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Gene | HRAS |
Variant | G13R |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | HRAS G13R is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13R confers a loss of function on Hras protein as indicated by activation of Mapk and Pi3k signaling, increased cell proliferation in culture (PMID: 22683711). |
Associated Drug Resistance |
Transcript | NM_005343.3 |
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_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 |
NM_001130442.2 | 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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 gland 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 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
HRAS G13R | loss of function | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor PIK3CB inhibitor PIK3CD inhibitor PIK3CG inhibitor RAS Inhibitor (Pan) |