In contrast to SHORT syndrome, mutations in the inter SH2 domain of PIK3R1, mostly leading to skipping of exon 11, were shown in 2014 to activate PI3K in vitro and to cause immunodeficiency (APDS2) (Deau et al., 2014; Lucas et al., 2014b) similar to that caused by activating mutations in p110δ (APDS1) (Angulo et al., 2013; Lucas et al., 2014a). Here, PIK3R1 is linked to immunodeficiency disease.