CDKN1A Gene

Name	cyclin-dependent kinase inhibitor 1A (p21, Cip1)
Description	This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CDKN1A, which encodes the cyclin‐dependent kinase inhibitor p21, functions as a pivotal mediator that integrates diverse stress signals to enforce cell cycle arrest, promote differentiation, and stabilize cellular senescence. In response to DNA damage or oncogenic stress, p53‐dependent transcriptional induction of CDKN1A leads to inhibition of cyclin–CDK complexes (e.g. CDK2), thereby halting cell cycle progression at the G1/S checkpoint and facilitating terminal differentiation in tissues such as the intestinal epithelium (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, p21 participates in noncanonical regulatory complexes – for instance, interaction with cyclin–dependent kinase 2 and circRNAs contributes to cell cycle arrest by forming inhibitory ternary complexes (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " p21 expression is also modulated by extracellular and intracellular cues; cell surface molecules such as CD44 variants can influence its expression to affect tumor growth (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and transcription factors including FoxO and HIF‐1α overcome c‐Myc–mediated repression to derepress p21, thereby initiating growth‐inhibitory programs (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, microRNAs—such as members of the miR‐106b family—target CDKN1A mRNA, undermining its expression and tipping the balance toward unchecked proliferation and resistance to transforming growth factor β–mediated cytostasis (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Under conditions of metabolic stress, transient p53–p21 activation mediates a reversible cell cycle arrest that refocuses cellular metabolism toward antioxidant defense, thereby promoting survival (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In the context of cellular senescence, robust and sustained expression of p21 establishes a feedback loop that couples mitochondrial dysfunction and reactive oxygen species production to the maintenance of a deep senescent state (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, abrogation of positive cell cycle drivers such as E2F results in p21 accumulation, further consolidating the irreversible arrest of cell proliferation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In breast cancer, for example, estrogen receptor β activation leads to upregulation of p21 (along with other inhibitors) to arrest cell cycle progression and inhibit tumor formation (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", while transcriptional networks involving KLF4 can modulate p21 levels to dictate the balance between growth suppression and transformation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, p21 can also exert antioxidant effects by binding to and stabilizing Nrf2, thereby contributing to cellular defense against oxidative damage (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these studies demonstrate that CDKN1A/p21 is a central effector of tumor‐suppressive pathways that not only mediates cell cycle arrest in response to genomic and metabolic stress but also influences differentiation, senescence, and the cellular response to environmental cues.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marc van de Wetering, Elena Sancho, Cornelis Verweij, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(02)01014-0"}], "href": "https://doi.org/10.1016/s0092-8674(02"}, {"type": "t", "text": "01014-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12408868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12408868"}]}, {"type": "r", "ref": 2, "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": 3, "children": [{"type": "t", "text": "Takatsugu Ishimoto, Osamu Nagano, Toshifumi Yae, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2011.01.038"}], "href": "https://doi.org/10.1016/j.ccr.2011.01.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21397861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21397861"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Joan Seoane, Hong-Van Le, Lijian Shen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "HIF-1alpha induces cell cycle arrest by functionally counteracting Myc."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600196"}], "href": "https://doi.org/10.1038/sj.emboj.7600196"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15071503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15071503"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Fabio Petrocca, Rosa Visone, Mariadele Rapazzotti Onelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2008.02.013"}], "href": "https://doi.org/10.1016/j.ccr.2008.02.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18328430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18328430"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Irena Ivanovska, Alexey S Ball, Robert L Diaz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01977-07"}], "href": "https://doi.org/10.1128/MCB.01977-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18212054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18212054"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Oliver D K Maddocks, Celia R Berkers, Susan M Mason, et al. 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Synonyms	CIP1, MDA-6, P21CIP1, CAP20, CDKN1, SDI1, WAF1
Proteins	CDN1A_HUMAN
NCBI Gene ID	1026
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CDKN1A has 24,038 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 122 datasets.

Click the + buttons to view associations for CDKN1A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CDKN1A 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 CDKN1A 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 CDKN1A 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 CDKN1A 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 CDKN1A 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 CDKN1A 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 CDKN1A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CDKN1A protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CDKN1A 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 CDKN1A 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 CDKN1A 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 CDKN1A 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 CDKN1A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CDKN1A gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CDKN1A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CDKN1A 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 CDKN1A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CDKN1A 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 CDKN1A 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 CDKN1A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CDKN1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CDKN1A 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 CDKN1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	CORUM Protein Complexes	protein complexs containing CDKN1A protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CDKN1A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CDKN1A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CDKN1A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CDKN1A gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CDKN1A gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CDKN1A 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 CDKN1A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CDKN1A gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CDKN1A 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 CDKN1A 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 CDKN1A 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 CDKN1A 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 CDKN1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CDKN1A 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 CDKN1A 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 CDKN1A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CDKN1A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.