Gene Variant Detail

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Gene NRAS
Variant G13R
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions NRAS G13R is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13R results in increased MAPK/ERK pathway activation in an in vitro assay, is transforming in culture (PMID: 34117033), and can be predicted to lead to a loss of Nras protein function based on the effects of other NRAS G13 mutations.
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS exon2 NRAS G13X NRAS G13R

NRAS mutant NRAS act mut NRAS G13R

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Transcript NM_002524.4
gDNA chr1:g.114716124C>G
cDNA c.37G>C
Protein p.G13R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524.4 chr1:g.114716124C>G c.37G>C p.G13R RefSeq GRCh38/hg38
NM_002524 chr1:g.114716124C>G c.37G>C p.G13R RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF G596V NRAS G13R colorectal cancer sensitive Cetuximab + LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in a patient-derived xenograft model of colorectal cancer harboring BRAF G596V and NRAS G13R (PMID: 28611205). 28611205
BRAF V600E NRAS G13R colorectal cancer predicted - resistant Alpelisib + Cetuximab + Encorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 24 weeks to Alpelisib (BYL719), Erbitux (cetuximab), and Braftovi (encorafenib) combination treatment, NRAS G13R was identified as an acquired mutation in liver metastasis at the time of progression (PMID: 28951457). 28951457
BRAF V600E NRAS G13R colorectal cancer predicted - sensitive BGB659 + Cetuximab Preclinical - Pdx Actionable In a preclinical study, BGB659 and Erbitux (cetuximab) combination treatment resulted in sustained inhibition of Mek and Erk phosphorylation, lead to tumor regression in patient-derived xenograft models of colorectal cancer harboring BRAF V600E and NRAS G13R (PMID: 28951457). 28951457
NRAS G13R PIK3CA E545K melanoma predicted - resistant Binimetinib + Ribociclib Case Reports/Case Series Actionable In a Phase Ib/II trial, a patient with melanoma harboring NRAS G13R experienced disease progression on combination treatment with Mektovi (binimetinib) and Kisqali (ribociclib), likely due to the acquisition of PIK3CA E545K (PMID: 29496665; NCT01781572). 29496665
NRAS G13R PIK3CA H1047R rhabdomyosarcoma resistant Ganitumab + Trametinib Preclinical - Pdx Actionable In a preclinical study, a patient-derived xenograft (PDX) model of rhabdomyosarcoma harboring NRAS G13R and PIK3CA H1047R was resistant to the Mekinist (trametinib) and Ganitumab (AMG-479) combination treatment (PMID: 36322002). 36322002
FLT3 exon 14 ins FLT3 D835X NRAS G13R acute myeloid leukemia predicted - resistant Gilteritinib Case Reports/Case Series Actionable In a clinical study, two patients with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and were found to have acquired NRAS G13R (PMID: 31088841). 31088841
FLT3 exon 14 ins FLT3 D835X NRAS G13C NRAS G13R acute myeloid leukemia predicted - resistant Gilteritinib Case Reports/Case Series Actionable In a clinical study, a patient with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and was found to have acquired NRAS G13C and G13R (PMID: 31088841). 31088841