Gene Variant Detail

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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

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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_176795.5 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 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_001130442 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_176795 chr11:g.534286C>G c.37G>C p.G13R RefSeq GRCh38/hg38
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

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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