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Gene | MAP2K1 |
Variant | F129L |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 F129L lies within the protein kinase domain of the Map2k1 protein (UniProt.org). F129L confers a gain of function to the Map2k1 protein as demonstrated by increased kinase activity compared to wild-type, activation of downstream Erk signaling, and increased binding affinity to c-Raf (PMID: 21705440) and also demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 F129L |
Transcript | NM_002755.4 |
gDNA | chr15:g.66436839T>C |
cDNA | c.385T>C |
Protein | p.F129L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002755 | chr15:g.66436839T>C | c.385T>C | p.F129L | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66436839T>C | c.385T>C | p.F129L | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66436839T>C | c.385T>C | p.F129L | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66436839T>C | c.385T>C | p.F129L | RefSeq | GRCh38/hg38 |
XM_017022411 | chr15:g.66436839T>C | c.385T>C | p.F129L | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66436839T>C | c.385T>C | p.F129L | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 F129L | ovarian serous carcinoma | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, MAP2K1 F129L was identified in a low grade serous ovarian cancer cell line that developed resistance to treatment with Mekinist (trametinib) in culture (PMID: 36198031). | 36198031 |
MAP2K1 F129L | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 F129L in culture (PMID: 36442478). | 36442478 |
MAP2K1 F129L | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 F129L | ovarian serous carcinoma | resistant | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a low grade serous ovarian cancer cell line harboring MAP2K1 F129L was resistant to treatment with Mektovi (binimetinib) in culture (PMID: 36198031). | 36198031 |
MAP2K1 F129L | ovarian serous carcinoma | resistant | Refametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a low grade serous ovarian cancer cell line harboring MAP2K1 F129L was resistant to treatment with Refametinib (BAY86-9766) in culture (PMID: 36198031). | 36198031 |
MAP2K1 F129L | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 F129L | ovarian serous carcinoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a low grade serous ovarian cancer cell line harboring MAP2K1 F129L was resistant to treatment with Koselugo (selumetinib) in culture (PMID: 36198031). | 36198031 |
MAP2K1 F129L | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 F129L | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 F129L | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 F129L | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 F129L displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 F129L | colorectal cancer | sensitive | RO4927350 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a colorectal cancer cell line harboring MAP2K1 F129L demonstrated sensitivity to treatment with RO4927350 in culture and in cell line xenograft models, demonstrating inhibition of tumor growth (PMID: 21705440). | 21705440 |