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Gene | NRAS |
Variant | G12V |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | NRAS G12V is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12V confers a loss of function on Nras protein as indicated by accumulation of GTP-bound Nras, loss of GTPase-activating protein sensitivity, leading to increased downstream pathway activation in cell culture (PMID: 19966803). |
Associated Drug Resistance | |
Category Variants Paths |
NRAS mutant NRAS act mut NRAS G12V NRAS mutant NRAS exon2 NRAS G12X NRAS G12V |
Transcript | NM_002524.5 |
gDNA | chr1:g.114716126C>A |
cDNA | c.35G>T |
Protein | p.G12V |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002524.4 | chr1:g.114716126C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
NM_002524 | chr1:g.114716126C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
NM_002524.5 | chr1:g.114716126C>A | c.35G>T | p.G12V | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E NRAS G12V | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). | 26267534 |
BRAF V600E NRAS G12V | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and over expressing NRAS G12V in culture (PMID: 26267534). | 26267534 |
BRAF V600E CDKN2A loss NRAS G12V | melanoma | predicted - resistant | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600E experienced progressive disease after a response to combination therapy with Zelboraf (vemurafenib) and Cotellic (cobimetinib), likely due to acquisition of NRAS G12V and a loss of one copy of CDKN2A (PMID: 34376578). | 34376578 |
BRAF V600E CDKN2A loss NRAS G12V | melanoma | predicted - sensitive | Palbociclib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Ibrance (palbociclib) and Mekinist (trametinib) led to inhibition of tumor growth in a patient-derived xenograft (PDX) model of melanoma harboring BRAF V600E, NRAS G12V, and CDKN2A copy number loss (PMID: 34376578). | 34376578 |
BRAF V600E CDKN2A loss NRAS G12V | melanoma | predicted - sensitive | Palbociclib + Ulixertinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Ibrance (palbociclib) and Ulixertinib (BVD-523) led to inhibition of tumor growth in a patient-derived xenograft (PDX) model of melanoma harboring BRAF V600E, NRAS G12V, and CDKN2A copy number loss (PMID: 34376578). | 34376578 |