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Gene | TP53 |
Variant | R273H |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | TP53 R273H lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R273H results in increased proliferation, migration, invasion, and protein stability in culture (PMID: 37030635), increased Tbk1 interaction 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 loss of DNA binding, decreased Tp53 target gene expression, apoptosis resistance, and failure of G1 arrest in culture (PMID: 31395785), and confers a gain of function to Tp53 resulting in aberrant transcriptional activation and increased 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 |
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_000546.6 | 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_001407264.1 | 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_001126114 | 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_001126114.3 | chr17:g.7673802C>T | c.818G>A | p.R273H | RefSeq | GRCh38/hg38 |
NM_001126114.2 | 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_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_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_001126113.2 | 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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
TP53 R273H | 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 R273H in culture (PMID: 26086967). | 26086967 |