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Gene | NRAS |
Variant | G12C |
Impact List | missense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | NRAS G12C is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12C has not been characterized, but can be predicted to confer a loss of function to the Nras protein based on the effects of HRAS G12C and KRAS G12C, which result in a loss of response to GTPase-activating proteins, and transformation of cultured cells (PMID: 26037647, PMID: 6092966). |
Associated Drug Resistance | |
Category Variants Paths |
NRAS mutant NRAS act mut NRAS G12C NRAS mutant NRAS exon2 NRAS G12X NRAS G12C |
Transcript | NM_002524.5 |
gDNA | chr1:g.114716127C>A |
cDNA | c.34G>T |
Protein | p.G12C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002524.4 | chr1:g.114716127C>A | c.34G>T | p.G12C | RefSeq | GRCh38/hg38 |
NM_002524.5 | chr1:g.114716127C>A | c.34G>T | p.G12C | RefSeq | GRCh38/hg38 |
NM_002524 | chr1:g.114716127C>A | c.34G>T | p.G12C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | resistant | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C demonstrated resistance to treatment with FF-10101 in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and expressing NRAS G12C were resistant to Vanflyta (quizartinib) in culture (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | resistant | Gilteritinib | Preclinical - Biochemical | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and expressing NRAS G12C were resistant to Xospata (gilteritinib) in culture (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and NRAS G12C were resistant to Xospata (gilteritinib) as demonstrated by increased cell growth and RAS/MAPK pathway activation in culture (PMID: 31088841). | 31088841 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | predicted - sensitive | FF-10101 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of FF-10101 and Mekinist (trametinib) resulted in decreased viability of acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C compared to treatment with FF-10101 alone in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | sensitive | Gilteritinib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Xospata (gilteritinib) and Mekinist (trametinib) inhibited cell growth in acute myeloid leukemia cells harboring FLT3-ITD and NRAS G12C in culture (PMID: 31088841). | 31088841 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | sensitive | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 inhibited viability in an acute myeloid leukemia cell line harboring FLT3 ITD and NRAS G12C in culture (PMID: 37992684). | 37992684 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | sensitive | Gilteritinib + RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of RMC-4550 and Xospata (gilteritinib) inhibited viability in an acute myeloid leukemia cell line harboring FLT3 ITD and NRAS G12C in culture (PMID: 37992684). | 37992684 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | sensitive | RMC-4550 + Venetoclax | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of RMC-4550 and Venclexta (venetoclax) synergistically inhibited viability and induced apoptosis in an acute myeloid leukemia cell line harboring FLT3 ITD and NRAS G12C in culture, and reduced tumor burden and improved survival in a cell line xenograft model (PMID: 37992684). | 37992684 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | decreased response | Foretinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and expressing NRAS G12C were less sensitive to Foretinib (GSK1363089) in culture (PMID: 38231480). | 38231480 |