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Gene | MAP2K1 |
Variant | K57N |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 K57N lies within the negative regulatory region of the Map2k1 protein (PMID: 24241536). K57N confers a gain of function to Map2k1 as demonstrated by increased autophosphorylation (PMID: 29753091) and Erk phosphorylation (PMID: 18632602, PMID: 29753091), increased cell proliferation and cell viability in two different cell lines (PMID: 29533785, PMID: 18632602), transformation of cultured cells (PMID: 25351745, PMID: 36442478), 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 K57N |
Transcript | NM_002755.4 |
gDNA | chr15:g.66435117G>C |
cDNA | c.171G>C |
Protein | p.K57N |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002755 | chr15:g.66435117G>C | c.171G>C | p.K57N | RefSeq | GRCh38/hg38 |
XM_017022411 | chr15:g.66435117G>C | c.171G>C | p.K57N | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66435117G>C | c.171G>C | p.K57N | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66435117G>C | c.171G>C | p.K57N | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66435117G>C | c.171G>C | p.K57N | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66435117G>C | c.171G>C | p.K57N | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 K57N | lung adenocarcinoma | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited phosphorylation of ERK in cells expressing MAP2K1 K57N and inhibited MAP2K1 K57N-dependent growth in cell culture (PMID: 18632602). | 18632602 |
MAP2K1 K57N | colorectal cancer | resistant | Cetuximab | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines expressing MAP2K1 K57N were insensitive to Erbitux (cetuximab) in culture (PMID: 26644315). | 26644315 |
MAP2K1 K57N | colorectal cancer | resistant | Panitumumab | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines expressing MAP2K1 K57N were insensitive to Vectibix (panitumumab) in culture (PMID: 26644315). | 26644315 |
MAP2K1 K57N | colorectal cancer | resistant | Panitumumab | Case Reports/Case Series | Actionable | In a retrospective analysis, two patients with metastatic RAS/BRAF wild-type colorectal cancer demonstrated progressive disease following treatment with Vectibix (panitumumab) and via analysis of archived pretreatment tumor biopsy samples and post-progression liquid biopsy both were found to harbor MAP2K1 K57N (PMID: 36419886). | 36419886 |
MAP2K1 K57N | colorectal cancer | sensitive | Cetuximab + Trametinib | Preclinical | Actionable | In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57N in culture (PMID: 26644315). | 26644315 |
MAP2K1 K57N | colorectal cancer | sensitive | Panitumumab + Trametinib | Preclinical | Actionable | In a preclinical study, Vectibix (panitumumab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57N in culture (PMID: 26644315). | 26644315 |
MAP2K1 K57N | lymphatic system cancer | sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 K57N mutation had a sustained clinical response to Mekinist (trametinib) for over 6 months (PMID: 26566875). | 26566875 |
MAP2K1 K57N | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited colony formation of transformed cells expressing MAP2K1 K57N in culture (PMID: 25351745). | 25351745 |
MAP2K1 K57N | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 K57N | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 K57N | Advanced Solid Tumor | resistant | PD98059 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 K57N | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 K57N | Advanced Solid Tumor | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 K57N | Advanced Solid Tumor | resistant | AZD8330 | Preclinical - Cell culture | Actionable | In a preclinical study, Map2k1 K57N displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). | 29753091 |
MAP2K1 K57N | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in transformed cells expressing MAP2K1 K57N in culture (PMID: 32641410). | 32641410 |
MAP2K1 K57N | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 K57N in culture (PMID: 36442478). | 36442478 |
MAP2K1 K57N | lung non-squamous non-small cell carcinoma | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in a radiographic response with a decrease in the size of multiple metastatic sites in a patient with non-squamous non-small cell lung cancer harboring MAP2K1 K57N (PMID: 36455195). | 36455195 |
MAP2K1 K57N | Advanced Solid Tumor | predicted - sensitive | SCH772984 | Preclinical - Biochemical | Actionable | In a preclinical study, SCH772984 inhibited downstream signaling in transformed cells expressing MAP2K1 K57N in culture (PMID: 32641410). | 32641410 |