TTRMDb
An amyloid disease database for transthyretin mutants
Sequence
| Analysis Tool |
Result |
| iMutant 3.0 | Destabilizing |
| STRUM | Stabilizing |
| iStable | Destabilizing |
| Provean | Deleterious |
| PredictSNP | Neutral |
| PhD-SNP | Deleterious |
| PolyPhen-2 | Neutral |
| SIFT | Neutral |
| FATHMM | Damaging |
Structure
| Analysis Tool |
Result |
| mCSM | Destabilizing |
| SDM | Destabilizing |
| 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
- Altland K, Benson MD, Costello CE, Ferlini A, Hazenberg BPC, Hund E, et al. Genetic microheterogeneity
of human transthyretin detected by IEF. ELECTROPHORESIS. 2007;28: 2053–2064.
doi:10.1002/elps.200600840
- Wallace MR, Dwulet FE, Conneally PM, and Benson MD. (1986). Biochemical and molecular genetic
characterization of a new variant prealbumin associated with hereditary amyloidosis. J Clin Invest. 78:6-12.
- Refetoff S, Dwulet FE, and Benson MD. (1986). Reduced affinity for thyroxine in two of three structural
thyroxine-binding prealbumin variants associated with familial amyloidotic polyneuropathy. J Clin Endocrinol
Metab. 63(6):1432-1437.
- Benson MD, Wallace MR, Tejada E, Beumann H, and Page B. (1987). Description of a new American
kindred with late onset cardiomyopathy. Arthritis Rheum. 30:195-200.
- Koeppen AH, Wallace MR, Benson MD, and Altland K. (1990). Familial amyloid polyneuropathy: Alanine-for
-threonine substitution in the transthyretin (prealbumin) molecule. Muscle Nerve. 13:1065.
- Staunton H, Davis MB, Guiloff RJ, Nakazato M, Miyazato N, and Harding AE. (1991). Irish (Donegal)
amyloidosis is associated with the transthyretin ALA60 (Appalachian) variant. Brain. 114:2675-2679.
Studies on Therapeutic Strategy*
- 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
- Merlini G, Planté-Bordeneuve V, Judge DP, Schmidt H, Obici L, Perlini S, et al.
Effects of Tafamidis on Transthyretin Stabilization and Clinical Outcomes in
Patients with Non-Val30Met Transthyretin Amyloidosis. J Cardiovasc Transl Res.
2013;6: 1011–1020. doi:10.1007/s12265-013-9512-x
- Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, et
al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis.
N Engl J Med. 2018;379: 22–31. doi:10.1056/NEJMoa1716793
- 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
*includes studies on model organisms and commercially unavailable drugs
Available PDB Structures