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Gene | NRAS |
Variant | Q61R |
Impact List | missense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | NRAS Q61R is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61R results in increased GTP-bound Nras, which leads to activation of Mapk signaling and cell transformation in culture (PMID: 16818621, PMID: 34117033), and is predicted to lead to a loss of GTPase activity based on the effect of HRAS Q61R (PMID: 3510078). |
Associated Drug Resistance | |
Category Variants Paths |
NRAS mutant NRAS act mut NRAS Q61R NRAS mutant NRAS exon3 NRAS Q61X NRAS Q61R |
Transcript | NM_002524.5 |
gDNA | chr1:g.114713908T>C |
cDNA | c.182A>G |
Protein | p.Q61R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002524.4 | chr1:g.114713908T>C | c.182A>G | p.Q61R | RefSeq | GRCh38/hg38 |
NM_002524 | chr1:g.114713908T>C | c.182A>G | p.Q61R | RefSeq | GRCh38/hg38 |
NM_002524.5 | chr1:g.114713908T>C | c.182A>G | p.Q61R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R | melanoma | predicted - resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistance-associated mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 |
KIT D816V NRAS Q61R | melanoma | no benefit | Pembrolizumab + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring KIT D816V and NRAS Q61R demonstrated progressive disease when treated with a combination of Mekinist (trametinib) and Keytruda (pembrolizumab) (PMID: 28514312). | 28514312 |
ATM mut NRAS Q61R | melanoma | predicted - sensitive | Binimetinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring an ATM mutation and NRAS Q61R demonstrated a partial response and 16 month progression free survival when treated with Binimetinib (MEK162) (PMID: 28514312). | 28514312 |
BRAF V600E MAP2K1 Q56P NRAS Q61R | melanoma | sensitive | AZD0364 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD0364 (ATG-017) decreased phosphorylation of Erk target genes and increased expression of apoptosis markers in melanoma cells harboring BRAF V600E, MAP2K1 Q56P, and NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 33273059). | 33273059 |
BRAF N581S NRAS Q61R | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease stability with shrinkage of metastatic lesions in a melanoma patient harboring BRAF N581S and NRAS Q61R (PMID: 36217799). | 36217799 |
FLT3 exon 14 ins FLT3 D835X NRAS Q61R | acute myeloid leukemia | predicted - resistant | Gilteritinib | Case Reports/Case Series | Actionable | In a clinical study, a patient with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and was found to have acquired NRAS Q61R in addition to WT1 L378Pfs*6 (PMID: 31088841). | 31088841 |
BRAF V600E NRAS Q61R | melanoma | sensitive | Encorafenib + Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, treatment with the combination of Talzenna (talazoparib) and Braftovi (encorafenib) synergistically inhibited viability of patient-derived melanoma spheroids harboring BRAF V600E and NRAS Q61R in culture (PMID: 37729428). | 37729428 |
BRAF V600E NRAS Q61R | melanoma | sensitive | Binimetinib + Encorafenib + Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, treatment with the combination of Talzenna (talazoparib) Braftovi (encorafenib), and Mektovi (binimetinib) synergistically inhibited viability of patient-derived melanoma spheroids harboring BRAF V600E and NRAS Q61R in culture (PMID: 37729428). | 37729428 |
BRAF V600E NRAS Q61R | melanoma | resistant | Dabrafenib | Preclinical - Pdx | Actionable | In a preclinical study, a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R was resistant to treatment with Tafinlar (dabrafenib) (PMID: 37729428). | 37729428 |
BRAF V600E NRAS Q61R | melanoma | resistant | Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R was resistant to treatment with Mekinist (trametinib) (PMID: 37729428). | 37729428 |
BRAF V600E NRAS Q61R | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) moderately inhibited tumor growth in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R (PMID: 37729428). | 37729428 |
BRAF V600E NRAS Q61R | melanoma | sensitive | Dabrafenib + Talazoparib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with the combination of Talzenna (talazoparib), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited tumor growth and improved survival compared to controls in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R (PMID: 37729428). | 37729428 |
BRAF V600E NRAS Q61R | melanoma | sensitive | Talazoparib | Preclinical - Pdx | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited tumor growth and led to improved survival compared to controls in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R (PMID: 37729428). | 37729428 |