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Gene | MAP2K1 |
Variant | F53L |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 F53L lies within the negative regulatory region of the Map2k1 protein (PMID: 24241536). F53L results in activation of Map2k1 as indicated by increased Erk and Mek phosphorylation (PMID: 25164765, PMID: 29483135), increased Rsk phosphorylation (PMID: 25351745), transformation activity in culture (PMID: 25351745, PMID: 36442478), and increased proliferation in a competition assay (PMID: 36442478), and demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091, PMID: 36442478). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 F53L |
Transcript | NM_002755.4 |
gDNA | chr15:g.66435103T>C |
cDNA | c.157T>C |
Protein | p.F53L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017022411.3 | chr15:g.66435103T>C | c.157T>C | p.F53L | RefSeq | GRCh38/hg38 |
XM_017022411 | chr15:g.66435103T>C | c.157T>C | p.F53L | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66435103T>C | c.157T>C | p.F53L | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66435103T>C | c.157T>C | p.F53L | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66435103T>C | c.157T>C | p.F53L | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66435103T>C | c.157T>C | p.F53L | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E MAP2K1 F53L | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 F53L | melanoma | conflicting | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 F53L | melanoma | conflicting | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek but not Erk phosphorylation and did not inhibit proliferation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36622773). | 36622773 |
BRAF V600E MAP2K1 F53L | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L was resistant to Tafinlar (dabrafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 F53L | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited Erk and Mek phosphorylation but did not inhibit proliferation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36622773). | 36622773 |
BRAF V600E MAP2K1 F53L | melanoma | sensitive | DS03090629 | Preclinical - Cell culture | Actionable | In a preclinical study, DS03090629 inhibited Erk and Mek phosphorylation and proliferation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36622773). | 36622773 |
BRAF V600E MAP2K1 F53L | melanoma | resistant | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L was resistant to Braftovi (encorafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 F53L | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 F53L | melanoma | sensitive | Binimetinib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Braftovi (encorafenib) and Mektovi (binimetinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 F53L | melanoma | sensitive | Cobimetinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) synergistically inhibited viability in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53L in culture (PMID: 36442478). | 36442478 |