Mutations in IPEX: Gene organization and selected mutations in FOXP3 and associated functional domains of the gene product

FOXP3, a member of the forkhead box P (FOXP) family of transcription factors, encodes a 431 amino acid protein fundamental to the differentiation of CD4+ regulatory T cells (Treg). In addition to the forkhead DNA-binding domain that interacts with the interleukin-2 (IL-2) promoter and other target genes, FOXP3 also contains an N-terminal proline-rich domain which regulates transcription. A zinc finger motif may be involved in protein-DNA interactions, while a leucine zipper domain mediates homo and heterodimerization with FOXP3 and other FOXP transcription factors. Except for the zinc finger motif, mutations have been described in patients with IPEX in each of these coding regions.