SYP and neurodegenerative disease: Furthermore, both variants (rs5847212 and rs139451855) are ~190 to 250 kb upstream of the gene UBE2E2. UBE2E2 interacts with Siah proteins, which regulate synaptophysin degradation; synaptophysin has been associated with long-term potentiation, neurotransmitter release, and neurodegenerative diseases including Alzheimer disease22.