9.B.147. The Transmembrane 127 (TMEM127) Family
TMEM127 is encoded by a tumor suppressor gene associated with pheochromocytomas, paragangliomas, and renal carcinomas (Bausch et al. 2017; Flores et al. 2020). To better understand the structure of TMEM127, Flores et al. 2020 undertook cellular and molecular evaluation of patient-derived germline variants. They identified 3 subgroups of mutations and determined that 71% of the variants studied are likely pathogenic through loss of their membrane-binding ability, stability, and/or internalization capability. TMEM127 is a 4-TMS protein. A C-terminal variant with predominant plasma membrane localization revealed an atypical, extended acidic, dileucine-based motif required for TMEM127 internalization through clathrin-mediated endocytosis. Thus, several germline TMEM127 variants revealed potential structure-function features of TMEM127 (Flores et al. 2020).