Analysis and description of this recent release of the UMD p53 mutation database can be found here:
Problems and bias associated with the publication of p53 mutations have been fully described.
Each row in the table represents a single mutation arbitrarily assigned with a unique identification number.
Files have been sorted by reference number
||Unique identification number for this mutation
||Nucleotide position using the p53 cDNA as a reference (1 is the A of the start ATG)
||Codon position (1 to 393)
||Mutations/variations in intron are not included in the UMD p53 database as the majority of them have not been associated with splicing defects.
||Normal base sequence of the codon in which the mutation occurred
||Sequence of the mutated codon. If the mutation is a deletion or an insertion, it is indicated by "del" or "ins" followed by the number of deleted or inserted bases. The position in the codon is indicated by “a”, “b”, or “c” for the first, second or third base of the codon respectively. Example: "del66b" is a deletion of 66 bases including the second base of the codon; "ins4a" is an insertion of 4 bases occurring between the first and the second base of the codon. Label a, b, or c is omitted if the boundary of the deletion or insertion is unknown.
||Wild type amino acid
||Mutant amino acid. Stop: nonsense mutation: Fs.: Frameshift mutation: InF: In-frame insertion or deletion
||Name of the tumor/patient/cell line as given by the authors. If the publication does not include any sample name, we have arbitrarily assigned a name, usually the first letters of the last author's name, followed by the numbers in the series. The same name or number can occur several times in a single study as in some samples more than one mutation has been reported (see complexity to find samples with multiple mutations).
For cell lines, we used the name given in the publication. Unfortunately, there is some confusion as similar cell lines can appear with multiple names (acronym or ATCC references, change/errors in the acronym). Care has been taken to ensure some homogeneity
||Mutation: the nucleotide variation is associated with a change of the amino-acid: Polymorphism: the nucleotide variation is not associated with a change in the amino-acid sequence.
||Exonic mutations that do not changed amino acid sequences are not always neutral. The p53 mutation at codon 125 (ACG->ACA, T125T) was described by many authors as a polymorphic variant. RNA analysis of this mutation, located at the 3’ extremity of exon 4, shows that the splicing of the p53 gene is totally aberrant (Warneford et al., 1992)
||Mutational event: G>C: (G to C base change); C->A/C->T: complex mutation that change two nucleotide in the codon (C to A and C to T base change); Stop at 344: frameshift mutation leading to a premature stop codon and the synthesis of a truncated protein of 344 residues;
In frame del or In frame Ins: deletion/insertion of that do not change the open reading frame of the p53 protein.
||Ts: Transition (a pyrimidine (C or T) is substituted by another pyrimidine, or a purine (A or G) is substituted by another purine); Tv: Transversion (a transversion mutation involves the change from a pyrimidine to a purine, or vice versa); Fr: Frameshift mutations (deletion / insertion); Ts/Ts: for mutation that target two nucleotides in the same codon; InF: deletion/insertion of that do not change the open reading frame of the p53 protein.
||SM: Single mutational event in the tumor; DMU (Double Mutation Unknown): Two p53 mutations in the same tumor but their allelique distribution is unknown; DMD (Double Mutation Different allele): Two p53 mutations in the same tumor on two different p53 allele; DMD (Double Mutation Same allele): Two p53 mutations in the same tumor on the same p53 allele: MM (Multiple Mutation): More than two p53 mutations in the same tumor.
||B: single missense mutation; F: single nucleotide insertion or deletion; D: Deletion (2 or more nucleotides); I: insertion (2 or mores nucleotides); T: tandem mutation
||Yes: transition (G to A or C to T base change) at a CpG dinucleotide; No: transitions (G to A or C to T base change) at non CpG Sites and all transversion
||Indicates whether or not a mutation target a Py-Py doublet
Py-Py doublet: two adjacent pyrimidine residues (cytosine or thymine) that can be targeted by UV light.
Yes, non coding strand: mutation localized at a Py-Py doublets on the non coding strand of the p53 gene; Yes, coding strand: mutation localized at a Py-Py doublets on the coding strand of the p53 gene; No: mutation localized outside a Py-Py doublet
||Post-translational modifications of the codon: phosphorylation (Ser or Thr); ubiquitination; neddylation; methylation; acetylation
||HCD I to V: Highly Conserved Domain I to V; DNA Binding: DNA binding domain: Negative regulation: carboxy-terminus of the p53 protein associated with a negative regulation of for p53 DNA binding activity; Transactivation: transactivation domain of the p53 protein; Proline Rich: Proline rich domain of the p53 protein; NES: Nuclear export signal of p53; NLS: Nuclear localization signal of p53; oligomerization: Tetramerization domain of the p53 protein.
||Origin of the sample with the p53 mutations; Tumor: tumor tissue (biopsy, surgical specimen, cytology specimen) from cancer patients; Cell line: self explanatory; For cell lines, when the status of the original tumor is also known, a second entry with the same name but labeled as « tumor » is included in the database; Germline: constitutional p53 mutation associated with familial cancer such as Li-Fraumeni syndrome (LFS), Li-Fraumeni like syndrome (LFSL).
||Tumors can occur in patients with particular syndromes or with known germline mutations in other tumor suppressor genes or after.
BRCA1: patients with a germline mutation in the BRCA1 gene
BRCA2: patients with a germline mutation in the BRCA2 gene
XP-C: Xeroderma Pigmentosum type C
XP-D: Xeroderma Pigmentosum type D
XP-E: Xeroderma Pigmentosum type E
XP-V: Xeroderma Pigmentosum variant
PTEN: patients with a germline mutation in the Phosphatase and TENsin homolog gene associated with a Cowden disease
CHK2: patients with a germline mutation in the checkpoint kinase 2 gene associated with a Li-Fraumeni syndrome
FA-C: Fanconi anemia type C
Familial Breast cancer: familial cancer with no mutation identified
PTCH: patients with a germline mutation in the patched gene
P152L gl mutation: Patients with a p53 germline mutation at codon 152 and prone for adrenocortical tumors with several secondary p53 mutations in their tumors.
NF1: patients with a germline mutation in the NF1 gene
RDEB: patients with recessive dystrophic epidermolysis bullosa
HNPCC: hereditary non polyposis colon cancer
||Solid: Non hematological tumor
Leu: all leukemia and lymphoma
||Int.: all internal tumors
Skin: all skin tumors
||Information on the smoking status of the patient
Yes, No, Unknown or Ex smoker
||Exposition of the patient to Aflatoxin B1: Yes, No or Unknown
||Exposition of the patient to radiation: Yes, No or Unknown
||Information on the drinking status of the patient
Yes, No or Unknown
||Exposition of the patient to Asbestos: Yes, No or Unknown
||Detection of HBV in the tumor; Yes, No or Unknown
||Detection of HPV in the tumor; Yes, No or Unknown
||Germline genotype at codon 72 (exon 4): Arg/Arg, Arg/Po or Pro/Pro
||Genotype of codon 72 associated with the p53 mutant: Arg or Pro.
|Number of records
||Number of tumors with this particular mutant the database
||Reference identification number
|Mutant activities (mutant)
Data on AQ to AX columns are taken from the work of Kato et al.,( Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C (2003) 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 100: 8424-8429).
Transactivation was tested using a yeast assay. The residual transcriptional activity of mutant p53 is always compared to wild type p53 for the same promoter (%).
Wt: mutation that does not change the amino acid: Be aware that some of these mutation can change splicing or RNA stability
Fr: Frameshift mutations. No activity data is available but it is usually assumed that no p53 is produced
Tr: Terminating mutation: No activity data is available but it is usually assumed that no p53 is produced
ND: No data available for this mutant
||Residual transcriptional activity of mutant p53 on the WAF1 promoter (% compared to wild type p53).
||Residual transcriptional activity of mutant p53 on the MDM2 promoter (% compared to wild type p53).
||Residual transcriptional activity of mutant p53 on the BAX promoter (% compared to wild type p53).
||Residual transcriptional activity of mutant p53 on the 14-3-3-s promoter (% compared to wild type p53).
||Residual transcriptional activity of mutant p53 on the AIP promoter (% compared to wild type p53).
||Residual transcriptional activity of mutant p53 on the GADD45 promoter (% compared to wild type p53).
||Residual transcriptional activity of mutant p53 on the NOXA promoter (% compared to wild type p53).
||Residual transcriptional activity of mutant p53 on the p52R2 promoter (% compared to wild type p53).
||Mutant names using the official nomenclature as define by Antonorakis et al. (den Dunnen JT & Antonorakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion. Hum Mutat 2000; 15: 7-12)
||Out of range studies using either 95 ou 99% as a cut-off