The FOX family of transcription factors is a large group of proteins that share a common DNA binding domain termed a winged-helix or forkhead domain. During early development, FOXP1 and FOXP2 are expressed abundantly in the lung, with lower levels of expression in neural, intestinal and cardiovascular tissues, where they act as transcription repressors. FOXP1 is widely expressed in adult tissues, while neoplastic cells often exhibit a dramatic change in expression level or localization of FOXP1. The gene encoding human FOXP1 maps to chromosome 3p14.1, and the gene encoding human FOXP2 maps to chromosome 7q31. The gene encoding FOXP3, a third member of this family, maps to chromosome Xp11.23. Mutations in this gene cause IPEX, a fatal, X-linked inherited disorder characterized by immune dysregulation. The FOXP3 protein, also known as scurfin, is essential for normal immune homeostasis. Specifically, FOXP3 represses transcription through a DNA binding forkhead domain, thereby regulating T cell activation.
