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| Gene | TP53 |
| Variant | R158G |
| Impact List | missense |
| Protein Effect | loss of function - predicted |
| Gene Variant Descriptions | TP53 R158G lies within the DNA-binding domain of the Tp53 protein (PMID: 21760703). R158G retains activation of Cdkn1a and results in DNA-binding similar to wild-type Tp53 in culture (PMID: 32350249) but leads to the loss of DNA-binding activity in an in vitro assay, interferes with transactivation by wild-type Tp73 in yeast (PMID: 9472631, PMID: 12917626), and results in reduced Pmaip1 transcription, increased motility and anchorage-independent cell growth in culture and increased tumor growth in a mouse model (PMID: 32350249), and therefore, is predicted to lead to a loss of Tp53 protein function. |
| Associated Drug Resistance | |
| Category Variants Paths |
TP53 mutant TP53 exon5 TP53 R158G TP53 mutant TP53 inact mut TP53 R158G |
| Transcript | NM_000546.6 |
| gDNA | chr17:g.7675140G>C |
| cDNA | c.472C>G |
| Protein | p.R158G |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_001126115.2 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126113 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001407270.1 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126116.2 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001407268.1 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126112.3 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126112 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126114 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126117 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126117.2 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126114.2 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_000546 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126113.3 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126116 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001407262.1 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126112.2 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126114.3 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126115 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126117.1 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001407264.1 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_000546.6 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_000546.5 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126116.1 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126113.2 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001126115.1 | chr17:g.7673752G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| NM_001407266.1 | chr17:g.7675140G>C | c.472C>G | p.R158G | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| TP53 R158G | lung non-small cell carcinoma | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human non-small cell lung carcinoma cells harboring TP53 R158G in culture (PMID: 21325073, PMID: 23980093). | 21325073 23980093 |