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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 147 | 18q12.1 | TTR | transthyretin | |
| Mouse | - | 147 | 18 11.47 cM | Ttr | transthyretin | |
| Rat | - | 147 | 18p12 | Ttr | transthyretin | |
| Previous and Unofficial Names |
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| carpal tunnel syndrome 1 [4] | CTS1 | PALB | prealbumin, amyloidosis type I | |
| Database Links |
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| Alphafold | P02766 (Hs), P07309 (Mm), P02767 (Rn) |
| CATH/Gene3D | 2.60.40.180 |
| ChEMBL Target | CHEMBL3194 (Hs), CHEMBL2151 (Rn) |
| Ensembl Gene | ENSG00000118271 (Hs), ENSMUSG00000061808 (Mm), ENSRNOG00000016275 (Rn) |
| Entrez Gene | 7276 (Hs), 22139 (Mm), 24856 (Rn) |
| Human Protein Atlas | ENSG00000118271 (Hs) |
| KEGG Gene | hsa:7276 (Hs), mmu:22139 (Mm), rno:24856 (Rn) |
| OMIM | 176300 (Hs) |
| Pharos | P02766 (Hs) |
| RefSeq Nucleotide | NM_000371 (Hs), NM_013697 (Mm), NM_012681 (Rn) |
| RefSeq Protein | NP_000362 (Hs), NP_038725 (Mm), NP_036813 (Rn) |
| SynPHARM | 82072 (in complex with tafamidis) |
| UniProtKB | P02766 (Hs), P07309 (Mm), P02767 (Rn) |
| Wikipedia | TTR (Hs) |
| Selected 3D Structures |
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Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Immuno Process Associations | ||
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| Clinically-Relevant Mutations and Pathophysiology
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| Gene Expression and Pathophysiology Comments | |
| Excess production and accumulation of transthyretin (TTR) causes hereditary transthyretin-mediated amyloidosis. Drugs that directly inhibit TTR expression (of both wild type and mutant TTR) in the liver, are now approved for use in clinical practice. |
| General Comments |
| Three drugs that disrupt TTR expression have been approved for clinical use, as a mechanism to treat hereditary transthyretin-mediated amyloidosis: inotersen (Tegsedi®) is an antisense oligonucleotide, and patisiran (Onpattro®) and vutrisiran (Amvuttra®) are double-stranded small interfering RNAs. As an alternative gene-level intervention, Intellia Therapeutics have conducted a first-in-human trial of their in vivo CRISPR/Cas9 TTR genome editing candidate, NTLA-2001 (NCT04601051) [6]. NTLA-2001 reduced serum levels of transthyretin. The orally administered, small molecule TTR stabilising drug tafamidis is authorised for the treament of transthyretin amyloid cardiomyopathy (ATTR-CM), with others such as acoramidis (AG10; BridgeBio) in development [3]. TTR stabilisers inhibit dissociation of the tetrameric protein complex into the monomeric units that can misfold and accumulate as TTR amyloid deposits. |
1. Benson MD. (1991) Inherited amyloidosis. J Med Genet, 28 (2): 73-8. [PMID:1848299]
2. Bulawa CE, Connelly S, Devit M, Wang L, Weigel C, Fleming JA, Packman J, Powers ET, Wiseman RL, Foss TR et al.. (2012) Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc Natl Acad Sci USA, 109 (24): 9629-34. [PMID:22645360]
3. Gillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, Grogan M, Hanna M, Hoffman J, Masri A et al.. (2024) Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med, 390 (2): 132-142. [PMID:38197816]
4. Murakami T, Tachibana S, Endo Y, Kawai R, Hara M, Tanase S, Ando M. (1994) Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant. Neurology, 44 (2): 315-8. [PMID:8309582]
5. Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, Rappley I, Vogel H, Liedtke M, Witteles RM et al.. (2013) AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc Natl Acad Sci USA, 110 (24): 9992-7. [PMID:23716704]
6. Yadav JD, Othee H, Chan KA, Man DC, Belliveau PP, Towle J. (2021) Transthyretin Amyloid Cardiomyopathy-Current and Future Therapies. Ann Pharmacother, 55 (12): 1502-1514. [PMID:33685242]
Transthyretin: transthyretin. Last modified on 16/09/2024. Accessed on 07/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2851.
