WASp genomic organization and protein structure. (A) Schematic diagram of WASp genomic structure. The 12 exons are colored and numbered. Unshaded blocks represent uncoded regions. Numbers above the blocks indicate base pairs. (B) Line diagram representing the WASp protein. Colored regions correspond to encoding exons, and numbers indicate amino acids. (C) Schematic diagram representing the WASp protein. The EVH1, ⁵⁴  basic (B), minimal high-affinity Cdc42-binding site (CRIB), ^12,13  poly-proline (PPPP), and VCA⁶¹  domains/regions are shown. Amino acids are numbered below the protein. The black line above the CRIB domain indicates the VCA binding region (amino acids 242-310).¹¹  Red numbered circles denote mutational hotspots⁶²  as follows: 1 indicates T45M; 2, R86S/G/C/H/L; 3, IVS6 (+5g>a); 4, R211X; and 5, IVS8 (+1g>a/c/t). Mutations resulting in constitutive activation are indicated by asterisks: red indicates L270P¹⁰ ; blue, L272P (P. Ancliff and A.J.T., unpublished, September 25, 2003); and green, I294T (Ancliff P.J., Blundell M.P., G.O.C., Calle Y., Kempski H., Toscano M., Jones G.E., Ridley A.J., Sinclair J., Kinnon C., Hann I.M., Gale R.E., de Botton S., W.V., Linch D.C., A.J.T., Unregulated activation of the actin cytoskeleton promotes haematopoietic cell death and causes X-linked neutropenia, manuscript submitted, September 1, 2004).