Supplementary Table 1 | Genetic disorders caused by abnormal proteostasis and ER stress. Gene mutations can either cause defective protein folding, resulting in loss of function or toxicity due to accumulation of the mutant protein in the ER; or impair protein folding and trafficking, leading to abnormal proteostasis and ER stress. Some gene mutations that cause human genetic disorders are summarized in the table. Mutations in glycosyltransferases are not included because they were recently reviewed189. Mechanisms Gene mutations cause defective protein folding, resulting in loss of function or toxicity due to accumulation of the mutant protein in the ER. Mutated Genes α-galactosidase A α-synuclein α-1 antitrypsin β-amyloid peptide β-glucocerebrosidase Carbonic anhydrase IV Cationic trypsinogen Clotting factor VIII Clotting factor IX Cystic fibrosis transmembrane conductance regulator Desmoglein 4 Insulin Related Diseases Fabry’s disease Parkinson’s disease Emphysema with possible liver failure Alzheimer’s disease Gaucher’s disease Retinitis pigmentosa Hereditary pancreatitis Haemophilia A Hemophilia B Cystic fibrosis References 126 78,127 128-130 74,131 132 133,134 135 136,137 138 139,140 Monilethrix Mutant Ins-gene-induced Diabetes of Youth Retinitis pigmentosa 141 142,143 Primary open-angle glaucoma Severe congenital neutropenia 145-147 148,149 Palmitoyl-protein thioesterase-1 Parkin Peripheral myelin protein 22 Preproparathyroid hormone Protein kinase C gamma Proteolipid protein 1 Seipin Superoxide dismutase 1 Neurodegenerative diseases Parkinson’s disease Charcot-Marie-Tooth syndrome Familial isolated hypoparathyroidism Spinocerebellar ataxia type 14 Pelizaeus-Merzbacher disease Neurodegenerative diseases Amyotrophic lateral sclerosis 150,151 152,153 154,155 156 157 158,159 160-163 164-166 Synaptic cell adhesion molecule-1 Tissue-specific extracellular matrices Thyroglobulin Autism spectrum disorder Connective tissue diseases 167 168 Autosomal recessive congenital hypothyroidism Neurodegenerative diseases Amyotrophic lateral sclerosis 169,170 Achromatopsia Myeloproliferative neoplasia Joubert syndrome 46 174 175 Sever hypertriglyceridemia 72 Darier's disease Combined deficiency of 176,177 61,178 Interphotoreceptor retinoidbinding protein Myocilin Neutrophil elastase Gene mutations impair protein folding and trafficking, leading to abnormal proteostasis and ER stress. Valosin-containing protein Vesicle-associated membrane protein-associated protein B ATF6α Calreticulin Centrosomal protein nephrocystin-6 Cyclic-AMP-responsive-elementbinding protein H ER Ca2+ ATPase ATP2A2 Lectin mannose-binding 1 / 1 144 171 172,173 Multiple coagulation factor deficiency protein 2 Protein disulfide isomerase PERK Rhodopsin Sil1/Bap (BiP exchange factor) Clotting factors V and VIII Amyotrophic lateral sclerosis Wolcott-Rallison syndrome Retinitis pigmentosa Marinesco-Sjorgren syndrome 179 33,58 180,181 182,183 The site-2 protease Skin defects Neurodegenerative diseases Wolfram syndrome 184 Wolfram syndrome 1 185-188 References 126 Yam, G. H., Zuber, C. & Roth, J. A synthetic chaperone corrects the trafficking defect and disease phenotype in a protein misfolding disorder. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19, 12-18, doi:10.1096/fj.04-2375com (2005). 127 Cooper, A. A. et al. 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