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Functional characterization of a novel ZIP8 variant causing impaired manganese homeostasis and congenital disorders of glycosylation
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DOI：10.1007/s10534-026-00862-2.png)
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Abstract
En 中文
ZIP8, encoded by SLC39A8, mediates cellular uptake of divalent metal ions, including manganese (Mn). Mutations in SLC39A8 cause a congenital disorder of glycosylation (CDG) associated with Mn deficiency (SLC39A8-CDG). Here, we report a novel case of SLC39A8-CDG harboring a previously unreported mutation (p.F206I) in the transmembrane domain 3 (TMD3). The patient showed markedly low serum Mn levels and abnormal glycosylation. To evaluate the functional consequences of this variant, we generated cells expressing hZIP8-F206I. Mn, cadmium, and zinc uptake levels in cells expressing hZIP8-F206I were approximately half of those in cells expressing wild-type hZIP8. The mutant hZIP8 also showed reduced plasma membrane localization. These findings suggest that this previously unreported mutation in TMD3 significantly impairs ZIP8-mediated metal transport, leading to CDG.
Keywords:
SLC39A8
ZIP8
Manganese
Congenital disorder of glycosylation
Metal transporter
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