SPOP is a substrate adaptor protein within a larger ubiquitin ligase complex. It binds to specific substrate proteins which subsequently are modified by attachment of ubiquitin moieties. Protein ubiquitination is involved in many cellular processes, most notably in protein degradation through the proteasome.
Thus far, four germline mutations with LoF have been described (Thr25Ala, Tyr83Cys, Gly132Val, Arg138Cys) and shown to reduce degradation of the BET proteins (i.e., BRD2, BRD3, BRD4) in a dominant-negative manner. Similar mutations with LoF properties have been previously also described as a oncogenic somatic cancer driver mutations in prostate cancer (Theurillat, 2014; Janouskova, 2017).
SPOP LoF