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Gene | TP53 |
Variant | R280K |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | TP53 R280K lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R280K results in interaction with Tbk1 leading to decreased Tbk1 and Irf3 phosphorylation and loss of Irf3 activation in culture (PMID: 33545063), decreased activation and repression of wild-type Tp53 target genes (PMID: 17070499, PMID: 16322760, PMID: 18472962), as well as a gain of function in activation of novel targets, and leads to increased cell migration and invasion, and increased cell survival (PMID: 18472962, PMID: 24763051). |
Associated Drug Resistance | |
Category Variants Paths |
TP53 mutant TP53 act mut TP53 R280K TP53 mutant TP53 exon8 TP53 R280K |
Transcript | NM_000546.6 |
gDNA | chr17:g.7673781C>T |
cDNA | c.839G>A |
Protein | p.R280K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001126114 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001126112.3 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001126112.2 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001126113.2 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001407264.1 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001407268.1 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_000546 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001126114.3 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001407262.1 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001126113 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_000546.6 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001126112 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001126114.2 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_000546.5 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001407266.1 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001407270.1 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
NM_001126113.3 | chr17:g.7673781C>T | c.839G>A | p.R280K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
TP53 R280K | breast cancer | sensitive | Ganetespib | Preclinical | Actionable | In a preclinical study, Ganetespib inhibited growth of human breast cancer cells harboring TP53 R280K in culture (PMID: 26009011). | 26009011 |
TP53 R280K | ovarian cancer | sensitive | APR-246 + Cisplatin | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically in culture, resulting in reduced cell viability in patient derived ovarian cancer cells harboring TP53 R280K (PMID: 27179933). | 27179933 |
TP53 R280K | triple-receptor negative breast cancer | sensitive | YW3-56 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, YW3-56 inhibited proliferation of a human triple-negative breast cancer (TNBC) cell line harboring TP53 R280K in culture and inhibited tumor growth in TP53 R280K-mutant TNBC cell line xenograft models (PMID: 25612620). | 25612620 |