Molecular characteristics

PSMD12 encodes a subunit of 19S regulatory particle from proteasome 26S. Its disruption alters the assembly of the proteasome and leads to an accumulation of polyubiquitinated proteins in the cell due to proteasomal dysfunction.

 Thus far, all identified genetic variants altering PSMD12 function are de novo. These are either truncating nonsense mutations or CNV deletions of the entire PSMD12 gene and neighboring genes. According to the preliminary functional investigations, the pathomechanism would be haploinsufficiency.