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
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