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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 |
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 | chr1:g.114716125_114716127 | c.34_36 | p.G12 | RefSeq | GRCh38/hg38 |
NM_002524.5 | 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 |
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 |