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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
TTR is a homo-tetrameric protein which transports thyroxine in the plasma and cerebrospinal fluid and retinol (vitamin A) in the plasma. Many disease causing mutations in the protein have been reported, many of which cause complex dissociation and protein mis-assembly and deposition of toxic aggregates amyloid fibril formation . These amyloidogenic mutants are linked to the development of pathological amyloidoses, including familial amyloid polyneuropathy (FAP) [1-2], familial amyloid cardiomyopathy (FAC) , amyloidotic vitreous opacities, carpal tunnel syndrome  and others. In old age, non-mutated TTR can also form pathological amyloid fibrils . Pharmacological intervention to reduce or prevent TTR dissociation is being pursued as a theapeutic strategy. To date one small molecule kinetic stabilising molecule (tafamidis) has been approved for FAP, and is being evaluated in clinical trials for other TTR amyloidoses.
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2. Coelho T. (1996) Familial amyloid polyneuropathy: new developments in genetics and treatment. Curr. Opin. Neurol., 9 (5): 355-9. [PMID:8894411]
3. Jacobson DR, Pastore RD, Yaghoubian R, Kane I, Gallo G, Buck FS, Buxbaum JN. (1997) Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans. N. Engl. J. Med., 336 (7): 466-73. [PMID:9017939]
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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. U.S.A., 110 (24): 9992-7. [PMID:23716704]
7. Westermark P, Shirahama T, Skinner M, Norén P, Cohen AS. (1981) Amyloid P-component (protein AP) in localized amyloidosis as revealed by an immunocytochemical method. Histochemistry, 71 (2): 171-5. [PMID:7016817]
Database page citation:
Carrier proteins. Accessed on 27/03/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=911.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Buneman OP, Catterall WA, Cidlowski JA, Davenport AP, Fabbro D, Fan G, McGrath JC, Spedding M, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Overview. Br J Pharmacol. 172: 5729-5743.