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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: 22327936, PMID: 7651428) and also demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091). |
Associated Drug Resistance | Y |
Transcript | NM_002755.3 |
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 | 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_017022411.2 | 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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | lymphatic system cancer | 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 | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Mekinist (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 | 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 | 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 |
BRAF V600E MAP2K1 Q56P | melanoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the MEK inhibitor, Koselugo (selumetinib), in cell culture (PMID: 19915144). | 19915144 |
BRAF V600E MAP2K1 Q56P | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 |
BRAF V600E MAP2K1 Q56P | melanoma | sensitive | Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 28655712). | 28655712 |
BRAF V600E MAP2K1 Q56P | melanoma | resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the B-RAF inhibitor PLX4720 in culture (PMID: 19915144). | 19915144 |
BRAF V600E MAP2K1 Q56P | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling in culture (PMID: 22389471). | 22389471 |
BRAF V600E MAP2K1 Q56P | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 |
BRAF V600E MAP2K1 Q56P | melanoma | sensitive | PLX4720 + Selumetinib | Preclinical | Actionable | In a preclinical study, combined treatment with selumetinib and PLX4720 strongly suppressed the emergence of resistant MAP2K1 mutations in BRAF V600E cells in culture (PMID: 19915144). | 19915144 |
BRAF V600E MAP2K1 Q56P | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, the combination of Talfinlar (dabrafenib) and Mekinist (trametinib) resulted in improved growth inhibition in melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 22389471). | 22389471 |
BRAF V600E MAP2K1 Q56P NRAS Q61R | melanoma | sensitive | AZD0364 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD0364 (ATG-017) decreased phosphorylation of Erk target genes and increased expression of apoptosis markers in melanoma cells harboring BRAF V600E, MAP2K1 Q56P, and NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 33273059). | 33273059 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
MAP2K1 Q56P | gain of function | MEK inhibitor (Pan) MEK1 Inhibitor |
BRAF V600E MAP2K1 Q56P | ||
BRAF V600E MAP2K1 Q56P NRAS Q61R |