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Gene | HRAS |
Variant | G13R |
Impact List | missense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | HRAS G13R is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13R results in activation of Mapk and Pi3k signaling, increased cell proliferation in culture (PMID: 22683711), and is predicted to lead to a loss of Hras protein function based on the effects of other HRAS G13 mutations. |
Associated Drug Resistance | |
Category Variants Paths |
HRAS mutant HRAS act mut HRAS G13R HRAS mutant HRAS G13X HRAS G13R |
Transcript | NM_005343.4 |
gDNA | chr11:g.534286C>G |
cDNA | c.37G>C |
Protein | p.G13R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001130442.3 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
NM_005343.3 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
NM_176795.4 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
NM_005343.4 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
NM_001130442.2 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
NM_176795.5 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
NM_176795 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
NM_005343 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
NM_001130442 | chr11:g.534286C>G | c.37G>C | p.G13R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
HRAS G13R | thyroid cancer | sensitive | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an anaplastic thyroid cancer cell line harboring HRAS G13R (PMID: 21289267). | 21289267 |
HRAS G13R | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS G13R was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). | 32727882 |
HRAS G13R | renal pelvis transitional cell carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with renal pelvis transitional cell carcinoma harboring HRAS G13R achieved a partial response (PMID: 32636318; NCT02535650). | 32636318 |
HRAS G13R | thyroid cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
HRAS G13R | thyroid cancer | sensitive | Dasatinib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited growth and induced apoptosis in a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
HRAS G13R | thyroid cancer | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited growth of a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
HRAS G13R | thyroid cancer | sensitive | Dasatinib + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and Koselugo (selumetinib) synergistically inhibited growth and induced apoptosis in a thyroid cancer cell line harboring HRAS G13R in culture (PMID: 27222538). | 27222538 |
HRAS G13R | rhabdomyosarcoma | sensitive | Ganitumab + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) combination treatment resulted in tumor regression and increased progression-free survival in a patient-derived xenograft (PDX) model of rhabdomyosarcoma harboring HRAS G13R (PMID: 36322002). | 36322002 |
HRAS G13R | Advanced Solid Tumor | sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of HRAS G13R in an HRAS-null, NRAS-null, and KRAS knockout cell line conferred sensitivity to Zarnestra (tipifarnib) in culture, resulting in decreased cell viability (PMID: 39152269). | 39152269 |
HRAS G13R | Advanced Solid Tumor | sensitive | Tipifarnib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with Zarnestra (tipifarnib) and Mekinist (trametinib) decreased viability of HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R compared to Zarnestra (tipifarnib) treatment alone in culture (PMID: 39152269). | 39152269 |