TTRMDb
An amyloid disease database for transthyretin mutants
Sequence
| Analysis Tool |
Result |
| iMutant 3.0 | Destabilizing |
| STRUM | Destabilizing |
| iStable | Destabilizing |
| Provean | Deleterious |
| PredictSNP | Deleterious |
| PhD-SNP | Deleterious |
| PolyPhen-2 | Deleterious |
| SIFT | Deleterious |
| FATHMM | Damaging |
Structure
| Analysis Tool |
Result |
| mCSM | Destabilizing |
| SDM | Destabilizing |
| DUET | Destabilizing |
| DynaMut | Destabilizing |
| CUPSAT | Destabilizing |
| ENCoM | Destabilizing |
| FoldX (Protein Stability) | Reduces |
Aggregation
| Analysis Tool |
Result |
| TANGO (Aggregation Tendency) | No effect |
| WALTZ (Amyloid Propensity) | No effect |
| LIMBO (Chaperone Binding Tendency) | No effect |
Reported Articles
- Nichols WC, Liepnieks JJ, McKusick VA, and Benson MD. (1989). Direct sequencing of the gene for
Maryland/German familial amyloidotic polyneuropathy type II and genotyping by allele-specific enzymatic
amplification. Genomics. 5:535-540.
- Mahloudji M, Teasdall RD, Adamkiewicz JJ, Hartmann WH, Lambird PA, and McKusick VA. (1969).
The genetic amyloidoses. With particular reference to hereditary neuropathic amyloidosis,
type (Indiana or Rukavina type) Medicine. 48:1-37.
- Mendell JR, Jiang X-S, Warmolts JR, Nichols WC, and Benson MD. (1990). Diagnosis of Maryland/German
familial amyloidotic polyneuropathy using allele-specific, enzymatically amplified genomic DNA.
Ann Neurol. 27:553-557.
- Jacobson DR, Gorevic PD, Sack GH, and Malamet RL. (1993). Homozygous transthyretin His 58
associated with unusually aggressive familial amyloidotic polyneuropathy. J Rheumatol. 20:178.
- Zhao N, Aoyama N, Benson MD, Skinner M, Satier F, and Sakaki Y. (1994). Haplotype analysis of His58,
Ala60, and Tyr77 types of familial amyloidotic polyneuropathy. Amyloid: Int J Exp Clin Invest. 1:75-79.
- Goebel HH, Seddigh S, Hopf HC, Uemichi T, Benson MD, and McKusick VA. (1997) A European family with
histidine 58 transthyretin mutation in familial amyloid polyneuropathy. Neuromuscul Disord. 7:229-230.
Studies on Therapeutic Strategy*
- 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
- 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
- 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
*includes studies on model organisms and commercially unavailable drugs
Available PDB Structures