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, two germline mutations with GoF have been described (Arg121Gln and Asp144Asn) and shown to promote enhanced degradation of the BET proteins (i.e., BRD2, BRD3, BRD4) (Nabais-Sa, 2020).
Arg121Gln has been previously also described as a putative oncogenic somatic cancer driver mutations in endometrial cancer (Janouskova, 2017).
SPOP GoF