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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_017022411.3 | 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 | 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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK rearrange MAP2K1 K57N | lung non-small cell carcinoma | sensitive | Ceritinib + Selumetinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of Koselugo (selumetinib), resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791). | 25394791 |
BRAF V600E MAP2K1 K57N | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57N was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57N | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57N was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57N | melanoma | sensitive | Cobimetinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57N in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57N | lung adenocarcinoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, MAP2K1 K57N was identified on the post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring BRAF V600E, who previously responded to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 32388065). | 32388065 |