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Gene | TP53 |
Variant | R248Q |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | TP53 R248Q is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R248Q results in increased proliferation, migration, invasion, and protein stability and altered subcellular localization in culture (PMID: 37030635), loss of DNA binding and decreased transactivation of Tp53 targets and interference with wild-type Tp53 transactivation, leads to resistance to apoptosis and failure of G1 arrest in cell culture (PMID: 23538418, PMID: 16861262, PMID: 31395785), as well as increased Akt activation, Stat3 dependent migration, and enhanced tumor onset and growth in mouse models (PMID: 30107178). |
Associated Drug Resistance | |
Category Variants Paths |
TP53 mutant TP53 exon7 TP53 R248Q TP53 mutant TP53 inact mut TP53 R248Q |
Transcript | NM_000546.6 |
gDNA | chr17:g.7674220C>T |
cDNA | c.743G>A |
Protein | p.R248Q |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000546.6 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126114.2 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001407262.1 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001407268.1 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126113.3 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126112 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001407264.1 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126112.3 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_000546.5 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126113 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001407270.1 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126114 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126113.2 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001407266.1 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126114.3 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_000546 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
NM_001126112.2 | chr17:g.7674220C>T | c.743G>A | p.R248Q | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
TP53 I195* TP53 R248Q | ovarian carcinoma | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, ReACp53 induced cell death and decreased proliferation of human primary ovarian carcinoma cells harboring both TP53 I195* and TP53 R248Q in culture (PMID: 26748848). | 26748848 |
MDM2 pos TP53 R248Q | triple-receptor negative breast cancer | sensitive | YX-02-030 | Preclinical - Patient cell culture | Actionable | In a preclinical study, YX-02-030 decreased survival in a triple-negative breast cancer (TNBC) cell line harboring TP53 R248Q in culture, decreased Mdm2 expression and increased apoptosis in patient-derived TNBC explants in culture, and increased apoptosis and decreased survival in 3D mammosphere cultures (PMID: 36734633). | 36734633 |
MDM2 pos TP53 R248Q TP53 R267L TP53 R273H | triple-receptor negative breast cancer | sensitive | YX-02-030 | Preclinical - Patient cell culture | Actionable | In a preclinical study, YX-02-030 decreased Mdm2 expression and increased apoptosis in patient-derived triple-negative breast cancer explants harboring TP53 R248Q, R267L, and R273H in culture (PMID: 36734633). | 36734633 |