Gene Variant Detail

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Gene TP53
Variant R273H
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions TP53 R273H is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R273H disrupts Dnmt3a complex formation similar to wild-type Tp53 (PMID: 31640986), however, results in a loss of DNA binding and decreased activation of Tp53 target gene expression, leads to resistance to apoptosis and failure of G1 arrest in cell culture (PMID: 31395785), and also confers a gain of function to Tp53, resulting in aberrant transcriptional activation and increased cell migration (PMID: 22114072, PMID: 14743206, PMID: 32002804).
Associated Drug Resistance
Category Variants Paths

TP53 mutant TP53 exon8 TP53 R273X TP53 R273H

TP53 mutant TP53 inact mut TP53 R273H

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Transcript NM_000546.6
gDNA chr17:g.7673802C>T
cDNA c.818G>A
Protein p.R273H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001126114.2 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001407262.1 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001407266.1 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_000546.6 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001126113.3 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001126114 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001126113.2 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001126114.3 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001407268.1 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001407270.1 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001126112 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_000546 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_000546.5 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001126112.3 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001126113 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001126112.2 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38
NM_001407264.1 chr17:g.7673802C>T c.818G>A p.R273H RefSeq GRCh38/hg38

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  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 R273H TP53 P309S colorectal cancer sensitive NSC59984 Preclinical - Cell culture Actionable In a preclinical study, treatment with NSC59984 induced Tp53 pathway signaling, degradation of mutant Tp53, and cell death in a colorectal cancer cell line harboring TP53 R273H and TP53 P309S in culture (PMID: 26294215). 26294215
TP53 R273H TP53 P309S colorectal cancer sensitive Cisplatin + NSC59984 Preclinical - Cell culture Actionable In a preclinical study, the combination of Platinol (cisplatin) and NSC59984 worked synergistically to decrease viability of a colorectal cancer cell line harboring TP53 R273H and TP53 P309S in culture (PMID: 26294215). 26294215
BRAF V600E PIK3CA P449T TP53 R273H colorectal cancer sensitive PD-0325901 + Sapanisertib Preclinical - Cell line xenograft Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and growth of colorectal cancer cells harboring BRAF V600E, PIK3CA P449T, and TP53 R273H in culture and in cell line xenograft models, but did not have synergistic effect on apoptosis (PMID: 26272063). 26272063