TP53
Chr 17ADSomatictumor protein p53
Also known as: BCC7, BMFS5, LFS1, P53, TRP53
The protein is a tumor suppressor that regulates gene expression in response to cellular stress, inducing cell cycle arrest, apoptosis, DNA repair, or metabolic changes. Mutations cause Li-Fraumeni syndrome and predispose to multiple pediatric cancers including adrenocortical carcinoma, osteosarcoma, and choroid plexus papilloma through autosomal dominant inheritance. The pathogenic mechanism involves loss of function of this critical tumor suppressor.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TP53 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer
ACTIVE NOT RECRUITINGLi-Fraumeni Syndrome/TP53 Biobank
RECRUITINGClinical and Genetic Studies of Li-Fraumeni Syndrome
RECRUITINGEntrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia
ACTIVE NOT RECRUITINGMRI Radiomics Combined With Pathomics on the Prediction of Molecular Classification and Prognosis of Endometrial Cancer
NOT YET RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGMolecular Genetics Guide the Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation
RECRUITINGctDNA Assay in Patients With Resectable Pancreatic Cancer
RECRUITINGOsimertinib Monotherapy or Combination With Chemotherapy for Advanced NSCLC Concurrent EGFR and TP53 Mutations
ACTIVE NOT RECRUITINGA Study of BN104 in the Treatment of Acute Leukemia
ACTIVE NOT RECRUITINGFeasibility of Targeted Bronchial Washing for Molecular Testing by Next Generation Sequencing in Early-stage Lung Cancer
ACTIVE NOT RECRUITINGDetection of Minimal Residual Disease Post-prostatectomy
RECRUITINGExternal Resources
Links to major genomics databases and tools