+This track shows variants of the human TP53 tumor-suppressor gene from the +UMD TP53 database, a locus-specific +variant database maintained by Thierry Soussi and Bernard Leroy. It is a +comprehensive, curated resource for TP53 mutations in human cancer, +integrating data from tumours, cell lines, germline (Li-Fraumeni syndrome and other +hereditary conditions), and non-neoplastic diseases reported in the published +literature. +
+ ++The track is built from the database's variant file, which lists each unique +TP53 variant once. For every variant the database provides curated +metadata including a pathogenicity classification, the residual transactivation +activity of the mutant protein on eight p53 target promoters, functional impact +predictions from multiple algorithms (SIFT, PolyPhen-2, MutationAssessor, PROVEAN, +Condel, MutPred Splice), and frequencies in tumours, cell lines, somatic samples, +and germline cases. +
+ ++TP53 hot spots such as p.R175H, p.R248Q, p.R248W, p.R273H, p.R273C, and +p.R282W are visible as the densely-recurrent positions in the DNA-binding domain. +
+ ++Each variant is shown as a single coloured box at its genomic position. The colour +encodes the database's pathogenicity classification: +
+ +| Pathogenic | |
| Likely Pathogenic | |
| Possibly pathogenic | |
| VUS (variant of uncertain significance) | |
| Benign | |
| Unknown |
+Hovering over a variant displays its HGVS cDNA name, protein change on the canonical +TP53 alpha isoform (NP_000537.3), pathogenicity call, effect class, tumour frequency, +total occurrence count, and the curator note on residual transactivation activity. +Clicking opens the full details page with the per-promoter activity values, all +algorithm-level predictions and scores, the structural domain annotation, links to +COSMIC and dbSNP, and the curator's final comment. +
+ ++The track configuration page supports filters on: +
+ ++Variants can be searched from the position box by HGVS cDNA name +(e.g. c.524G>A) or by canonical protein change (e.g. p.R175H). +
+ ++The track is rebuilt automatically when a new release of the UMD TP53 database is +detected at p53.fr. +
+ +
+The raw data can be explored interactively with the
+Table Browser or the
+Data Integrator. The underlying
+bigBed file may be downloaded directly
+from /gbdb/$db/bbi/umdTp53/umdTp53.bb, and the data can be
+queried programmatically through the
+REST API via the track name
+umdTp53.
+
+The variants file from p53.fr (UMD_variants_US.tsv, one row per unique
+TP53 variant) was reformatted to
+bigBed. For hg19, genomic coordinates
+were taken directly from the variants file's HG19_Start and
+HG19_End columns. The variants file does not ship hg38 coordinates, so
+for hg38 the coordinates were joined from the companion mutations file
+(UMD_mutations_US.tsv), which contains both hg19 and hg38 positions for
+every variant.
+
+The curator's residual-activity comment column derives from the eight-promoter +transactivation assay of Kato et al., 2003: for missense variants, the +median of the eight per-promoter activities (expressed as % of wild-type) is mapped +to one of Fully active, Hyper active, Partial activity, +No activity, or No data. For nonsense, frameshift, splice-site, and +similar variants where the assay does not directly apply, the column carries an +explanatory note (e.g. The activity of truncated p53 is assumed to be nil). +The eight raw per-promoter values are available on the details page. +
+ ++Thanks to Thierry Soussi, Bernard Leroy, and the UMD TP53 database curators for +maintaining the resource and making it available for download. +
+ ++Leroy B, Anderson M, Soussi T. + +TP53 mutations in human cancer: database reassessment and prospects for the next +decade. +Hum Mutat. 2014 Jun;35(6):672-88. +PMID: 24665023 +
+ ++Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C. + +Understanding the function-structure and function-mutation relationships of p53 +tumor suppressor protein by high-resolution missense mutation analysis. +Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. +PMID: 12826609; +PMC: PMC166245 +