Gene Variant Detail

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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 a 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 inact mut TP53 R248Q

TP53 mutant TP53 exon7 TP53 R248Q

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Transcript NM_000546.5
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_001126113 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
NM_000546.5 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_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_000546 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

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 R248Q ovarian cancer sensitive ReACp53 Preclinical - Pdx & cell culture Actionable In a preclinical study, ReACp53 rescued p53 activity and decreased viability of ovarian cancer cells harboring TP53 R248Q in culture, and induced tumor regression in patient-derived ovarian cancer xenograft models harboring TP53 R248Q (PMID: 26748848). 26748848
TP53 R248Q ovarian cancer sensitive APR-246 + Cisplatin Preclinical Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of a Platinol (cisplatin)-resistant ovarian cancer cell line harboring TP53 R248Q in culture and inhibited tumor growth in TP53 R248Q-carrying ovarian cancer cell line xenograft models (PMID: 26086967). 26086967
TP53 R248Q Advanced Solid Tumor sensitive Ganetespib Preclinical Actionable In a preclinical study, Ganetespib extended survival by 48% in mice with tumors expressing TP53 R248Q (PMID: 26009011). 26009011
TP53 R248Q acute myeloid leukemia resistant ALRN-6924 Preclinical - Cell culture Actionable In a preclinical study, ALRN-6924 did not inhibit the growth of acute myeloid leukemia cells harboring TP53 R248Q in culture (PMID: 29643228). 29643228
TP53 R248Q colorectal cancer sensitive Tanespimycin Preclinical Actionable In a preclincal study, Tanespimycin (17-AAG) treatment reduced p-Stat3 expression, induced apoptosis, and inhibited tumor growth of mutagen induced colorectal cancer in a genetic mouse model expressing TP53 R248Q (PMID: 30107178). 30107178
TP53 R248Q colorectal cancer predicted - sensitive Napabucasin Preclinical - Cell culture Actionable In a preclinical study, Napabucasin (BBI608) treatment reduced Stat3 phosphorylation and impaired wound healing in colorectal cancer cell lines expressing TP53 R248Q in culture (PMID: 30107178). 30107178
TP53 R248Q acute myeloid leukemia predicted - sensitive thioureidobutyronitrile Preclinical - Cell culture Actionable In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in apoptosis, decreased cell viability, elevated expression of Tp53 target genes, and increased Tp53 nuclear localization in an acute myeloid leukemia cell line harboring TP53 R248Q in culture (PMID: 32945487). 32945487