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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 |
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_176795.4 | chr11:g.534288C>T | c.35G>A | p.G12D | RefSeq | GRCh38/hg38 |
NM_176795.5 | 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 | 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_001130442.3 | 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_005343.4 | 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 |
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 | 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 |
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 |