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Gene | MAP2K1 |
Variant | K57T |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 K57T lies within the negative regulatory region of the Map2k1 protein (PMID: 24241536). K57T confers a gain of function to Map2k1 as demonstrated by increased Erk1/2 phosphorylation (PMID: 30341394, PMID: 32641410) and transformation activity in cultured cells and increased proliferation in a competition assay (PMID: 36442478), and occurs as a secondary drug resistance mutation in the context of BRAF inhibitors (PMID: 26644315, PMID: 28819429, PMID: 30341394). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 K57T |
Transcript | NM_002755.4 |
gDNA | chr15:g.66435116A>C |
cDNA | c.170A>C |
Protein | p.K57T |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017022411.2 | chr15:g.66435116A>C | c.170A>C | p.K57T | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66435116A>C | c.170A>C | p.K57T | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66435116A>C | c.170A>C | p.K57T | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66435116A>C | c.170A>C | p.K57T | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66435116A>C | c.170A>C | p.K57T | RefSeq | GRCh38/hg38 |
XM_017022411 | chr15:g.66435116A>C | c.170A>C | p.K57T | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 K57T | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited viability of a transformed cell line expressing MAP2K1 K57T in culture (PMID: 36442478). | 36442478 |
MAP2K1 K57T | colorectal cancer | predicted - resistant | Cetuximab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with colorectal cancer developed liver metastases harboring MAP2K1 K57T that were insensitive to Erbitux (cetuximab) treatment and the mutation was confirmed to cause resistance in human colorectal cancer cell lines in culture (PMID: 26644315). | 26644315 |
MAP2K1 K57T | colorectal cancer | resistant | Panitumumab | Preclinical | Actionable | In a preclinical study, a colorectal cancer cell line expressing MAP2K1 K57T was resistant to Vectibix (panitumumab) in culture (PMID: 26644315). | 26644315 |
MAP2K1 K57T | colorectal cancer | sensitive | Panitumumab + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a combination of Vectibix (panitumumab) and Mekinist (trametinib) caused tumor regression in a patient’s colorectal cancer metastases harboring MAP2K1 K57T after being identified pre-clinically as a combination likely to inhibit MAP2K1 K57T expressing colorectal cancer (PMID: 26644315). | 26644315 |
MAP2K1 K57T | colorectal cancer | sensitive | Cetuximab + Trametinib | Preclinical | Actionable | In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57T in culture (PMID: 26644315). | 26644315 |