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Gene | MAP2K1 |
Variant | E102_I103del |
Impact List | deletion |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 E102_I103del results in the deletion of two amino acids in the protein kinase domain of the Map2k1 protein from amino acids 102 to 103 (UniProt.org). E102_I103del confers a gain of function to the Map2k1 protein as demonstrated by activity independent of Raf and increased phosphorylation of Mek and Erk relative to wild-type Map2k1 (PMID: 29483135), increased Erk phosphorylation (PMID: 32036070, PMID: 25202140) and Mek homodimerization in culture (PMID: 30377225), increased proliferation in a competition assay, and increased transformation activity in culture (PMID: 36442478). |
Associated Drug Resistance | |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 E102_I103del |
Transcript | NM_002755.4 |
gDNA | chr15:g.66436758_66436763delGAGATC |
cDNA | c.304_309delGAGATC |
Protein | p.E102_I103delEI |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011521783 | chr15:g.66436824_66436829delCCGTAC | c.304_309delCCGTAC | p.P102_Y103delPY | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66436758_66436763delGAGATC | c.304_309delGAGATC | p.E102_I103delEI | RefSeq | GRCh38/hg38 |
XM_017022413 | chr15:g.66485128_66485133delCAGGTG | c.304_309delCAGGTG | p.Q102_V103delQV | RefSeq | GRCh38/hg38 |
XM_017022413.1 | chr15:g.66485128_66485133delCAGGTG | c.304_309delCAGGTG | p.Q102_V103delQV | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66436758_66436763delGAGATC | c.304_309delGAGATC | p.E102_I103delEI | RefSeq | GRCh38/hg38 |
XM_017022412.1 | chr15:g.66436824_66436829delCCGTAC | c.304_309delCCGTAC | p.P102_Y103delPY | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66436758_66436763delGAGATC | c.304_309delGAGATC | p.E102_I103delEI | RefSeq | GRCh38/hg38 |
XM_011521783.3 | chr15:g.66436824_66436829delCCGTAC | c.304_309delCCGTAC | p.P102_Y103delPY | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66436758_66436763delGAGATC | c.304_309delGAGATC | p.E102_I103delEI | RefSeq | GRCh38/hg38 |
XM_011521783.4 | chr15:g.66436824_66436829delCCGTAC | c.304_309delCCGTAC | p.P102_Y103delPY | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66436758_66436763delGAGATC | c.304_309delGAGATC | p.E102_I103delEI | RefSeq | GRCh38/hg38 |
XM_017022411 | chr15:g.66436758_66436763delGAGATC | c.304_309delGAGATC | p.E102_I103delEI | RefSeq | GRCh38/hg38 |
NM_001411065.1 | chr15:g.66436824_66436829delCCGTAC | c.304_309delCCGTAC | p.P102_Y103delPY | RefSeq | GRCh38/hg38 |
XM_017022412 | chr15:g.66436824_66436829delCCGTAC | c.304_309delCCGTAC | p.P102_Y103delPY | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 E102_I103del | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed cells expressing MAP2K1 E102_I103del were less sensitive to Mekinist (trametinib) compared to to similar mutations in the negative regulatory domain of the Map2k1 protein in culture (PMID: 32641410). | 32641410 |
MAP2K1 E102_I103del | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing MAP2K1 E102_I103del were resistant to Mekinist (trametinib) in culture (PMID: 36442478). | 36442478 |
MAP2K1 E102_I103del | histiocytosis | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a clinical case study, Cotellic (cobimetinib) resulted in dramatic clinical improvement and decreased variant allele frequency in a patient with mixed histiocytosis harboring MAP2K1 E102_I103del, with the patient remaining disease free at least 3 years after treatment initiation (PMID: 36406830). | 36406830 |
MAP2K1 E102_I103del | Advanced Solid Tumor | predicted - sensitive | SCH772984 | Preclinical - Biochemical | Actionable | In a preclinical study, SCH772984 inhibited downstream signaling in transformed cells expressing MAP2K1 E102_I103del in culture (PMID: 32641410). | 32641410 |
MAP2K1 E102_I103del | histiocytosis | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in complete remission of cutaneous lesions and resolution of the pituitary gland enlargement and associated symptoms in a patient with Langerhans cell histiocytosis harboring MAP2K1 E102_I103del (PMID: 35172489). | 35172489 |
MAP2K1 E102_I103del | histiocytosis | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in symptom improvement, resolution of the partial pneumothorax, and reduction in cystic lesions in a patient with pulmonary Langerhans cell histiocytosis harboring MAP2K1 E102_I103del (PMID: 29694792). | 29694792 |
MAP2K1 E102_I103del | histiocytosis | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with Mekinist (trametinib) resulted in complete remission in a pediatric patient with Langerhans cell histiocytosis harboring MAP2K1 E102_I103del, with treatment ongoing for at least 10 months (PMID: 36730444). | 36730444 |