Sequence

Analysis Tool	Result
iMutant 3.0	Stabilizing
STRUM	Stabilizing
iStable	Destabilizing
Provean	Deleterious
PredictSNP	Deleterious
PhD-SNP	Deleterious
PolyPhen-2	Deleterious
SIFT	Deleterious
FATHMM	Damaging

Structure

Analysis Tool	Result
mCSM	Destabilizing
SDM	Stabilizing
DUET	Destabilizing
DynaMut	Destabilizing
CUPSAT	Stabilizing
ENCoM	Destabilizing
FoldX (Protein Stability)	No effect

Aggregation

Analysis Tool	Result
TANGO (Aggregation Tendency)	No effect
WALTZ (Amyloid Propensity)	No effect
LIMBO (Chaperone Binding Tendency)	No effect

Reported Articles

• Karlsson A, Olofsson A, Eneqvist T, Sauer-Eriksson AE. Cys114-Linked Dimers of Transthyretin Are Compatible with Amyloid Formation,. Biochemistry. 2005;44: 13063–13070. doi:10.1021/bi050795s
• Ueno S, Uemichi T, Yorifuji S, and Tarui S. (1990). A novel variant of transthyretin (Tyr114 to Cys) deduced from the nucleotide sequences of gene fragments from familial amyloidotic polyneuropathy in Japanese sibling cases. Biochem Biophys Res Commun. 169:143-147
• Uemichi T, Ueno S, Takahashi N, Soga F, Yorifuji S, and Tarui S. (1991). DNA tests for mutant genes coding for transthyretins Gly42, Arg50, and Cys114 in Japanese cases of familial amyloid polyneuropathy. Rinsho Shinikeigaku. 31:1151-1154
• Ueno S, Fujimura H, Yorifuji S, Nakamura Y, Takahashi M, Tarui S, and Yanagihara T. (1992). Familial amyloid polyneuropathy associated with the transthyretin cys114 gene in a Japanese kindred. Brain. 115:1275-1289
• Ando Y, Almeida M, Ohlsson PI, Ando E, Negi A, Suhr O, Terazaki H, Obayashi K, Ando M and Saraiva MJ. (1999). Unusual self-association properties of transthyretin Y114C related to familial amyloidotic polyneuropathy: effects on detection and quantitiation. Biochem Biophys Res Commun. 261:264-269
• Ando Y, Yamashia T, Ando E, Terazaki H, Obayashi K, Fujise N, Ohlsson P-I, Suhr OB, Negi A, Ando M, and Miyakawa T. (1999). Analysis of vitreous amyloid of patients with familial amyloidotic polyneuropathy (FAP ATTR Tyr114Cys) The 4th Int’l Symp on FAP and Other TTR Related Disorders. Umeå Sweden, June 1999

Studies on Therapeutic Strategy*

• Adams D, Gonzalez-Duarte A, O’Riordan WD, Yang C-C, Ueda M, Kristen AV, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018;379: 11–21. doi:10.1056/NEJMoa1716153
• Tojo K, Sekijima Y, Kelly JW, Ikeda S. Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis. Neuroscience Research. 2006;56: 441–449. doi:10.1016/j.neures.2006.08.014

*includes studies on model organisms and commercially unavailable drugs

Available PDB Structures

• 1III