces cell cycle arrest and apoptosis via mitochondrial pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Surg Oncol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1245/s10434-014-3825-0"}], "href": "https://doi.org/10.1245/s10434-014-3825-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24889487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24889487"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yonggang Xu, Jie Wang, Songbin Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of CDK2AP1 by RNA interference inhibits cell growth and tumorigenesis of human glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurol Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1179/1743132813Y.0000000298"}], "href": "https://doi.org/10.1179/1743132813Y.0000000298"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24620959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24620959"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hui Peng, Satoru Shintani, Yong Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of p12CDK2-AP1 expression in human oral squamous cell carcinoma with disrupted transforming growth factor-beta-Smad signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1593/neo.06580"}], "href": "https://doi.org/10.1593/neo.06580"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17217620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17217620"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ritika Gera, Leon Mokbel, Wen G Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mRNA Expression of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "CDK2AP1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " in Human Breast Cancer: Correlation with Clinical and Pathological Parameters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Genomics Proteomics (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/cgp.20103"}], "href": "https://doi.org/10.21873/cgp.20103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30343278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30343278"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Khaled N Alsayegh, Venkat S Gadepalli, Shilpa Iyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of CDK2AP1 in primary human fibroblasts induces p53 dependent senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0120782"}], "href": "https://doi.org/10.1371/journal.pone.0120782"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25785833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25785833"}]}]}]}
Synonyms	DOC1, DORC1, doc-1, ST19, P12DOC-1
Proteins	CDKA1_HUMAN
NCBI Gene ID	8099
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CDK2AP1 has 7,589 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 114 datasets.

Click the + buttons to view associations for CDK2AP1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CDK2AP1 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 CDK2AP1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CDK2AP1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CDK2AP1 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 CDK2AP1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CDK2AP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CDK2AP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CDK2AP1 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 CDK2AP1 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 CDK2AP1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CDK2AP1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CDK2AP1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CDK2AP1 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 CDK2AP1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CDK2AP1 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 CDK2AP1 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 CDK2AP1 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 CDK2AP1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CDK2AP1 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 CDK2AP1 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 CDK2AP1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CDK2AP1 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 CDK2AP1 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 CDK2AP1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CDK2AP1 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 CDK2AP1 from the GeneSigDB Published Gene Signatures dataset.