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|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
|Transcript||gDNA||cDNA||Protein||Source Database||Genome Build|
|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|