Gene Variant Detail

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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
Category Variants Paths

HRAS mutant HRAS G12X HRAS G12V

HRAS mutant HRAS act mut HRAS G12V

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Transcript NM_005343.4
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_001130442.3 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
NM_005343.4 chr11:g.534288C>A c.35G>T p.G12V RefSeq GRCh38/hg38
NM_005343 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_001130442.2 chr11:g.534288C>A c.35G>T p.G12V RefSeq GRCh38/hg38
NM_176795.5 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_176795.4 chr11:g.534288C>A c.35G>T p.G12V RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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
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 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 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 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 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 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 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 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 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 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 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 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 urinary bladder cancer sensitive ERAS-007 Preclinical - Cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 34337566). 34337566
HRAS G12V urinary bladder cancer sensitive RAF265 Preclinical - Cell culture Actionable In a preclinical study, RAF265 treatment decreased viability and colony formation of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 34554931). 34554931
HRAS G12V urinary bladder cancer sensitive RAF265 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, RAF265 and Mekinist (trametinib) combination treatment inhibited colony formation compared to RAF265 alone in cultured cells harboring HRAS G12V (PMID: 34554931). 34554931
HRAS G12V urinary bladder cancer sensitive LXH 254 Preclinical - Cell culture Actionable In a preclinical study, LXH 254 treatment decreased viability of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 34554931). 34554931
HRAS G12V head and neck squamous cell carcinoma sensitive Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, Zarnestra (tipifarnib) treatment led to decreased cell viability and inhibition of clonogenic and anchorage-independent growth in a head and neck squamous cell carcinoma cell line harboring HRAS G12V in culture (PMID: 35247914). 35247914
HRAS G12V head and neck squamous cell carcinoma predicted - sensitive Alpelisib + Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, the addition of Piqray (alpelisib) sensitized head and neck squamous cell carcinoma cell lines harboring HRAS G12V to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and apoptosis in culture (PMID: 35247914). 35247914