STXBP2 and macrophage activation syndrome: Of these 26 genes believed to be causal of an IEI and PML, 24 (92%) are also linked with hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)—a severe hyper-inflammation syndrome associated with several IEI genes, most notably in 4 genes (PRF1, STX11, STXBP2, UNC13D) causing familial forms of the syndrome.