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Gene | MAP2K1 |
Variant | Q56P |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 Q56P does not lie within any known functional domains of the Map2k1 protein (UniProt.org). Q56P confers a gain of function to the Map2k1 protein as indicated by increased kinase activity and the ability to transform cultured cells (PMID: 7651428, PMID: 22327936, PMID: 25351745) and increased proliferation in a competition assay (PMID: 36442478), and demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 Q56P |
Transcript | NM_002755.4 |
gDNA | chr15:g.66435113A>C |
cDNA | c.167A>C |
Protein | p.Q56P |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002755.4 | chr15:g.66435113A>C | c.167A>C | p.Q56P | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66435113A>C | c.167A>C | p.Q56P | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66435113A>C | c.167A>C | p.Q56P | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66435113A>C | c.167A>C | p.Q56P | RefSeq | GRCh38/hg38 |
XM_017022411 | chr15:g.66435113A>C | c.167A>C | p.Q56P | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66435113A>C | c.167A>C | p.Q56P | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 Q56P | lung adenocarcinoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). | 26582713 |
MAP2K1 Q56P | stomach cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a gastric cancer cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). | 26582713 |
MAP2K1 Q56P | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 Q56P in culture (PMID: 32641410). | 32641410 |
MAP2K1 Q56P | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 Q56P in culture (PMID: 36442478). | 36442478 |
MAP2K1 Q56P | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 Q56P | lung adenocarcinoma | sensitive | PD-0325901 | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to PD-0325901, resulting in decreased cell viability (PMID: 26582713). | 26582713 |
MAP2K1 Q56P | lung adenocarcinoma | sensitive | Refametinib | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Refametinib (BAY86-9766), resulting in decreased cell viability (PMID: 26582713). | 26582713 |
MAP2K1 Q56P | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 Q56P | lung adenocarcinoma | sensitive | Selumetinib | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Selumetinib (AZD6244), resulting in decreased cell viability (PMID: 26582713). | 26582713 |
MAP2K1 Q56P | stomach cancer | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited growth of a gastric cancer cell line that requires MAP2K1 Q56P and inhibited phosphorylation of ERK in these cells (PMID: 22327936). | 22327936 |
MAP2K1 Q56P | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited colony formation of transformed cells expressing MAP2K1 Q56P in culture (PMID: 25351745). | 25351745 |
MAP2K1 Q56P | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 Q56P | Erdheim-Chester disease | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 Q56P mutation had a reduction of lymphatic infiltrates to background within a month of receiving Cotellic (cobimetinib) therapy (PMID: 26566875). | 26566875 |
MAP2K1 Q56P | Erdheim-Chester disease | 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 stable disease in 6% (1/18) of patients, including a complete response in a patient with Erdheim-Chester disease harboring MAP2K1 Q56P (PMID: 30867592; NCT01953926). | 30867592 |
MAP2K1 Q56P | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 Q56P | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 Q56P | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 Q56P displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 Q56P | lung cancer | predicted - sensitive | LY3214996 | Preclinical - Cell culture | Actionable | In a preclinical study, a lung cancer cell line harboring MAP2K1 Q56P was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895). | 31744895 |