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Gene | MAP2K1 |
Variant | L98_K104delinsQ |
Impact List | indel |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 L98_K104delinsQ results in the deletion of seven amino acids in the protein kinase domain of the Map2k1 protein from amino acids 98 to 104, combined with the insertion of a glutamine (Q) at the same site (UniProt.org). L98_K104delinsQ results in increased activation of Map2k1 and elevated phosphorylation of Erk and Akt in culture (PMID: 29768711), and has been demonstrated to confer resistance to Mek inhibitors (PMID: 29768711). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 L98_K104delinsQ |
Transcript | NM_002755.4 |
gDNA | chr15:g.66436747_66436764del18 |
cDNA | c.293_310del18 |
Protein | . |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002755 | chr15:g.66436747_66436764del18 | c.293_310del18 | . | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66436747_66436764del18 | c.293_310del18 | . | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66436747_66436764del18 | c.293_310del18 | . | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 L98_K104delinsQ | lymphatic system cancer | predicted - resistant | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with Langerhans cell histiocytosis harboring MAP2K1 L98_K104delinsQ demonstrated progressive disease when treated with Mekinist (trametinib) (PMID: 29768711). | 29768711 |
MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 |
MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 |
MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, U0126 treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 |
MAP2K1 L98_K104delinsQ | Advanced Solid Tumor | resistant | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, SCH772984 treatment failed to inhibit activation of Mek and Erk in human cells expressing MAP2K1 L98_K104delinsQ in culture (PMID: 29768711). | 29768711 |