Schematic representation of GALNT3 structure.

<p>GALNT3 contains 3 domains which comprise a transmembrane domain (TMD) which is formed by residues 20 to 37; a glycosyltransferase domain which is formed by residues 188 to 374; and a carbohydrate-binding domain which is formed by residues 506 to 630, and contains two QXW repeats formed by residues 587–589 and 625–627, respectively. Human GALNT3 has four potential <i>N</i>-linked glycosylation sites (shown as branches) at amino acid residues 132, 297, 484 and 619, respectively <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043205#pone.0043205-Bennett1" target="_blank">[61]</a>; whereas mouse Galnt3 has two potential <i>N</i>-linked glycosylation sites (not shown) at amino acid residues 297 and 484 (NetNGlyc 1.0). Twenty five <i>GALNT3</i> mutations (10 missense, 6 nonsense and 9 frameshift/deletion) have been reported in patients with familial tumoural calcinosis (FTC) and hyperostosis-hyperphosphataemia syndrome (HHS) (asterisked); and details of these 25 <i>GALNT3</i> mutations are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043205#pone-0043205-t001" target="_blank">Table 1</a>. Four <i>GALNT3</i> mutations (Glu281Gly, Leu366Arg, Arg438Cys and 464–508 deletion) have been reported in patients with FTC and HHS (bold and asterisked), thereby indicating that these 2 disorders are allelic variants <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043205#pone.0043205-Joseph1" target="_blank">[3]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043205#pone.0043205-Topaz1" target="_blank">[6]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043205#pone.0043205-Yancovitch1" target="_blank">[18]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043205#pone.0043205-Dumitrescu1" target="_blank">[19]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043205#pone.0043205-Frishberg1" target="_blank">[24]</a>. The location of the ENU-induced mouse TCAL Trp589Arg mutation, which involved an evolutionary conserved Trp (W) residue (Fig. 3D), within the carbohydrate-binding domain, is shown relative to <i>GALNT3</i> mutations identified in man.