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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).

References associated with 9.B.419 family:

Bausch, B., F. Schiavi, Y. Ni, J. Welander, A. Patocs, J. Ngeow, U. Wellner, A. Malinoc, E. Taschin, G. Barbon, V. Lanza, P. Söderkvist, A. Stenman, C. Larsson, F. Svahn, J.L. Chen, J. Marquard, M. Fraenkel, M.A. Walter, M. Peczkowska, A. Prejbisz, B. Jarzab, K. Hasse-Lazar, S. Petersenn, L.C. Moeller, A. Meyer, N. Reisch, A. Trupka, C. Brase, M. Galiano, S.F. Preuss, P. Kwok, N. Lendvai, G. Berisha, &.#.2.1.4.;. Makay, C.C. Boedeker, G. Weryha, K. Racz, A. Januszewicz, M.K. Walz, O. Gimm, G. Opocher, C. Eng, H.P.H. Neumann, and. (2017). Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention. JAMA Oncol 3: 1204-1212. 28384794
Flores, S.K., Y. Deng, Z. Cheng, X. Zhang, S. Tao, A. Saliba, I. Chu, N. Burnichon, A.P. Gimenez-Roqueplo, E. Wang, R.C.T. Aguiar, and P.L.M. Dahia. (2020). Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking. J Clin Endocrinol Metab 105:. 32575117