The third group currently includes residue P511. P511 has the highest relative solvent accessibility (.40%) among the 23 mutation sites and is located on a loop region of the structure. The underlying mechanism for the association of P511H and P511L mutations with HIBM is elusive without further data, but mutation of a proline to any other residue type will inevitably change the flexibility of the loop region around this residue and could thus change the allostery of full length GNE in the higher-order oligomeric state.