Signal transduction by the FAS receptor whose gene is mutated in ALPS as detailed in the Introduction. (A) Schematic of the signaling complex formed after the engagement of FAS by FAS ligand that leads to apoptosis. Shown at the top left is an example of a mutant FAS receptor chain lacking the death domain bound to a wild-type chain through the PLAD, which prevents it from signaling causing dominant interference. (B) Diagram showing the intron-exon structure of the FAS gene with delineation of exons coding for the extracellular, transmembrane, and intracellular portions of the protein incorporating the death domain and the location and types of mutations associated with ALPS-FAS. It is notable that R250 in the α2 helical region of the death domain is the most frequently altered residue and exhibits haploinsufficiency due to reduced Fas surface expression, as well as dominant interference.^22,23