Top ▲


Click here for help

Target not currently curated in GtoImmuPdb

Target id: 2851

Nomenclature: transthyretin

Abbreviated Name: TTR

Family: Transthyretin

Gene and Protein Information Click here for help
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 Click here for help
carpal tunnel syndrome 1 [5] | CTS1 | PALB | prealbumin, amyloidosis type I
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of wild-type TTR in complex with tafamidis.
Ligand:  tafamidis
Resolution:  1.3Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  The Structure of V122I Mutant Transthyretin in Complex with Tafamidis
Ligand:  tafamidis
Resolution:  1.2Å
Species:  Human
References:  6

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
tafamidis Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 8.7 pKd 2
pKd 8.7 (Kd 2x10-9 M) [2]
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Familial amyloid cardiomyopathy
Description: Familial amyloid cardiomyopathy (FAP) is a degenerative disease caused by the formation of transthyretin (TTR) amyloidogenic fibrils in the heart.
Synonyms: Transthyretin amyloid cardiopathy
Transthyretin amyloidosis [Disease Ontology: DOID:0050638]
Transthyretin-related familial amyloid cardiomyopathy [Orphanet: ORPHA85451]
TTR-related cardiac amyloidosis
Disease Ontology: DOID:0050638
OMIM: 105210
Orphanet: ORPHA85451
References:  2
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human V30M 148G>A 1
Missense Human V122I 6
Gene Expression and Pathophysiology Comments
Excess production and accumulation of transthyretin (TTR) causes hereditary transthyretin-mediated amyloidosis. Two novel drugs are now approved to combat this disease: inotersen (Tegsedi®) [4] and patisiran (Onpattro®) [3]. Both of these drugs act to reduce the amount of TTR protein (both wild type and mutant) produced in the liver, but by slightly different mechanisms. Inotersen is an antisense oligonucleotide inhibitor of TTR synthesis, whereas patisiran is a double-stranded small interfering RNA (which targets a conserved sequence in the 3' UTR of mutant and wild-type TTR mRNA). Inotersen is administered subcutaneously, and patisiran is delivered by intravenous infusion in a lipid nanoparticle formulation.
General Comments
As an alternative to the two approved drugs that disrupt TTR expression as a mechanisn to treat hereditary transthyretin-mediated amyloidosis (inotersen, an antisense oligonucleotide and patisiran, a double-stranded small interfering RNA), Intellia Therapeutics have conducted a first-in-human trial of their in vivo CRISPR/Cas9 TTR genome editing candidate, NTLA-2001 (NCT04601051) [7]. NTLA-2001 reduced serum levels of transthyretin.


Show »

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. Hoy SM. (2018) Patisiran: First Global Approval. Drugs, 78 (15): 1625-1631. [PMID:30251172]

4. Keam SJ. (2018) Inotersen: First Global Approval. Drugs, 78 (13): 1371-1376. [PMID:30120737]

5. 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]

6. 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]

7. Yadav JD, Othee H, Chan KA, Man DC, Belliveau PP, Towle J. (2021) Transthyretin Amyloid Cardiomyopathy-Current and Future Therapies. Ann Pharmacother,: 10600280211000351 [Epub ahead of print]. DOI: 10.1177/10600280211000351 [PMID:33685242]

How to cite this page

Transthyretin: transthyretin. Last modified on 29/06/2021. Accessed on 25/03/2023. IUPHAR/BPS Guide to PHARMACOLOGY,