Gene Variant Detail

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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

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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 chr1:g.114713908T>C c.182A>G p.Q61R RefSeq GRCh38/hg38
NM_002524.4 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

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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