Gene Variant Detail

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Gene HRAS
Variant Q61K
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions HRAS Q61K does not lie within any known functional domains of the Hras protein (UniProt.org). Q61K results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Associated Drug Resistance
Category Variants Paths

HRAS mutant HRAS act mut HRAS Q61K

HRAS mutant HRAS Q61X HRAS Q61K

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Transcript NM_005343.4
gDNA chr11:g.533875G>T
cDNA c.181C>A
Protein p.Q61K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_176795.4 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_001130442.3 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_001130442 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_176795.5 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_176795 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_001130442.2 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_005343 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_005343.3 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38
NM_005343.4 chr11:g.533875G>T c.181C>A p.Q61K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
HRAS Q61K rhabdomyosarcoma no benefit Trametinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and viability in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture, but did not inhibit ERK signaling in cell line xenograft models and led to tumor progression (PMID: 34737198). 34737198
HRAS Q61K rhabdomyosarcoma not predictive Rigosertib Preclinical - Cell culture Actionable In a preclinical study, Rigosertib (ON01910) inhibited cell viability and induced apoptosis and cell cycle arrest in rhabdomyosarcoma cells harboring HRAS Q61K in culture, however, cells with wild-type HRAS demonstrated the same response, and mechanistically, the response was found to be due to Rigosertib (ON0190) binding to tubulin (PMID: 33158997). 33158997
HRAS Q61K rhabdomyosarcoma sensitive LY3009120 + LY3214996 Preclinical - Cell line xenograft Actionable In a preclinical study, LY3214996 and LY3009120 combination treatment synergistically induced cell cycle arrest and apoptosis in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture and induced tumor growth regression in a xenograft model (PMID: 34737198). 34737198
HRAS Q61K rhabdomyosarcoma sensitive LY3009120 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and LY3009120 combination treatment synergistically inhibited Erk phosphorylation, proliferation, and colony formation and induced cell cycle arrest and apoptosis in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture (PMID: 34737198). 34737198
HRAS Q61K rhabdomyosarcoma sensitive LY3214996 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and LY3214996 combination treatment synergistically inhibited growth and induced apoptosis and cell cycle arrest in rhabdomyosarcoma cell lines harboring HRAS Q61K in culture and induced tumor regression in a xenograft model (PMID: 34737198). 34737198
HRAS Q61K rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) synergistically inhibited growth of rhabdomyosarcoma cell lines harboring HRAS Q61K in culture, and resulted in tumor regression and increased survival compared to either treatment alone in a cell line xenograft model (PMID: 36322002). 36322002