Protein domains and disease-causing mutations in the myotubularin, amphiphysin, and dynamin families.

Myotubularin contains a PH-GRAM domain that may bind lipids and a coil-coiled-PDZ binding site to form homo- and hetero-dimers with other members of the myotubularin family. Only the disease-causing missense mutations in MTM1 are represented, based on the international UMD-MTM1 database, existing currently in a local version in Strasbourg (France). MTM1 mutations identified in more than two patients are R69C(9 families), P205L(5), V227M(3), R241C(13), G378R(4), E404K(4), and Y397C(5). AMPH1 and BIN1 possess an N-BAR domain able to sense and eventually curve membrane and a C-terminal SH3 domain binding to proteins with proline-rich domains, such as dynamins [48], [88]. In addition some isoforms have clathrin-binding and Myc-binding domains (CBD, MBD); a phosphoinositide-binding motif is present between the BAR and MBD domains specifically in skeletal muscle. DNM2 contains a GTPase domain, a central middle (MID) domain, a Pleckstrin Homology (PH) domain, a GTPase Effector Domain (GED), and a C-terminal Proline Rich Domain (PRD). Dominant mutations in DNM2 lead to either centronuclear myopathy (above), or peripheral CMT neuropathy (below). Only coding mutations are listed for all genes.