Abstract
SLC10A7, encoded by the so-called SLC10A7 gene, is the seventh member of a human sodium/bile acid cotransporter family, known as the SLC10 family. Despite similarities with the other members of the SLC10 family, SLC10A7 does not exhibit any transport activity for the typical SLC10 substrates and is then considered yet as an orphan carrier. Recently, SLC10A7 mutations have been identified as responsible for a new Congenital Disorder of Glycosylation (CDG). CDG are a family of rare and inherited metabolic disorders, where glycosylation abnormalities lead to multisystemic defects. SLC10A7-CDG patients presented skeletal dysplasia with multiple large joint dislocations, short stature and amelogenesis imperfecta likely mediated by glycosaminoglycan (GAG) defects. Although it has been demonstrated that the transporter and substrate specificities of SLC10A7, if any, differ from those of the main members of the protein family, SLC10A7 seems to play a role in Ca2+ regulation and is involved in proper glycosaminoglycan biosynthesis, especially heparan-sulfate, and N-glycosylation. This paper will review our current knowledge on the known and predicted structural and functional properties of this fascinating protein, and its link with the glycosylation process.
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Abbreviations
- CDG:
-
Congenital Disorders of Glycosylation
- GAG:
-
Glycosaminoglycans
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Funding
This work was supported by grants from the Agence Nationale de la Recherche through the SKELGAG project and EUROGLYCAN-omics under the frame of E-RARE-3, the ERA-Net for Research on Rare Diseases and within the scope of the International Associated Laboratory “Laboratory for the Research on Congenital Disorders of Glycosylation—from cellular mechanisms to cure—GLYCOLAB4CDG”.
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ZD and JD wrote the manuscript with support from DL, VCD and FF. Figures have been made by AL and DL. All authors discussed and revised the manuscript.
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Durin, Z., Dubail, J., Layotte, A. et al. SLC10A7, an orphan member of the SLC10 family involved in congenital disorders of glycosylation. Hum Genet 141, 1287–1298 (2022). https://doi.org/10.1007/s00439-021-02420-x
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DOI: https://doi.org/10.1007/s00439-021-02420-x