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Gene NRAS
Variant G13D
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions NRAS G13D is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13D confers a loss of function on Nras protein as indicated by increased GTP-bound Nras, which leads to activation of downstream pathway signaling in cell culture (PMID: 17517660).
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS act mut NRAS G13D

NRAS mutant NRAS exon2 NRAS G13X NRAS G13D

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Transcript NM_002524.5
gDNA chr1:g.114716123C>T
cDNA c.38G>A
Protein p.G13D
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524.4 chr1:g.114716123C>T c.38G>A p.G13D RefSeq GRCh38/hg38
NM_002524 chr1:g.114716123C>T c.38G>A p.G13D RefSeq GRCh38/hg38
NM_002524.5 chr1:g.114716123C>T c.38G>A p.G13D RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS G13D melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cells harboring NRAS G13D were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
NRAS G13D B-cell acute lymphoblastic leukemia no benefit Everolimus Case Reports/Case Series Actionable In a clinical study, a pediatric patient with relapsed B-cell acute lymphoblastic leukemia harboring NRAS G13D, who also harbored SETD2 L1778fs* and an IKZF1 deletion, was treated with Afinitor (everolimus) in combination with chemotherapy and experienced persistent disease, and the patient died 6 months later (PMID: 33563661; NCT02670525). 33563661
NRAS G13D melanoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cells harboring NRAS G13D in culture (PMID: 26343583). 26343583
NRAS G13D melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring NRAS G13D in culture (PMID: 26343583). 26343583
NRAS G13D adult T-cell leukemia/lymphoma sensitive 3144 Preclinical - Cell culture Actionable In a preclinical study, 3144 inhibited growth of patient-derived T-cell acute lymphocytic leukemia cells harboring NRAS G13D in culture (PMID: 28235199). 28235199
NRAS G13D melanoma sensitive ASTX029 Preclinical - Cell culture Actionable In a preclinical study, ASTX029 treatment inhibited growth of a melanoma cell line harboring NRAS G13D in culture (PMID: 34330842). 34330842
NRAS G13D mantle cell lymphoma sensitive ERAS-007 Preclinical - Cell line xenograft Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a mantle cell lymphoma cell line harboring NRAS G13D in culture and inhibited tumor growth in xenograft models (PMID: 34337566). 34337566
NRAS G13D melanoma sensitive Lifirafenib + Trametinib Preclinical - Pdx Actionable In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) resulted in durable tumor regression compared to stabilized tumor growth when treated with either agent alone in patient-derived xenograft (PDX) models of melanoma harboring NRAS G13D (PMID: 33318037). 33318037
NRAS G13D mantle cell lymphoma sensitive Copanlisib + ERAS-007 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of ERAS-007 (ASN007) and Aliqopa (copanlisib) inhibited tumor growth in a cell line xenograft model of mantle cell lymphoma harboring NRAS G13D, and demonstrated improved efficacy over either agent alone (PMID: 34337566). 34337566
NRAS G13D rhabdomyosarcoma sensitive Ganitumab + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ganitumab (AMG-479) combination treatment resulted in tumor regression and increased progression-free survival in a patient-derived xenograft (PDX) model of rhabdomyosarcoma harboring NRAS G13D (PMID: 36322002). 36322002