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Gene | TP53 |
Variant | R175H |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | TP53 R175H is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R175H leads to increased Nek2 expression in culture (PMID: 35088582) and results in a loss of DNA binding, decreased activation of Tp53 targets and interferes with activation by wild-type Tp53, resistance to apoptosis, failure of G1 arrest, decreased genomic stability, promotes tumorigenesis, proliferation, migration, invasion, and stability, and additionally confers a gain of function to Tp53, resulting in aberrant activation of gene transcription and enhanced cell migration (PMID: 10713666, PMID: 22114072, PMID: 19881536, PMID: 14743206, PMID: 31395785, PMID: 37030635). |
Associated Drug Resistance | |
Category Variants Paths |
TP53 mutant TP53 exon5 TP53 R175X TP53 R175H TP53 mutant TP53 inact mut TP53 R175H |
Transcript | NM_000546.6 |
gDNA | chr17:g.7675088C>T |
cDNA | c.524G>A |
Protein | p.R175H |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001126113.2 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001407266.1 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001407262.1 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_000546 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001126114 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001407264.1 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001126112 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_000546.5 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001407268.1 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001126113 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001126114.2 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001126112.2 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001407270.1 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_000546.6 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001126113.3 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001126112.3 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
NM_001126114.3 | chr17:g.7675088C>T | c.524G>A | p.R175H | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
TP53 R175H | ovarian clear cell adenocarcinoma | decreased response | DS-7423 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring TP53 R175H demonstrated reduced sensitivity to DS-7423 in culture (PMID: 24504419). | 24504419 |
TP53 R175H | breast cancer | sensitive | Ganetespib | Preclinical - Cell culture | Actionable | In a preclinical study, Ganetespib inhibited growth of human breast cancer cells harboring TP53 R175H in culture (PMID: 26009011). | 26009011 |
TP53 R175H | lung non-small cell carcinoma | resistant | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 R175H were resistant to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
TP53 R175H | colorectal cancer | sensitive | NSC59984 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with NSC59984 resulted in increased degradation of mutant Tp53 and cell death in a colorectal cancer cell line harboring TP53 R175H in culture (PMID: 26294215). | 26294215 |
TP53 R175H | breast cancer | sensitive | NSC319726 | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells harboring TP53 R175H demonstrated increased sensitivity to NSC319726 in culture (PMID: 22624712). | 22624712 |
TP53 R175H | ovarian cancer | sensitive | NSC319726 | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian cancer cells harboring TP53 R175H demonstrated increased sensitivity to NSC319726-induced growth inhibition in culture and in cell line xenograft models (PMID: 22624712). | 22624712 |
TP53 R175H | head and neck cancer | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, ReACp53 induced cell death and decreased proliferation of head and neck carcinoma cells harboring TP53 R175H in culture (PMID: 26748848). | 26748848 |
TP53 R175H | Advanced Solid Tumor | sensitive | ReACp53 | Preclinical | Actionable | In a preclinical study, treatment with ReACp53 induced cell death in primary human uterine fibroblasts expressing TP53 R175H in culture (PMID: 26748848). | 26748848 |
TP53 R175H | Advanced Solid Tumor | sensitive | Alvespimycin + Vorinostat | Preclinical | Actionable | In a preclinical study, Alvespimycin (17-DMAG) and Zolinza (vorinostat) extended survival by 59% in mice with tumors expressing Tp53 R172H (which corresponds to R175H in the human Tp53 protein) (PMID: 26009011). | 26009011 |
TP53 R175H | lung non-small cell carcinoma | sensitive | SLMP53-2 | Preclinical - Cell culture | Actionable | In a preclinical study, SLMP53-2 inhibited growth of a non-small cell lung carcinoma cell line expressing TP53 R175H in culture (PMID: 31405179). | 31405179 |
TP53 R175H | high grade glioma | sensitive | AZ32 + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in malignant glioma cells harboring TP53 R175H in culture, resulting in a greater decrease in cell survival and increased mitotic failure compared to radiation treatment alone (PMID: 29769307). | 29769307 |