Table 1.

Summary of TTR variants stability, cellular distribution and ERAD efficiency

TTR variant	Phenotype	Character	Monomer TTR (%) T4 (1 μM)	Monomer TTR (%) diflunisal (1 μM)	Cellular localization	Intracellular protein (%) (6 h treatment)
						CHX	CHX+MG132
WT		SSA	12.2±0.8	20.3±3.4	ER and Golgi	9.1±1.3	11.6±0.7
R104Ha	Non-amyloid	Low suppressive effect	6.1±0.9	1.0±2.6	ER and Golgi
T119Ma	Non-amyloid	Suppresive effect	ND	ND	ER and Golgi
D18G	CNS, LM	Largely monomeric form, late onset	ND	ND	ER	11.2±1.0	42.0±6.5*
A25T	CNS, PN	Unstable tetramer, late onset	83.1±9.5	92.2±4.3	ER and Golgi
V30M	AN, E, LM, PN	Prevalent, mild progression	43.4±3.3	58.3±3.4	ER and Golgi	10.0±0.6	15.1±0.3**
E54K	AN, H, PN	Aggressive progression	92.2±4.9	96.6±1.4	ER and Golgi
L55P	AN, E, H, PN	Aggressive progression	61.5±2.6	85.3±2.6	ER and Golgi
Monomeric mutant
Wild type					ER and Golgi	9.5±0.2	9.7±0.1
R104H					ER and Golgi	8.4±1.1	9.4±0.6
T119M					ER and Golgi	7.8±0.5	8.8±0.4
D18G					ER	11.1±1.3	77.2±6.1***
A25T					ER	8±0.3	58.0±6.8*
V30M					ER	8.8±0.6	26.2±3.3**
E54K					ER	12.3±0.0	20.9±0.3***
L55P					ER	12.1±1.0	29.1±1.9**
Abbreviations: AN, autonomic neuropathy; CNS, central nervous system; CTS, carpal tunnel syndrome; E, eye; H, heart; LM, leptomeningeal; PN, polyneuropathy; S, skin.
aNon-amyloidogenic variant.
Monomer TTR (%)=100 × (non-reduced and non-boiled monomer at 1 μM T4 or diflunisal/reduced and boiled monomer at 0 μM T4 or diflunisal)
ND: not detected. *P<0.05, **P<0.01 and ***P<0.001.