Spondylocheirodysplastic Ehlers-Danlos syndrome (SCD-EDS) and the mutant zinc transporter ZIP13

Rare Dis. 2014 Dec 1;2(1):e974982. doi: 10.4161/21675511.2014.974982. eCollection 2014.

Abstract

The zinc transporter protein ZIP13 plays crucial roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). We recently reported that the pathogenic mutations in ZIP13 reduce its functional protein level by accelerating the protein degradation via the VCP-linked ubiquitin proteasome pathway, resulting in the disturbance of intracellular zinc homeostasis that appears to contribute to SCD-EDS pathogenesis. Finally, we implicate that possible therapeutic approaches for SCD-EDS would be based on regulating the degradation of the pathogenic mutant ZIP13 proteins.

Keywords: SCD-EDS; SLC39A13; ZIP13; corrector; degradation; pathogenic mutation; potentiator; zinc transporter.