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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 |
Transcript | NM_005343.3 |
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_005343.3 | 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_001130442 | 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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 | 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 |
BRAF G466E HRAS Q61K | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF G466E and HRAS Q61K in culture (PMID: 28783719). | 28783719 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
HRAS Q61K | loss of function | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor PIK3CB inhibitor PIK3CD inhibitor PIK3CG inhibitor RAS Inhibitor (Pan) |
BRAF G466E HRAS Q61K |