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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 |
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 |
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 |