The transcription factors of the class forkhead (or winged helix) box, also called FOX, is an evolutionary ancient gene family that is named after the Drosophila melanogaster gene fork head (fkh), the first protein in the FOX family that was discovered. This family is characterized by the forkhead box, a sequence of 80 to 100 amino acids forming the DNA-binding domain. This motif is also called the winged helix because of its butterfly-like structure.
Fox proteins have important biological functions, such as cell growth, proliferation, cell cycle control, epithelial cell & erythrocyte differentiation, embryonic development and longevity.
Mutations in members of the FOX gene family lead to diseases with phenotypes ranging from T-cell differentiation to speech impediments. One fascinating example is FOXP2 that is shown to be important for speech acquisition in humas. FOXP2 differs in human by only two amino acids from gorilla and chimpanzee and these residues are thougth to create a protein kinase C phosphorylation site that might have been crucial for the adaption needed for speech development. Another example is FOXP3, currently used as a marker for CD25+ CD4+ regulatory T-cells. Mutations in FOXP3 have been linked to neonatal diabetes, ployendocrinopathy and enteropathy (IPEX) in humans.