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Gene | MAP2K1 |
Variant | V60E |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 V60E does not lie within any known functional domains of the Map2k1 protein (UniProt.org). V60E confers a gain of function to Map2k1 as demonstrated by increased Erk signaling (PMID: 28263969), transformation activity in cultured cells and increased proliferation in a competition assay (PMID: 36442478), and tumor formation in orthotopic mouse models (PMID: 28263969), and demonstrates resistance to some Braf inhibitors (PMID: 24265153, PMID: 28263969, PMID: 36442478). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 V60E |
Transcript | NM_002755.4 |
gDNA | chr15:g.66435125T>A |
cDNA | c.179T>A |
Protein | p.V60E |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017022412 | chr15:g.66435191T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66435125T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
XM_011521783 | chr15:g.66435191T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66435125T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
XM_017022411 | chr15:g.66435125T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
XM_011521783.4 | chr15:g.66435191T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66435125T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66435125T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
NM_001411065.1 | chr15:g.66435191T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
XM_011521783.3 | chr15:g.66435191T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
XM_017022412.1 | chr15:g.66435191T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66435125T>A | c.179T>A | p.V60E | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E MAP2K1 V60E | melanoma | sensitive | VX-11e | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated sensitivity to treatment with VX-11e, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 |
BRAF V600E MAP2K1 V60E | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V60E was resistant to Tafinlar (dabrafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 V60E | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). | 24265153 |
BRAF V600E MAP2K1 V60E | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V60E was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 V60E | melanoma | resistant | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V60E was resistant to Braftovi (encorafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 V60E | 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 V60E in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 V60E | 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 V60E in culture (PMID: 36442478). | 36442478 |
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R | melanoma | predicted - resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistance-associated mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 |