Gene Variant Detail

Gene NRAS
Variant G12D
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions NRAS G12D is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12D confers a loss of function on Nras protein as indicated by decreased intrinsic GTPase activity, reduced sensitivity to GTPase-activating proteins, leading to accumulation of GTP-bound Nras, activation of downstream signaling, and transformation of cultured cells (PMID: 19075190, PMID: 25252692).
Associated Drug Resistance

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Transcript NM_002524
gDNA chr1:g.114716126C>T
cDNA c.35G>A
Protein p.G12D
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524 chr1:g.114716126C>T c.35G>A p.G12D RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF D594G NRAS G12D melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
NRAS G12D acute myeloid leukemia sensitive Binimetinib Preclinical Actionable In a preclinical study, Binimetinib (MEK162) inhibited growth of acute myeloid leukemia cells that have been demonstrated to harbor NRAS G12D in culture and decreased disease burden in xenograft models with NRAS G12D (PMID: 24569456, PMID: 11238126). 24569456 11238126
NRAS G12D Advanced Solid Tumor sensitive N-Arachidonoyl Dopamine Preclinical - Cell culture Actionable In a preclinical study, N-Arachidonoyl Dopamine (NADA) disrupted NRAS protein membrane localization and decreased NRAS downstream signaling, and inhibited proliferation and induced cell death in transformed cells expressing NRAS G12D in culture (PMID: 27760835). 27760835
NRAS G12D acute myeloid leukemia sensitive Alpelisib + Binimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Alpelisib (BYL719) inhibited proliferation in a human acute myeloid leukemia (AML) cell line harboring NRAS G12D in culture, and decreased disease burden in xenograft models (PMID: 24569456). 24569456
BRAF V600E KRAS G13C NRAS G12D lymphatic system cancer predicted - sensitive Cobimetinib Case Reports/Case Series Actionable In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, including a complete response in a patient with Langerhans cell histiocytosis harboring BRAF V600E, KRAS G13C, and NRAS G12D (PMID: 30867592; NCT01953926). 30867592
KMT2A-MLLT1 NRAS G12D acute myeloid leukemia sensitive Dinaciclib Preclinical Actionable In a preclinical study, acute myeloid leukemia cells co-harboring KMT2A-MLLT1 and NRAS G12D demonstrated a decrease in tumor burden, reduced colony formation, and an increase in cell death when treated with Dinaciclib in both culture and mouse models (PMID: 26627013). 26627013
KMT2A-MLLT1 NRAS G12D acute myeloid leukemia predicted - sensitive AZ20 Preclinical Actionable In a preclinical study, AZ20 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). 27625305
KMT2A-MLLT1 NRAS G12D acute myeloid leukemia predicted - sensitive AZD0156 Preclinical Actionable In a preclinical study, AZD0156 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). 27625305
AKT1 E17K NRAS G12D prostate cancer sensitive BAY1125976 Preclinical - Cell line xenograft Actionable In a preclinical study, BAY1125976 inhibited proliferation of a prostate cancer cell line harboring AKT E17K and NRAS G12D in culture, and demonstrated antitumor activity in xenograft models (PMID: 27699769). 27699769