The GoF MAX variants, the cause of polydactyly-macrocephaly syndrome, are present in the b-HLH-LZ domain, where the mutant MAX binds its target E-box sequence with a lower apparent affinity, leading to a more efficient heterodimerization with Myc and an increase in transcriptional activity of Myc (29). The gene discussed is MAX; the disease is polydactyly-macrocephaly syndrome.