NRAS G12X
Gene Variant Detail

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Gene NRAS
Variant G12X
Impact List missense
Protein Effect unknown
Gene Variant Descriptions NRAS G12X indicates any NRAS missense mutation that results in replacement of the glycine (G) at amino acid 12 by a different amino acid. NRAS G12 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 exon2 NRAS G12X

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Transcript NM_002524.5
gDNA chr1:g.114716125_114716127
cDNA c.34_36
Protein p.G12
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524.5 chr1:g.114716125_114716127 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_002524 chr1:g.114716125_114716127 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_002524.4 chr1:g.114716125_114716127 c.34_36 p.G12 RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS G12X myelodysplastic syndrome not applicable N/A Guideline Prognostic NRAS G12X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
NRAS G12X colorectal cancer resistant Cetuximab FDA contraindicated Actionable Erbitux (cetuximab) treatment of colorectal cancer patients with NRAS exon 2, codon 12 mutations is contraindicated (FDA.gov). detail...
NRAS G12X colorectal cancer resistant Panitumumab FDA contraindicated Actionable Vectibix (panitumumab) treatment of colorectal cancer patients with NRAS exon 2, codon 12 mutations is contraindicated (FDA.gov). detail...
NRAS G12X Advanced Solid Tumor no benefit Binimetinib Phase II Actionable In a Phase II trial (MATCH), Mektovi (binimetinib) treatment resulted in an objective response rate of 2.1% (1/47) that was deemed nonpromising in patients with advanced solid tumors harboring NRAS mutations at codon 12 (n=17), 13 (n=8), or 61 (n=22), with a 6-month progression-free survival (PFS) of 29.2%, a median PFS of 3.5 months, and a median overall survival of 10.5 months (PMID: 33637626; NCT02465060). 33637626
NRAS G12X 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 13.3% in patients with an NRAS G12 mutation (n=15) (PMID: 38479118; NCT05217303). 38479118