Ubiquitin

Ubiquitin pathway (UBE3A, PARK2, RFWD2 and FBXO40)

The genes UBE3A, PARK2, RFWD2 and FBXO40 are a part of the Ubiquitin pathway and have been implicated as genes that may possibly confer susceptibility to ASD through genome wide CNV association studies. Ubiquitination is a post-translational modification that can alter protein function and target proteins for proteosome degradation. This system can regulate synaptic attributes, including neurotransmitter release, synaptic vesicle recycling in pre-synaptic terminals, dynamic changes in dendritic spines, and post-synaptic density. All four of the genes are ubiquitin-protein ligases. UBE3A is the most studied of the four in relation to autism and PARK2 mutations have been linked to autosomal reccessive juvenile Parkinson's disease.

Ubiquitin may be responsible for the turnover of synaptic components such as neuronal cell-adhesion molecules in a process that involves regulation of activity-dependent synaptic plasticity.