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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

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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_001126112 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_001126112.3 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_001407262.1 chr17:g.7675088C>T c.524G>A p.R175H RefSeq GRCh38/hg38
NM_001126113.2 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_001126114.3 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_001407264.1 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 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_001126114 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_001126114.2 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

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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