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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 |
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 |
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 |