TP53

HIGH

Tumor protein p53

Chromosome: 17p13.1

Gene Overview

TP53 encodes p53, a critical tumor suppressor that coordinates cellular responses to DNA damage, oncogenic stress, and other insults. p53 arrests the cell cycle, promotes DNA repair, or induces apoptosis depending on context. Germline TP53 mutations cause Li-Fraumeni syndrome with high cancer risk. Somatic TP53 mutations occur in >50% of human cancers, including breast and lung. p53 regulates hundreds of targets including p21, PUMA, and Bax. The protein is normally short-lived; stress stabilizes it. MDM2 targets p53 for degradation. Expression is ubiquitous. TP53 status influences therapeutic response; mutant p53 can acquire gain-of-function properties that promote metastasis.

Molecular Function

  • transcriptional activation
  • DNA binding
  • cell cycle arrest
  • apoptosis induction

Protein class: tumor suppressor

Regulatory Annotation

Promoter activity: Constitutive transcription; p53 autoregulation.

Enhancer associations: Cancer-associated variants in regulatory regions.

Methylation sensitivity: Rare promoter methylation in some cancers.

eQTL tissues: lung, breast

Tissue Expression Context

lungTPM range: 5-20GTEx vv8
breastTPM range: 4-18GTEx vv8

Pathways

Linked Diseases & Exposures

Diseases

Exposures

  • tobacco— literature, strength 0.92

Mechanistic Hypotheses

TP53 loss permits survival of cells with DNA damage; in tobacco-exposed lung, p53 mutations enable clonal expansion of damaged epithelial cells; combined genetic and environmental DNA damage drives carcinogenesis.

TP53 mutations frequent in smoking-related lung cancer; characteristic G→T transversions at smoke-derived adducts.

HIGH

Confidence Rating

Overall evidence confidence for this gene entry: HIGH

References

  1. 1.Vousden KH, Prives C (2009). p53 in health and disease. Nature Reviews Molecular Cell Biology. doi:10.1038/nrm2716
  2. 2.GTEx Consortium (2020). GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. doi:10.1126/science.aaz1776
  3. 3.Alexandrov LB, et al. (2016). Mutational signatures of tobacco smoking in human cancer. Science. doi:10.1126/science.aag0299