Gene Variant Detail

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Gene NRAS
Variant Q61L
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions NRAS Q61L is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61L confers a loss of function on Nras protein as indicated by increase Erk and Mek phosphorylation, and activation of Ck2alpha in cell culture (PMID: 27251789).
Associated Drug Resistance

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Transcript NM_002524
gDNA chr1:g.114713908T>A
cDNA c.182A>T
Protein p.Q61L
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524 chr1:g.114713908T>A c.182A>T p.Q61L RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS Q61L acute myeloid leukemia no benefit PD-0325901 + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, addition of Nexavar (sorafenib) to PD-0325901 treatment did not demonstrate increased sensitivity compared to PD-0325901 alone in an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 28923853). 28923853
NRAS Q61L melanoma resistant PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 did not inhibit growth of melanoma cells harboring NRAS Q61L in culture or in cell line xenograft models (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma sensitive CCT196969 Preclinical - Cell line xenograft Actionable In a preclinical study, CCT196969 inhibited MEK and ERK activation and growth of a melanoma cell line harboring NRAS Q61L in culture, and inhibited tumor growth in a NRAS Q61L-mutant melanoma cell line xenograft model (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring NRAS Q61L in culture (PMID: 26343583). 26343583
NRAS Q61L melanoma sensitive CCT241161 Preclinical - Cell line xenograft Actionable In a preclinical study, CCT241161 inhibited MEK and ERK activation and growth of a melanoma cell line harboring NRAS Q61L in culture, and inhibited tumor growth in a NRAS Q61L-mutant melanoma cell line xenograft model (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cells harboring NRAS Q61L were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
NRAS Q61L melanoma sensitive RAF709 Preclinical - Cell culture Actionable In a preclinical study, RAF709 inhibited Erk signaling and proliferation of melanoma cells harboring NRAS Q61L in culture (PMID: 29343524). 29343524
NRAS Q61L melanoma decreased response LY3009120 Preclinical Actionable In a preclinical study, LY3009120 modestly inhibited soft agar growth of human melanoma cancer cells harboring NRAS Q61L in culture (PMID: 26343583). 26343583
NRAS Q61L acute myeloid leukemia predicted - sensitive PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, PD-0325901 treatment induced apoptosis and inhibited proliferation of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 28923853). 28923853
NRAS Q61L melanoma sensitive Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). 23414587
NRAS Q61L NRAS mut melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS Q61L NRAS mut melanoma predicted - resistant Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated resistance to the combination treatment with Mekinist (trametinib) and Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
NRAS Q61L NRAS mut melanoma decreased response Palbociclib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated a decreased response to treatment with Ibrance (palbociclib) in culture when compared to control (PMID: 30819666). 30819666