TP53 Sequences
Reference sequences used to annotate TP53 gene variations
- Graphical view of the Genomic sequence (hg38) with exon-intron boundaries for the main p53 isoform.
- Coding and protein sequence with residue numbers, amino-acids, highlighted CpG sites and exon-intron boundaries.
- NCBI link to cDNA sequence corresponding to the NM_000546 isoform.
Other links to human sequences
Sequences in other species
3D Sequence Structures
- Download p53 core domain and Rasmol viewer
- p53 core domains bound to DNA
- p53 core domain bound to the ankyrin and SH3 domains of 53BP2
- p53 core domain bound to the Brct Region of 53Bp1
- p53 core domains (2) bound to the Brct Regions (2) of 53Bp1
- p53 tetramerization domain (residues 326-356)
- p53 tetramerization domain (X-ray)
- p53 transactivation domain bound to mdm2
Variant Nomenclatures
The genomic reference sequence used for annotating TP53 variants is NC_000017.11 (hg38 build) from GenBank.
Variants are reported according to HGVS nomenclature recommendations.
We recommend to use Mutalyzer, to help
you
format your variant data according to HGVS guidelines and to convert positions between
different
genome build or isoforms.
Protocols and Tools
Protocols
To assess TP53 variant status it is recommended to perform gene sequencing of all
exons,
including
the splice junctions and completed with MLPA to detect large deletion/duplications.
Immuno-histochemical analysis is not a good method for assessing TP53 variant
status,
as
it cannot
distinguish between the various types of variants, does not detect truncating variants
(false-negative results), and gives
false-positive results (over-expressed WT protein).
Some Example of Sequencing Protocols:
- Direct Sequencing by Sanger: TP53_SangerSequencing_NIH.pdf
- TP53 sequencing by a next generation sequencing technology (NGS). The detailed list of primers can be downloaded here: NGS_TP53_Primers.txt
- MLPA
- Some caution regarding TP53 variants detected by multigene panel testing by NGS: a study by Weitzel et al.
- Sequencing and Haplotyping: TP53_SNP_sequencing.pdf
Recent developments on p53 antibodies
Other tools
- Mutalyzer, a package to support checks of sequence variant nomenclature according to the guidelines of the Human Genome Variation Society
- Resources for the systematic analysis of p53 interactions with DNA and other transcription factors.
- p53retriever, for the detection and display of p53 putative response elements (REs) on DNA sequences
- TargetGeneReg, for displaying gene of interest in the p53 and cell cycle gene regulatory networks
- TP53 RNA expression data from TCGA at GEPIA
- Datamed, a search engine for TP53 datasets
- Align-AGVGD, for the prediction of the functional impact of missense variants
- SIFT, for the prediction of the functional impact of missense variants
- Scorecons, for scoring residue conservation
- The Cancer Genome Interpreter, to identify driver variants in tumor samples
- LFSPRO, a tool for estimating TP53 Variant Carrier Probability
- Famdenovo, an algorithm that calculates the probability of a germline variant to be de novo based on family history data
- Amino-acid letter codes and properties
- Genetic code
- LOVD, a software to build variant databases
3D Structures Analysis
3D Viewer
Use mouse or control buttons (located on the right)
to
explore.
Structural Impacts of Variants
- Analysis by A.C. Martin: Publication
- Analysis by Mathe (2006). See details here: Structure-Function Predictions Based on Scores Derived from Delaunay Tessellations
- UniProt information
- Stability and oligomeric structure of p53 tetramerization domain mutants by Kamada et al. (2011)
- Solved crystal structures:
- by Joerger AC et al. (2005)
- M133L/V203A/N239Y/N268D
- M133L/V203A/N239Y/N268D/R273H
- M133L/H168R/V203A/N239Y/N268D
- M133L/V203A/N239Y/R249S/N268D
- M133L/H168R/V203A/N239Y/R249S/N268D
- T123A/M133L/H168R/V203A/N239Y/R249S/N268D
- by Joerger AC et al. (2006)
- M133L/V143A/V203A/N239Y/N268D
- M133L/V203A/Y220C/N239Y/N268D
- M133L/V203A/G245S/N239Y/N268D
- M133L/V203A/N239Y/N268D/F270L
- M133L/V203A/N239Y/N268D/R273C
- M133L/V203A/N239Y/N268D/R282W
- Thermodynamic Stability Data
Definitions and Functions
- TP53 entry at EntrezGene
- OMIM review at NCBI
- TP53 GeneCards entry
- P53 Signaling Pathway
- p53 target genes and response-elements
- Gene annotation by Ensembl at EBI
- p53 entry at Atlas of Genetics
- p53 protein interactions at Human Protein Reference Database
- p53 post-translational modifications at Human Protein Reference Database
- p53 isoforms
- Protein annotation by SwissProt/UniProtKB
- p53 history and info by Thierry Soussi
- TP53 family memmbers: TP63 and TP73
p53 in the Clinic
- Li-Fraumeni syndrome at GeneReviews
- Videocast of the Li-Fraumeni Syndrome Workshop 2010
- p53 in clinical trials at ClinicalTrials.gov
- "p53 in the clinics" book, 2012
- LFSPRO, a tool for estimating TP53 Variant Carrier Probability
- Famdenovo, an algorithm that calculates the probability of a germline variant to be de novo, taking TP53 as an example application
Other Databases
TP53 databases
There are several links to different TP53 databases available on the web. Several resources are not updated anymore and may contain obsolete data. It is recommended to use up-to-date resources.
- The TP53 Database (last updated in July 2019)
- The p53 database by Thierry Soussi (last updated in 2017)
- LOVD TP53, a database system for direct data submission
- The database of germline TP53 mutations in Prague (not updated anymore)
- p53 Knowledgebase at Singapore (obsolete)
- Human p53 database and software, N. Cariello (1997) (obsolete)
Related Databases
- Catalogue Of Somatic Mutations in Cancer (COSMIC) at Sanger Institute, UK
- International Cancer Genome Consortium (ICGC) data portal
- cBioPortal for Cancer Genomics
- AACR GENIE dataset in cBioportal
- TCGA data portal
- List of locus specific databases
- St. Jude PeCan Data Portal on pediatric cancer mutations