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Gene | HRAS |
Variant | G12V |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | HRAS G12V does not lie within any known functional domains of the Hras protein (UniProt.org). G12V results in decreased Hras GTPase activity, loss of response to GTPase-activating proteins, leading to activation of downstream signaling pathways, and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 6330729). |
Associated Drug Resistance |
Transcript | NM_005343.3 |
gDNA | chr11:g.534288C>A |
cDNA | c.35G>T |
Protein | p.G12V |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_005343 | chr11:g.534288C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
NM_176795.4 | chr11:g.534288C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
NM_176795 | chr11:g.534288C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
NM_001130442 | chr11:g.534288C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
NM_001130442.2 | chr11:g.534288C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
NM_005343.3 | chr11:g.534288C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
HRAS G12V | Advanced Solid Tumor | sensitive | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing HRAS G12V demonstrated sensitivity to growth inhibition by Binimetinib (MEK162) in culture (PMID: 26544513). | 26544513 |
HRAS G12V | Advanced Solid Tumor | sensitive | Rigosertib Sodium | Preclinical - Cell culture | Actionable | In a preclinical study, Rigosertib (ON 01910.Na) inhibited oncogenic transformation in fibroblast cells over-expressing HRAS G12V in culture (PMID: 27104980). | 27104980 |
HRAS G12V | urinary bladder cancer | sensitive | Everolimus + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Selumetinib (AZD6244) and Afinitor (everolimus) reduced phosphorylation of ERK and S6 and worked synergistically to inhibit growth of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 26544513). | 26544513 |
HRAS G12V | melanoma | sensitive | CI-1040 | Preclinical | Actionable | In a preclinical study CI-1040 (PD-184352) inhibited melanoma progression in a transgenic zebrafish model of melanoma expressing HRAS G12V (PMID: 26267534). | 26267534 |
HRAS G12V | Advanced Solid Tumor | sensitive | Pz-1 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Pz-1 reduced tumor growth in xenograft models of transformed cells over expressing HRAS G12V in a dose-dependent manner (PMID: 26126987). | 26126987 |
HRAS G12V | Advanced Solid Tumor | sensitive | WM-8014 | Preclinical | Actionable | In a preclinical study, WM-8014 inhibited proliferation of a transformed mouse cell line expressing HRAS G12V in culture, and inhibited proliferation and induced senescence in a transgenic zebrafish model (PMID: 30069049). | 30069049 |
HRAS G12V | Advanced Solid Tumor | predicted - sensitive | SR9011 | Preclinical - Cell culture | Actionable | In a preclinical study, SR9011 treatment resulted in apoptosis in HRAS G12V-induced senescent firbroblast cells in culture (PMID: 29320480). | 29320480 |
HRAS G12V | Advanced Solid Tumor | resistant | Panitumumab | Preclinical | Actionable | In a preclinical study, tumor cells expressing HRAS G12V demonstrated resistance to treatment with Vectibix (panitumumab) (PMID: 22797062). | 22797062 |
HRAS G12V | Advanced Solid Tumor | sensitive | Binimetinib + Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Afinitor (everolimus) worked synergistically to inhibit growth of transformed cells expressing HRAS G12V in culture (PMID: 26544513). | 26544513 |
HRAS G12V | Advanced Solid Tumor | sensitive | Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing HRAS G12V demonstrated sensitivity to growth inhibition by Afinitor (everolimus) in culture (PMID: 26544513). | 26544513 |
HRAS G12V | high grade glioma | sensitive | SF1126 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SF1126 inhibited Akt activation, proliferation, and migration of transgenic mouse glioma cells expressing HRAS G12V in culture, and suppressed tumor growth in xenograft models (PMID: 25425962). | 25425962 |
HRAS G12V | urinary bladder cancer | sensitive | Binimetinib + Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Afinitor (everolimus) reduced phosphorylation of ERK and S6 and worked synergistically to inhibit growth of a bladder cell line harboring HRAS G12V in culture (PMID: 26544513). | 26544513 |
HRAS G12V | Advanced Solid Tumor | predicted - sensitive | SR9009 | Preclinical - Cell culture | Actionable | In a preclinical study, SR9009 treatment resulted in apoptosis in HRAS G12V-induced senescent firbroblast cells in culture (PMID: 29320480). | 29320480 |
HRAS G12V | Advanced Solid Tumor | resistant | Cetuximab | Preclinical | Actionable | In a preclinical study, tumor cells expressing HRAS G12V demonstrated resistance to treatment with Erbitux (cetuximab) (PMID: 22797062). | 22797062 |
FGFR3 dec exp FGFR3 wild-type HRAS G12V | transitional cell carcinoma | resistant | AZD4547 | Preclinical | Actionable | In a preclinical study, urothelial cancer cells with low expression of wild-type FGFR3 that harbored HRAS G12V demonstrated resistance to AZD4547 in culture (PMID: 22869148). | 22869148 |
FGFR3 dec exp FGFR3 wild-type HRAS G12V | transitional cell carcinoma | decreased response | AZ8010 | Preclinical | Actionable | In a preclinical study, urothelial cancer cells with low expression of wild-type FGFR3 that harbored HRAS G12V demonstrated resistance to AZ8010 in culture (PMID: 22869148). | 22869148 |
FGFR3 dec exp FGFR3 wild-type HRAS G12V | transitional cell carcinoma | resistant | PD173074 | Preclinical | Actionable | In a preclinical study, urothelial cancer cells with low expression of wild-type FGFR3 that harbored HRAS G12V demonstrated resistance to PD173074 in culture (PMID: 22869148). | 22869148 |
HRAS G12V HRAS R135A | Advanced Solid Tumor | resistant | NS1 | Preclinical | Actionable | In a preclinical study, introducing HRAS R135A mutation in transformed cells expressing HRAS G12V resulted in reduced binding of Hras to NS1, leading to resistance to Mapk pathway inhibition in cell culture (PMID: 27820802). | 27820802 |
HRAS G12V HRAS R135K | Advanced Solid Tumor | resistant | NS1 | Preclinical | Actionable | In a preclinical study, introducing HRAS R135K mutation in transformed cells expressing HRAS G12V resulted in reduced binding of Hras to NS1, leading to resistance to Mapk pathway inhibition in cell culture (PMID: 27820802). | 27820802 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
HRAS G12V | loss of function | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor PIK3CB inhibitor PIK3CD inhibitor PIK3CG inhibitor RAS Inhibitor (Pan) |
FGFR3 dec exp FGFR3 wild-type HRAS G12V | ||
HRAS G12V HRAS R135A | ||
HRAS G12V HRAS R135K |