Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Gene NRAS
Variant A146T
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions NRAS A146T does not lie within any known functional domains of the Nras protein (UniProt.org). A146T results in increased Nras activity likely due to increased GDP/GTP exchange rate, activation of downstream signaling, and is identified as a secondary mutation conferring resistance to Braf and Mek inhibitors in culture (PMID: 22389471, PMID: 3043178).
Associated Drug Resistance Y

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.114709583C>T
cDNA c.436G>A
Protein p.A146T
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524 chr1:g.114709583C>T c.436G>A p.A146T 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 V600E MAP2K1 P387S NRAS A146T melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma no benefit Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS A146T melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were >10-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T melanoma sensitive Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). 22389471