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8.A.193. The Phosphate Transporter Regulator Tmem174 (Tmem174) Family

Renal type II sodium-dependent inorganic phosphate (Pi) transporters NaPi2a and NaPi2c cooperate with other organs to strictly regulate the plasma Pi concentration. A high Pi load induces expression and secretion of the phosphaturic hormones parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) that enhance urinary Pi excretion and prevent the onset of hyperphosphatemia. Sasaki et al. 2022 investigated the role of Tmem174 and observed evidence for gene co-expression networks in NaPi2a and NaPi2c function. Tmem174 is localized in the renal proximal tubules and interacts with NaPi2a, but not NaPi2c. In Tmem174-knockout (KO) mice, the serum FGF23 concentration was markedly increased, but increased Pi excretion and hypophosphatemia were not observed. Tmem174-KO mice exhibit reduced NaPi2a responsiveness to FGF23 and PTH administration. A dietary Pi load causes marked hyperphosphatemia and abnormal NaPi2a regulation in Tmem174-KO mice. Thus, Tmem174 is thought to be associated with FGF23 induction in bones and the regulation of NaPi2a to prevent an increase in the plasma Pi concentration due to a high Pi load and kidney injury (Sasaki et al. 2022).

References associated with 8.A.193 family:

Gaither, M.R., G.A. Gkafas, M. de Jong, F. Sarigol, F. Neat, T. Regnier, D. Moore, D.R. GrÓ§cke, N. Hall, X. Liu, J. Kenny, A. Lucaci, M. Hughes, S. Haldenby, and A.R. Hoelzel. (2018). Genomics of habitat choice and adaptive evolution in a deep-sea fish. Nat Ecol Evol 2: 680-687. 29507380
Sasaki, S., Y. Shiozaki, A. Hanazaki, M. Koike, K. Tanifuji, M. Uga, K. Kawahara, I. Kaneko, Y. Kawamoto, P. Wiriyasermkul, T. Hasegawa, N. Amizuka, K.I. Miyamoto, S. Nagamori, Y. Kanai, and H. Segawa. (2022). Tmem174, a regulator of phosphate transporter prevents hyperphosphatemia. Sci Rep 12: 6353. 35428804