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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

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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

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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