Mutations in MAP2K1, which encodes the dual-specificity kinase MEK1 protein in the MAPK pathway, have been identified in 27.5% of cases with LCH, thus explaining MAPK pathway activation in the absence of the BRAF mutation. MAP2K1 and BRAF mutations were found to be mutually exclusive, as would be expected since MEK1 is directly downstream BRAF within the MAPK pathway [38]. This evidence concerns the gene MAP2K1 and Langerhans cell histiocytosis.