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Gene NRAS
Variant Q61X
Impact List missense
Protein Effect unknown
Gene Variant Descriptions NRAS Q61X indicates any NRAS missense mutation that results in replacement of the glutamine (Q) at amino acid 61 by a different amino acid. NRAS Q61 mutations are hotspot mutations that often result in a loss of Nras GTPase activity and activation of downstream pathways (PMID: 27664710, PMID: 28666118, PMID: 22589270, PMID: 26985062).
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS exon3 NRAS Q61X

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Transcript NM_002524.5
gDNA chr1:g.114713907_114713909
cDNA c.181_183
Protein p.Q61
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524 chr1:g.114713907_114713909 c.181_183 p.Q61 RefSeq GRCh38/hg38
NM_002524.5 chr1:g.114713907_114713909 c.181_183 p.Q61 RefSeq GRCh38/hg38
NM_002524.4 chr1:g.114713907_114713909 c.181_183 p.Q61 RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS Q61X melanoma sensitive Binimetinib + Ribociclib Phase Ib/II Actionable In a Phase Ib/II trial, Kisqali (ribociclib) plus Mektovi (binimetinib) was well tolerated in NRAS-mutant melanoma patients and resulted in an overall response rate (ORR) of 19.5% (8/41; all PR), disease control rate of 70.7% (29/41), median duration of response of 10.3 months, median progression-free survival of 3.7 months, and median overall survival (OS) of 11.3 months in the phase II cohort, and a response rate of 22.9% (16/70) in patients with an NRAS Q61 mutation overall (PMID: 35294522; NCT01781572). 35294522
NRAS Q61X colorectal cancer resistant Cetuximab FDA contraindicated Actionable Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 3, codon 61 mutations is contraindicated (FDA.gov). detail...
NRAS Q61X colorectal cancer unknown Binimetinib Phase II Actionable In a Phase II trial (MATCH), Mektovi (binimetinib) treatment did not demonstrate promising efficacy in patients with advanced solid tumors harboring NRAS mutations at codon 12 (n=17), 13 (n=8), or 61 (n=22), however, colorectal cancer patients harboring NRAS Q61 mutations (n=8) achieved longer overall survival (HR 0.34, p=0.03) and progression-free survival (HR 0.23, p=0.007) compared to those harboring mutations at G12 or G13 (n=16) (PMID: 33637626; NCT02465060). 33637626
NRAS Q61X Advanced Solid Tumor unknown Binimetinib Phase II Actionable In a Phase II trial (MATCH), Mektovi (binimetinib) therapy led to a nonpromising objective response rate of 2.1% (1/47) in patients (pts) with advanced solid tumors harboring NRAS G12/13 or Q61 mutations, Q61-mutant pts achieved longer overall survival (13.1 vs 5.5 mo, p=0.04) and progression-free survival (5.8 vs 1.8 mo, p=0.006) compared to G12/13-mutant pts examining all tumor types, but not when colorectal caner was excluded (HR 0.84, p=0.70; HR 0.67, p=0.4, respectively) (PMID: 33637626; NCT02465060). 33637626
NRAS Q61X colorectal cancer resistant Panitumumab FDA contraindicated Actionable Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 3, codon 61 mutations is contraindicated (FDA.gov). detail...
NRAS Q61X myelodysplastic syndrome not applicable N/A Guideline Prognostic NRAS Q61X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
NRAS Q61X melanoma predicted - sensitive Tunlametinib Phase II Actionable In a Phase II trial, Tunlametinib (HL-085) treatment resulted in a confirmed objective response rate (ORR) of 35.8% (34/95, all partial responses), a median progression-free survival of 4.2 months, disease control rate of 72.6% (69/95), median duration of response of 6.1 months, and median overall survival of 13.7 months in Chinese patients with advanced melanoma harboring NRAS mutations, with an ORR of 41.3% in patients with an NRAS Q61 mutation (n=75) (PMID: 38479118; NCT05217303). 38479118