CDKN1A (p21/Cip1): A Key Cyclin-Dependent Kinase Inhibitor and Tumor Suppressor
Explore the genomic context, expression patterns, disease associations, and functional significance of the CDKN1A gene, a master regulator of the cell cycle and stress response.
Gene Information Card
| Symbol | CDKN1A |
|---|---|
| Full Name | Cyclin Dependent Kinase Inhibitor 1A |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.2 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000124762 |
| UniProt ID | P38936 |
| OMIM ID | 116899 |
| HGNC ID | 1784 |
| Aliases | p21, CIP1, WAF1, CAP20, CDKN1, MDA-6, SDI1 |
Description
The CDKN1A gene encodes p21/Cip1, a potent cyclin-dependent kinase inhibitor (CKI) that regulates cell cycle progression at the G1/S checkpoint. It is a primary transcriptional target of p53 and mediates cell cycle arrest, senescence, and DNA repair in response to cellular stress. Beyond its canonical role, p21 also influences apoptosis, transcription, and cytoskeletal dynamics. Its expression is tightly regulated and frequently altered in cancer, making it a critical tumor suppressor and a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Loss of p21 expression or function leads to unchecked cell proliferation and genomic instability, contributing to tumorigenesis. | High frequency of reduced p21 expression in many cancers; somatic mutations are rare but functional inactivation occurs via p53 loss or epigenetic silencing. |
| Li-Fraumeni syndrome | Germline TP53 mutations impair p21 induction, predisposing to multiple cancers. | CDKN1A itself is not commonly mutated, but its pathway is disrupted. |
| Atherosclerosis | p21 promotes vascular smooth muscle cell senescence, influencing plaque stability. | Expression studies in human atherosclerotic plaques. |
| Premature aging | Altered p21 activity affects cellular senescence and aging phenotypes. | Mouse models with p21 overexpression show accelerated aging. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 31.2 | High |
| Spleen | 28.5 | High |
| Bone marrow | 24.1 | High |
| Lung | 12.3 | Medium |
| Liver | 8.7 | Medium |
| Brain | 5.2 | Low |
| Muscle | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 45.6 | Cervical cancer cell line; high expression due to HPV E6-mediated p53 degradation? Actually p21 is low; but data may vary. |
| A549 | 22.3 | Lung carcinoma; moderate expression |
| MCF7 | 18.9 | Breast cancer; p53 wild-type, inducible p21 |
| HCT116 | 35.4 | Colorectal cancer; p53 wild-type, high basal p21 |
| U2OS | 27.8 | Osteosarcoma; p53 wild-type, moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.31C>T (p.Arg11Trp) | Missense | Rare (<0.1%) | May affect protein stability or interaction with PCNA; clinical significance uncertain. |
| c.98C>T (p.Pro33Leu) | Missense | Rare | Reported in some cancers; functional impact not fully characterized. |
| c.93G>A (p.Trp31Ter) | Nonsense | Very rare | Truncated protein likely non-functional; associated with loss of cell cycle control. |
| c.IVS2+1G>A | Splice site | Rare | May cause exon skipping and loss of function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CDKN1A are rare but can lead to reduced p21 activity, impairing cell cycle arrest and promoting tumorigenesis. Examples include nonsense and frameshift mutations that truncate the protein.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; p21 overexpression can paradoxically promote cell survival in certain contexts, but this is typically due to regulatory changes rather than mutations.
Dominant Negative (DN)
Dominant-negative mutations have been proposed but not clearly identified in CDKN1A. Some missense variants may interfere with protein-protein interactions, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • cyclin-dependent protein serine/threonine kinase inhibitor activity | • protein binding |
| • DNA binding | • transcription factor binding |
| • cell cycle arrest | • negative regulation of cell cycle |
| • response to DNA damage stimulus | • cellular senescence |
| • apoptotic process | • regulation of transcription by RNA polymerase II |
Pathways
• p53 signaling pathway
• Cell cycle: G1/S checkpoint
• Senescence and autophagy
• DNA damage response
• Notch signaling
• TGF-beta signaling
Protein Summary
The p21 protein (21 kDa) is a cyclin-dependent kinase inhibitor that binds to and inhibits the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, thereby regulating cell cycle progression at G1/S. It also interacts with proliferating cell nuclear antigen (PCNA) to modulate DNA replication and repair. p21 is a key effector of p53-mediated growth arrest and senescence. Its subcellular localization (nuclear vs. cytoplasmic) influences its function, with nuclear p21 promoting cell cycle arrest and cytoplasmic p21 having anti-apoptotic effects. Post-translational modifications, such as phosphorylation and ubiquitination, regulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDKN1A Knockout HEK293 Cell Line | EDJ-KQ129 | Human | 1026 | Details Get a Quote |
| CDKN1A Knockout HeLa Cell Line | EDJ-KQ18296 | Human | 1026 | Details Get a Quote |
| CDKN1A Knockout A-549 Cell Line | EDJ-KQ18755 | Human | 1026 | Details Get a Quote |
| CDKN1A Knockout HCT 116 Cell Line | EDJ-KQ18757 | Human | 1026 | Details Get a Quote |
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