While yW and its derivatives are biosynthesized by five enzymes, known as tRNA-yW Synthesizing Proteins 1-5 (TYW1-5) [49, 50], epigenetic silencing of TYW2 was found to be the leading cause for yW deficiency in cancer [10, 49]. This evidence concerns the gene TYW2 and hyperinsulinemic hypoglycemia, familial, 4.