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 MAP2K1
Variant L115P
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions MAP2K1 L115P lies within the protein kinase domain of the Map2k1 protein (UniProt.org). L115P confers a gain of function on the kinase activity of the Map2k1 protein, as demonstrated by increased autophosphorylation (PMID: 29753091) and increased basal kinase activity (PMID: 12370306), and is also associated with decreased binding and resistance to Mek inhibitors (PMID: 12370306, PMID: 19915144, PMID: 26399658).
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_002755.3
gDNA chr15:g.66436798T>C
cDNA c.344T>C
Protein p.L115P
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_017022411.2 chr15:g.66436798T>C c.344T>C p.L115P RefSeq GRCh38/hg38
NM_002755 chr15:g.66436798T>C c.344T>C p.L115P RefSeq GRCh38/hg38
XM_017022411 chr15:g.66436798T>C c.344T>C p.L115P RefSeq GRCh38/hg38
NM_002755.3 chr15:g.66436798T>C c.344T>C p.L115P 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
MAP2K1 L115P melanoma resistant Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) did not inhibit proliferation of melanoma cells expressing Map2k1 L115P (PMID: 19915144). 19915144
MAP2K1 L115P melanoma resistant CI-1040 Preclinical - Cell culture Actionable In a preclinical study, CI-1040 (PD184352) did not inhibit proliferation of melanoma cells expressing Map2k1 L115P (PMID: 19915144). 19915144
MAP2K1 L115P Advanced Solid Tumor resistant CI-1040 Preclinical - Cell culture Actionable In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of Map2k1 L115P expressed in transformed human kidney cells (PMID: 12370306). 12370306
BRAF V600E MAP2K1 L115P melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P 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 expressing MAP2K1 L115P in culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 L115P melanoma resistant PD-0325901 Preclinical Actionable In a preclinical study, over expression of MAPK21 L115P in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 L115P colorectal cancer sensitive SCH772984 Preclinical - Cell culture Actionable In a preclinical study, SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer resistant Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture, likely due to the acquired secondary resistance mutation MAP2K1 L115P (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Alpelisib + Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MAP2K1 mutant Erdheim-Chester disease sensitive Cobimetinib Guideline Actionable Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). detail...
MAP2K1 mutant Erdheim-Chester disease sensitive Trametinib Guideline Actionable Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). detail...
Molecular Profile Protein Effect Treatment Approaches
MAP2K1 L115P gain of function
BRAF V600E MAP2K1 L115P