It was seen that the BIRC6 SNP was not covered in the maps used in those studies therefore that might be the reason of not finding rs275411 association. Contrary to the studies mentioned above we and Carbone et al found significant association of the SNP with PEXG and POAG respectively. As SNPs have individual, ethnicity and population specific role in disease etiology, therefore the association that we found could be due to divergent background of the studied populations. In conclusion, our study demonstrates that the T allele of the rs2754511 in the BIRC6 gene plays a protective role in PEXG patients of the Pakistani population. This supports a role for the UPR pathway and regulation of apoptotic cell death in the pathogenesis of PEXG. The highest amino acid homology to the unknown domain of CcSDH was obtained with Deinococcus radiodurans L-sorbosone dehydrogenase. Glucose dehydrogenase and sorbosone dehydrogenase, which have the highest degree of similarity to this protein, are both Homatropine Bromide PQQ-dependent dehydrogenases. The catalytic activity for various sugars was observed only in the presence of PQQ. The strong binding activity of the protein to PQQ was shown by ITC. Based on these findings, we concluded that CcSDH is a PQQ-dependent enzyme, even though it shows low amino acid Tubeimoside-I sequence homology with known PQQ-dependent enzymes. The three-dimensional structures of PQQ-dependent quinoproteins are generally divided into two types: an eight-bladed betapropeller structure with each blade consisting of a four-stranded anti-parallel beta-sheet, and a six-bladed beta-propeller structure. These two types of enzymes have no amino acid sequence homology with each other. The three-dimensional structure of CcSDH was modeled using the Phyre2 protein fold recognition server and the predicted structure was compared with those of other quinoproteins and structurally similar proteins. CcSDH was predicted to have a six-bladed instead 
of an eight-bladed quinoprotein structure. As shown in Table 2, CcSDH shows some structural homology with known prokaryote PQQdependent sugar dehydrogenases, sGDH and soluble aldose sugar dehydrogenases from Pyrobaculum aerophilum and Escherichia coli, although the amino acid sequence homology is low. Among prokaryotic sugar dehydrogenases, CcSDH shows some structural similarity with human hedgehog-interacting protein. As seen in the alignment of the amino acid sequence of CcSDH with those of known six-bladed quinoproteins, a putative catalytic histidine is conserved in all proteins, whereas several amino acids contributing to PQQ binding in the prokaryote sugar dehydrogenase are missing in CcSDH and HHIP. However, as demonstrated above, the activity of CcSDH is PQQ-dependent. Thus, the amino acids involved in the adsorption of PQQ should be different in this enzyme family, indicating the diversity of PQQbinding motifs in eukaryotic enzymes. The PQQ-dependent sugar dehydrogenase that we discovered here has interesting enzymatic properties associated with characteristic cytochrome and cellulose-binding domains as well as the enzymes related to plant cell wall degradation, and shows high activity towards rare sugars. Therefore, the discovery of the PQQ-dependent domain in CcSDH could form the basis for a new AA family in the CAZy database. Detailed enzymatic studies will be necessary to evaluate why eukaryotes produce and secrete such enzymes, and how these enzymes acquire PQQ, because only a few prokaryotic organisms has been reported to be capable of synthesizing PQQ.