Gene Variant Detail

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Gene NRAS
Variant Q61L
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions NRAS Q61L is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61L results in increase Erk and Mek phosphorylation, and activation of Ck2alpha in cell culture (PMID: 27251789), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS Q61L (PMID: 23487764) and KRAS Q61L (PMID: 26037647).
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS act mut NRAS Q61L

NRAS mutant NRAS exon3 NRAS Q61X NRAS Q61L

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Transcript NM_002524.5
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_002524.5 chr1:g.114713908T>A c.182A>T p.Q61L RefSeq GRCh38/hg38
NM_002524.4 chr1:g.114713908T>A c.182A>T p.Q61L RefSeq GRCh38/hg38
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 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
BRAF G534D NRAS Q61L melanoma resistant Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, expression of BRAF G534D in a melanoma cell line harboring NRAS Q61L conferred resistance to treatment with Belvarafenib (HM95573) in culture (PMID: 33953400). 33953400
BRAF V600E NRAS Q61L melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing NRAS Q61L demonstrated resistance to Zelboraf (vemurafenib) in culture (PMID: 28986383). 28986383
NRAS Q61L PIK3CA E545K melanoma predicted - resistant Binimetinib + Ribociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring NRAS Q61L and expressing PIK3CA E545K was resistant to combination treatment with Mektovi (binimetinib) and Kisqali (ribociclib) in culture (PMID: 29496665). 29496665
NRAS Q61L PIK3CA E545K melanoma predicted - resistant Ribociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring NRAS Q61L and expressing PIK3CA E545K was resistant to treatment with Kisqali (ribociclib) in culture (PMID: 29496665). 29496665
NRAS Q61L PIK3CA E545K melanoma predicted - resistant Binimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring NRAS Q61L and expressing PIK3CA E545K was resistant to treatment with Mektovi (binimetinib) in culture (PMID: 29496665). 29496665
NRAS Q61L PIK3CA E545K melanoma predicted - sensitive Binimetinib + PF-4708671 + Ribociclib Preclinical - Cell culture Actionable In a preclinical study, the addition of PF-4708671 resensitized a melanoma cell line harboring NRAS Q61L and expressing PIK3CA E545K to combination treatment with Mektovi (binimetinib) and Kisqali (ribociclib) in culture, resulting in inhibition of cell growth (PMID: 29496665). 29496665
NRAS Q61L PIK3CA E545K melanoma predicted - sensitive Binimetinib + Ribociclib + Sirolimus Preclinical - Cell culture Actionable In a preclinical study, the addition of Sirolimus (rapamycin) resensitized a melanoma cell line harboring NRAS Q61L and expressing PIK3CA E545K to combination treatment with Mektovi (binimetinib) and Kisqali (ribociclib) in culture, resulting in inhibition of cell growth (PMID: 29496665). 29496665