2.A.106.2.2
Ca²⁺:H⁺ antiporter, TMEM165 (PT27; TPARL; SLC64A1) of 324 aas and 7 TMSs in a 1 (N-terminal) + 3 + 3 TMS arrangement (Demaegd et al. 2013).  It may be both a Ca²⁺:H⁺ and a Mn²⁺:H⁺ antiporter (Dulary et al. 2016), catalyzing uptake of Mn²⁺ from the cytoplasm into the golgi lumen.  TMEM165 has been linked to congenital disorders of glycosylation (CDG) (Foulquier et al. 2012). It may influence glycosylation due to its Mn²⁺ transport activity that regulates Mn²⁺ homeostasis in the golgi (Thines et al. 2018). TMEM165 is also required for milk production (Snyder et al. 2019). Human Both Ca²⁺ and Mn²⁺ are required for proper protein glycosylation in cells (Stribny et al. 2020). TMEM165, a Golgi transmembrane protein, is a novel marker for hepatocellular carcinoma, and its depletion impairs invasion activity (Lee et al. 2018). The pathogenicity of TMEM165 variants using structural modeling based on AlphaFold 2 predictions has been presented (Legrand et al. 2023).