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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 | chr15:g.66435116A>C | c.170A>C | p.K57T | RefSeq | GRCh38/hg38 |
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 |
XM_017022411.3 | 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 |
NM_002755.3 | 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 |
---|---|---|---|---|---|---|---|
BRAF V600E MAP2K1 K57T | refractory hairy cell leukemia | predicted - sensitive | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with hairy cell leukemia harboring BRAF V600E who relapsed after initial response to Zelboraf (vemurafenib) and was found to have acquired multiple clones with Mek/Erk activating mutations, including MAP2K1 K57T, demonstrated a sustained response greater than 12 months to combined Zelboraf (vemurafenib) and Cotellic (cobimetinib) treatment (PMID: 30341394). | 30341394 |
BRAF V600E MAP2K1 K57T | hairy cell leukemia | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a single patient with hairy cell leukemia harboring BRAF V600E, who relapsed after a 38 week remission in response to Zelboraf (vemurafenib) treatment, was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant (PMID: 30341394). | 30341394 |
BRAF V600E MAP2K1 K57T | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | melanoma | resistant | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Mektovi (binimetinib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Tafinlar (dabrafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | melanoma | resistant | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Braftovi (encorafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | 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 K57T in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | melanoma | sensitive | Binimetinib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Braftovi (encorafenib) and Mektovi (binimetinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 K57T | colorectal cancer | predicted - resistant | Cetuximab + Fluorouracil + Leucovorin + Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (MODUL), a patient with metastatic colorectal cancer harboring BRAF V600E was found to have acquired MAP2K1 K57T prior to progression on treatment with the combination of Zelboraf (vemurafenib), Erbitux (cetuximab), Adrucil (fluorouracil), and Wellcovorin (leucovorin) (PMID: 36921494; NCT02291289). | 36921494 |