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Gene | TP53 |
Variant | R248W |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | TP53 R248W is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R248W results in interaction with Tbk1 leading to decreased Tbk1 and Irf3 phosphorylation and loss of Irf3 activation in culture (PMID: 33545063), disrupts Dnmt3a complex formation similar to wild-type Tp53 (PMID: 31640986), however, results in increased proliferation, migration, invasion, and protein stability and altered subcellular localization in culture (PMID: 37030635), increased tumorigenesis in mice, and leads to decreased ATM activation, resulting in increased genetic instability (PMID: 17417627, PMID: 14743206). |
Associated Drug Resistance | |
Category Variants Paths |
TP53 mutant TP53 exon7 TP53 R248W TP53 mutant TP53 inact mut TP53 R248W |
Transcript | NM_000546.6 |
gDNA | chr17:g.7674221G>A |
cDNA | c.742C>T |
Protein | p.R248W |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001126113.2 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001126114.2 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_000546.5 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001407264.1 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001407270.1 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001126112 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001407268.1 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001126114.3 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001126114 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001126112.3 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_000546 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001126113.3 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001126113 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001407266.1 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001126112.2 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_000546.6 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
NM_001407262.1 | chr17:g.7674221G>A | c.742C>T | p.R248W | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
TP53 R248W | lung non-small cell carcinoma | sensitive | APR-246 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of non-small lung cancer cells harboring TP53 R248W in culture (PMID: 26086967). | 26086967 |
TP53 R248W | colon carcinoma | predicted - sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in colon carcinoma cells harboring TP53 R248W compared to radiotherapy alone in culture, resulting in increased mitotic catastrophe; however, wild-type TP53 cells were more sensitive to the treatment combination than TP53 R248W mutant cells (PMID: 29769307). | 29769307 |