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Gene HRAS
Variant G12D
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions HRAS G12D does not lie within any known functional domains of the Hras protein (UniProt.org). G12D results in decreased Hras GTPase activity, loss of sensitivity to GTPase-activating proteins, thus leads to transformation of cells in culture (PMID: 24224811, PMID: 6092966).
Associated Drug Resistance
Category Variants Paths

HRAS mutant HRAS act mut HRAS G12D

HRAS mutant HRAS G12X HRAS G12D

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Transcript NM_005343.4
gDNA chr11:g.534288C>T
cDNA c.35G>A
Protein p.G12D
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_176795.5 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_001130442 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_005343.3 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_001130442.2 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_005343.4 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_005343 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_176795.4 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_001130442.3 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38
NM_176795 chr11:g.534288C>T c.35G>A p.G12D RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
HRAS G12D 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 head and neck squamous cell carcinoma cell lines harboring HRAS G12D in culture (PMID: 35247914). 35247914
HRAS G12D head and neck squamous cell carcinoma 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 G12D to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and increased apoptosis in culture (PMID: 35247914). 35247914
HRAS G12D head and neck squamous cell carcinoma sensitive SCH772984 + Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, the addition of SCH772984 sensitized head and neck squamous cell carcinoma cell lines harboring HRAS G12D to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and increased apoptosis in culture (PMID: 35247914). 35247914
HRAS G12D head and neck squamous cell carcinoma sensitive Tipifarnib + Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, combination treatment with Ulixertinib (BVD-523) and Zarnestra (tipifarnib) resulted in a synergistic effect, with enhanced apoptosis in a head and neck squamous cell carcinoma cell lines harboring HRAS G12D in culture (PMID: 35247914). 35247914
HRAS G12D Advanced Solid Tumor no benefit MRTX-1133 Preclinical - Cell culture Actionable In a preclinical study, cultured cells expressing HRAS G12D were not sensitive to treatment with MRTX1133 (PMID: 37339170). 37339170