Gene Variant Detail

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Gene NRAS
Variant Q61H
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions NRAS Q61H is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61H results in increased GTP-bound Nras, downstream pathway activation, and increased cell proliferation in culture (PMID: 23103856), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS Q61H (PMID: 3510078) and KRAS Q61H (PMID: 20147967).
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS exon3 NRAS Q61X NRAS Q61H

NRAS mutant NRAS act mut NRAS Q61H

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Transcript NM_002524.4
gDNA chr1:g.114713907T>A
cDNA c.183A>T
Protein p.Q61H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524.4 chr1:g.114713907T>A c.183A>T p.Q61H RefSeq GRCh38/hg38
NM_002524 chr1:g.114713907T>A c.183A>T p.Q61H RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS Q61H rhabdomyosarcoma sensitive Alpelisib + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in rhabdomyosarcoma cells harboring NRAS Q61H, demonstrating cell death in culture (PMID: 29437705). 29437705
NRAS Q61H rhabdomyosarcoma not predictive Rigosertib Preclinical - Cell line xenograft Actionable In a preclinical study, Rigosertib (ON01910) inhibited cell viability and induced apoptosis and cell cycle arrest in rhabdomyosarcoma cells harboring NRAS Q61H in culture, and delayed tumor growth in cell line xenograft models, however, cells with wild-type NRAS demonstrated the same response, and mechanistically, the response was found to be due to Rigosertib (ON0190) binding to tubulin (PMID: 33158997). 33158997
NRAS Q61H 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 NRAS Q61H in culture, but did not inhibit ERK signaling in cell line xenograft models and led to tumor progression (PMID: 34737198). 34737198
NRAS Q61H 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 a rhabdomyosarcoma cell line harboring NRAS Q61H in culture (PMID: 34737198). 34737198
NRAS Q61H rhabdomyosarcoma sensitive LY3214996 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) and LY3214996 combination treatment synergistically inhibited growth and induced apoptosis and cell cycle arrest in a rhabdomyosarcoma cell line harboring NRAS Q61H in culture and delayed tumor growth in a xenograft model (PMID: 34737198). 34737198
NRAS Q61H rhabdomyosarcoma sensitive LY3009120 + LY3214996 Preclinical - Cell culture Actionable In a preclinical study, LY3214996 and LY3009120 combination treatment synergistically induced cell cycle arrest and apoptosis in rhabdomyosarcoma cell lines harboring NRAS Q61H in culture (PMID: 34737198). 34737198
NRAS Q61H mucosal melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited downstream signaling and decreased viability of a mucosal melanoma cell line harboring NRAS Q61H in culture (PMID: 29054983). 29054983
NRAS Q61H rhabdomyosarcoma predicted - sensitive Ganitumab + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Mekinist (trametinib) and Ganitumab (AMG-479) synergistically inhibited growth of a rhabdomyosarcoma cell line harboring NRAS Q61H in culture, but did not improve tumor suppression and survival compared to monotherapy in a cell line xenograft model (PMID: 36322002). 36322002