The Hox proteins play a role in development and cellular differentiation by regulating downstream target genes. Specifically, the Hox proteins direct DNA-protein and protein-protein interactions that assist in determining the morphologic features associated with the anterior-posterior body axis. HoxD13 is a sequence-specific transcription factor that provides cells with specific positional identities on the anterior-posterior axis of developing mammals. Defects in HoxD13 are the cause of synpolydactyly (SPD). SPD is a limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance. Defects in HoxD13 are also the cause of brachydactyly type D and type E.