In line with this, germ line SHORT syndrome-related mutations in PIK3R1, which preferably target the cSH2 p85α domain, displayed in our yeast system an ability to modulate p110α indistinguishable from that of the wild-type p85α protein, even when large C-terminal truncations eliminating most of the cSH2 were assayed. Here, PIK3R1 is linked to SHORT syndrome.