Gene: TTR

Alternate names for this Gene: ATTR|CTS|CTS1|HEL111|HsT2651|PALB|TBPA

Gene Summary: This gene encodes one of the three prealbumins, which include alpha-1-antitrypsin, transthyretin and orosomucoid. The encoded protein, transthyretin, is a homo-tetrameric carrier protein, which transports thyroid hormones in the plasma and cerebrospinal fluid. It is also involved in the transport of retinol (vitamin A) in the plasma by associating with retinol-binding protein. The protein may also be involved in other intracellular processes including proteolysis, nerve regeneration, autophagy and glucose homeostasis. Mutations in this gene are associated with amyloid deposition, predominantly affecting peripheral nerves or the heart, while a small percentage of the gene mutations are non-amyloidogenic. The mutations are implicated in the etiology of several diseases, including amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia, amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis and carpal tunnel syndrome.

Gene is located in Chromosome: 18

Location in Chromosome : 18q12.1

Description of this Gene: transthyretin

Type of Gene: protein-coding

rs104894665 in TTR gene and AMYLOIDOSIS, HEREDITARY, TRANSTHYRETIN-RELATED PMID 3818577 1986 Analyses of prealbumin mRNAs in individuals with familial amyloidotic polyneuropathy.

PMID 25173338 2014 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).

PMID 2891727 1988 Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis.

PMID 7850982 1995 A novel variant of transthyretin, 59Thr-->Lys, associated with autosomal dominant cardiac amyloidosis in an Italian family.

PMID 8019560 1994 "A double-variant transthyretin allele (Ser 6, Ile 33) in the Israeli patient ""SKO"" with familial amyloidotic polyneuropathy."

PMID 1570831 1992 A new transthyretin mutation associated with amyloid cardiomyopathy.

PMID 17503405 2007 Genetic microheterogeneity of human transthyretin detected by IEF.

PMID 12050338 2002 Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis.

PMID 1351039 1992 Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse amyloidosis with cardiac and neurologic involvement.

PMID 24368466 2013 Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial.

PMID 12403615 2002 Disulfide-bond formation in the transthyretin mutant Y114C prevents amyloid fibril formation in vivo and in vitro.

PMID 10439117 1999 A new transthyretin variant (Ser23Asn) associated with familial amyloidosis in a Portuguese patient.

PMID 17453626 2007 A new transthyretin variant (Glu61Gly) associated with cardiomyopathy.

PMID 9066351 1997 Transthyretin amyloidosis: a new mutation associated with dementia.

PMID 15214015 2004 A severe form of amyloidotic polyneuropathy in a Costa Rican family with a rare transthyretin mutation (Glu54Lys).

PMID 10436378 1999 Identification of a new transthyretin variant (Ile49) in familial amyloidotic polyneuropathy using electrospray ionization mass spectrometry and nonisotopic RNase cleavage assay.

PMID 11445644 2001 Recurrent subarachnoid hemorrhage associated with a new transthyretin variant (Gly53Glu).

PMID 16185074 2005 Cys114-linked dimers of transthyretin are compatible with amyloid formation.

PMID 10611950 1999 Usefulness of MALDI/TOF mass spectrometry of immunoprecipitated serum variant transthyretin in the diagnosis of familial amyloid polyneuropathy.

PMID 2161654 1990 A novel variant of transthyretin (Tyr114 to Cys) deduced from the nucleotide sequences of gene fragments from familial amyloidotic polyneuropathy in Japanese sibling cases.

PMID 10211412 1999 A new amyloidogenic transthyretin variant (Val122Ala) found in a compound heterozygous patient.

PMID 10071047 1999 Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis.

PMID 24650283 2014 Clinical proteome informatics workbench detects pathogenic mutations in hereditary amyloidoses.

PMID 7643356 1995 A new transthyretin variant (Ser 24) associated with familial amyloid polyneuropathy.

PMID 27724962 2016 Endomyocardial biopsy in patients with cardiomyopathy of unknown origin: does specialized center experience apply to a tertiary care hospital?

PMID 26656838 2016 Survival After Transplantation in Patients With Mutations Other Than Val30Met: Extracts From the FAP World Transplant Registry.

PMID 25526974 2015 In vivo detection of nerve injury in familial amyloid polyneuropathy by magnetic resonance neurography.

PMID 25743445 2015 Cardiac findings and events observed in an open-label clinical trial of tafamidis in patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis.

PMID 20209591 2010 Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience.

PMID 2613237 1989 Direct sequencing of the gene for Maryland/German familial amyloidotic polyneuropathy type II and genotyping by allele-specific enzymatic amplification.

PMID 9196903 1997 A European family with histidine 58 transthyretin mutation in familial amyloid polyneuropathy.

PMID 14968122 2004 Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants.

PMID 19602727 2009 Amyloidogenic potential of transthyretin variants: insights from structural and computational analyses.

PMID 9748569 1998 A simple screening test for variant transthyretins associated with familial transthyretin amyloidosis using isoelectric focusing.

PMID 15820680 2005 The biological and chemical basis for tissue-selective amyloid disease.

PMID 15185492 2004 Amyloidogenic and anti-amyloidogenic properties of recombinant transthyretin variants.

PMID 14640030 2003 Tabulation of human transthyretin (TTR) variants, 2003.

PMID 12000195 2002 Transthyretin Thr60Ala Appalachian-type mutation in a Japanese family with familial amyloidotic polyneuropathy.

PMID 7608709 1995 Familial amyloid polyneuropathy (TTR ala 60) in north west Ireland: a clinical, genetic, and epidemiological study.

PMID 11385707 2001 Transthyretin mutations in hyperthyroxinemia and amyloid diseases.

PMID 25997029 2015 Differential Myocyte Responses in Patients with Cardiac Transthyretin Amyloidosis and Light-Chain Amyloidosis: A Cardiac MR Imaging Study.

PMID 4079954 1986 Familial amyloid polyneuropathy.

PMID 3030336 1987 Hereditary amyloidosis: description of a new American kindred with late onset cardiomyopathy. Appalachian amyloid.

PMID 3097057 1986 Reduced affinity for thyroxine in two of three structural thyroxine-binding prealbumin variants associated with familial amyloidotic polyneuropathy.

PMID 21992998 2012 Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant.

PMID 2122246 1990 Familial amyloid polyneuropathy: alanine-for-threonine substitution in the transthyretin (prealbumin) molecule.

PMID 26017327 2015 Hereditary ATTR amyloidosis: a single-institution experience with 266 patients.

PMID 7656439 1995 Low plasma concentrations of retinol-binding protein in individuals with mutations affecting position 84 of the transthyretin molecule.

PMID 9818054 1998 Tertiary structures of amyloidogenic and non-amyloidogenic transthyretin variants: new model for amyloid fibril formation.

PMID 3722385 1986 Biochemical and molecular genetic characterization of a new variant prealbumin associated with hereditary amyloidosis.

PMID 7655883 1995 Transthyretin gene analysis in European patients with suspected familial amyloid polyneuropathy.

PMID 9771673 1998 Transthyretin Tyr77 familial amyloid polyneuropathy: a clinicopathological study of a large kindred.

PMID 8509786 1993 Transthyretin gene mutations in British and French patients with amyloid neuropathy.

PMID 26369527 2015 Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France.

PMID 1997217 1991 A new transthyretin variant from a patient with familial amyloidotic polyneuropathy has asparagine substituted for histidine at position 90.

PMID 1981182 1990 Diagnosis of familial amyloidotic polyneuropathy in France.

PMID 9547003 1998 Transthyretin mutation (serine 84) associated with familial amyloid polyneuropathy in a Hungarian family.

PMID 2840822 1988 A DNA test for Indiana/Swiss hereditary amyloidosis (FAP II).

PMID 3760189 1986 Characterization of a transthyretin (prealbumin) variant associated with familial amyloidotic polyneuropathy type II (Indiana/Swiss).

PMID 23713495 2013 Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis.

PMID 21135536 2011 Transthyretin-related hereditary amyloidosis in a Chinese family with TTR Y114C mutation.

PMID 20686303 2010 A case of atypical amyloid polyneuropathy with predominant upper-limb involvement with the diagnosis unexpectedly found at lung operation.

PMID 15123043 2003 The hereditary amyloidoses.

PMID 11940682 2002 Familial transthyretin-type amyloid polyneuropathy in Japan: clinical and genetic heterogeneity.

PMID 2363717 1990 Two novel variants of transthyretin identified in Japanese cases with familial amyloidotic polyneuropathy: transthyretin (Glu42 to Gly) and transthyretin (Ser50 to Arg).

PMID 22928869 2012 Familial amyloidosis with polyneuropathy associated with TTR Ser50Arg mutation.

PMID 24053266 2013 Description of transthyretin S50A, S52P and G47A mutations in familial amyloidosis polyneuropathy.

PMID 22745357 2013 Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective.

PMID 17577688 2007 Familial amyloid polyneuropathy associated with TTRSer50Arg mutation in two Iberian families presenting a novel single base change in the mutant gene.

PMID 1335038 1992 Amyloid polyneuropathy with transthyretin Arg50 in a Japanese case from Osaka.

PMID 16357452 2005 Ten years of experience with liver transplantation for familial amyloid polyneuropathy in Japan: outcomes of living donor liver transplantations.

PMID 16530227 2006 Diffuse metabolic changes in the brain of patients with familial amyloid polyneuropathy. A proton MRSI study.

PMID 24767411 2014 THAOS: gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease.

PMID 27858761 2015 Transthyretin-Related Familial Amyloid Polyneuropathy (TTR-FAP): A Single-Center Experience in Sicily, an Italian Endemic Area.

PMID 24073013 2013 Comparison of cardiac amyloidosis due to wild-type and V122I transthyretin in older adults referred to an academic medical center.

PMID 27238058 2016 Genotypic and phenotypic presentation of transthyretin-related familial amyloid polyneuropathy (TTR-FAP) in Turkey.

PMID 22747647 2013 Diflunisal for ATTR cardiac amyloidosis.

PMID 15110620 2004 Combined heart and liver transplantation in four adults with familial amyloidosis: experience of a single center.

PMID 1362222 1992 A new mutant transthyretin (Arg 10) associated with familial amyloid polyneuropathy.

PMID 14695346 2004 Cysteine 10 is a key residue in amyloidogenesis of human transthyretin Val30Met.

PMID 19372189 2009 SELDI-TOF mass spectrometry evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy.

PMID 14640031 2003 Atypical familial motor neuropathy in patients with mutant TTR Ile68Leu.

PMID 21540676 2011 Asymptomatic homozygous gene carrier in a family with Ile68Leu ATTR amyloidosis: a new endemic region in northern Tuscany?

PMID 28635949 2017 Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis.

PMID 26537620 2016 Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness.

PMID 1786038 1992 Transthyretin Leu 68 in a form of cardiac amyloidosis.

PMID 8038017 1993 Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant.

PMID 12039669 2002 Transthyretin Val 107 in a Japanese patient with familial amyloid polyneuropathy.

PMID 19781421 2009 Cardiac amyloidosis in African Americans: comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis.

PMID 9748014 1998 Genotypic-phenotypic variations in a series of 65 patients with familial amyloid polyneuropathy.

PMID 8081397 1994 Transthyretin VAL107, a new variant associated with familial cardiac and neuropathic amyloidosis.

PMID 24480837 2014 Multimodal retinal imaging in a Chinese kindred with familial amyloid polyneuropathy secondary to transthyretin Ile107Met mutation.

PMID 7914929 1994 Amyloid polyneuropathy in two German-American families: a new transthyretin variant (Val 107).

PMID 27584576 2016 Evaluation of Therapeutic Oligonucleotides for Familial Amyloid Polyneuropathy in Patient-Derived Hepatocyte-Like Cells.

PMID 26428663 2016 The Val142Ile transthyretin cardiac amyloidosis: not only an Afro-American pathogenic variant? A single-centre Italian experience.

PMID 2046936 1991 Two-tiered DNA-based diagnosis of transthyretin amyloidosis reveals two novel point mutations.

PMID 8721565 1996 Homozygosity and heterozygosity for the transthyretin Leu64 mutation: clinical, biochemical and molecular findings.

PMID 22592564 2013 TTR-related amyloid neuropathy: clinical, electrophysiological and pathological findings in 15 unrelated patients.

PMID 23279339 2012 Transthyretin-related familial amyloidotic polyneuropathy: description of a cohort of patients with Leu64 mutation and late onset.

PMID 24184229 2014 Homozygosity for the V122I mutation in transthyretin is associated with earlier onset of cardiac amyloidosis in the African American population in the seventh decade of life.

PMID 9191784 1997 A trinucleotide deletion in the transthyretin gene (delta V 122) in a kindred with familial amyloidotic polyneuropathy.

PMID 11140845 2000 Familial amyloid polyneuropathy in a Spanish family with a transthyretin deletion (deltaVal 122) presenting with carpal tunnel syndrome.

PMID 8579098 1996 Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G)

PMID 8960746 1996 Familial meningocerebrovascular amyloidosis, Hungarian type, with mutant transthyretin (TTR Asp18Gly)

PMID 15377697 2004 Familial leptomeningeal amyloidosis with a transthyretin variant Asp18Gly representing repeated subarachnoid haemorrhages with superficial siderosis.

PMID 12779320 2003 D18G transthyretin is monomeric, aggregation prone, and not detectable in plasma and cerebrospinal fluid: a prescription for central nervous system amyloidosis?

PMID 26156087 2015 Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia.

PMID 12771253 2003 Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His.

PMID 16448460 2006 Transthyretin RNA profiling in livers from transplanted patients affected by familial amyloidotic polyneuropathy, and identification of a dual transcription start point.

PMID 19491989 2009 Oculoleptomeningeal amyloidosis in 3 individuals with the transthyretin variant Tyr69His.

PMID 19922332 2009 Report of five rare or previously unknown amyloidogenic transthyretin mutations disclosed in Sweden.

PMID 25044787 2014 Online registry for mutations in hereditary amyloidosis including nomenclature recommendations.

PMID 1301926 1992 Two transthyretin variants (TTR Ala-49 and TTR Gln-89) in two Sicilian kindreds with hereditary amyloidosis.

PMID 27859927 2017 Clinical features of familial amyloid polyneuropathy carrying transthyretin mutations in four Chinese kindreds.

PMID 26115788 2015 Three Turkish families with different transthyretin mutations.

PMID 21692911 2011 Variable presentations of TTR-related familial amyloid polyneuropathy in seventeen patients.

PMID 29941560 2018 Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease.

PMID 22580845 2012 Sporadic transthyretin amyloidosis with a novel TTR gene mutation misdiagnosed as primary amyloidosis.

PMID 29455155 2018 Newly designed 11-gene panel reveals first case of hereditary amyloidosis captured by massive parallel sequencing.

PMID 24061768 2013 Inherited neuropathies: an update.

PMID 25828388 2015 Distinctive Patterns of Transthyretin Amyloid in Salivary Tissue: A Clinicopathologic Study of 92 Patients With Amyloid-containing Minor Salivary Gland Biopsies.

PMID 26208957 2015 Rapid progression of familial amyloidotic polyneuropathy: a multinational natural history study.

PMID 25644864 2015 Asp58Ala is the predominant mutation of the TTR gene in Korean patients with hereditary transthyretin-related amyloidosis.

PMID 23126592 2012 A transthyretin variant, Asp18Asn, associated with amyloid cardiomyopathy: a new African-American variant?

PMID 10611950 1999 ATTR Phe33Val was found in a Chinese FAP patient and ATTR Ala97Ser in a Taiwanese.

PMID 8133316 1994 Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly).

PMID 22412233 2012 Direct tissue evaluation via immunofluorescence: in the diagnosis of hereditary transthyretin cardiac amyloidosis.

PMID 26521788 2015 Hereditary Transthyretin Amyloidosis in Eight Chinese Families.

PMID 14986482 2003 Clinical and pathological studies of cardiac amyloidosis in transthyretin type familial amyloid polyneuropathy.

PMID 20714957 2010 Pathology and functional diagnosis of small-fiber painful neuropathy.

PMID 20937937 2011 Our study included 8 cases of acquired monoclonal immunoglobulin light chain amyloidosis, 11 cases of transthyretin amyloidosis (3 with the Val30Met mutation, 2 with the Val32Ala mutation, 2 with the Thr60Ala mutation, 1 with the Ala109Ser mutation, 1 with the Phe64Leu mutation, 1 with the Ala97Ser mutation, and 1 not sequenced), and 2 cases of gelsolin amyloidosis (1 with the Asp187Asn mutation and 1 not sequenced).

PMID 20697105 2010 This study investigated skin innervation and its clinical significance in genetically defined FAP due to a hot-spot Ala97Ser TTR mutation (Ala97Ser).

PMID 18022643 2008 These five FAP patients shared an identical missense mutation, Ala97Ser, in the TTR gene.

PMID 17698792 2007 Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP).

PMID 16194874 2005 Cardiomyopathy in Swedish patients with the Gly53Glu and His88Arg transthyretin variants.

PMID 16194875 2005 A Swedish family with the rare Phe33Leu transthyretin mutation.

PMID 11940682 2002 It is also noteworthy that serious cardiac amyloidosis is commonly seen in patients with FAP of the non-Val30Met TTR type.

PMID 22620962 2012 Genotype--phenotype correlation in FAP.

PMID 15249622 2004 Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy.

PMID 19709674 2009 Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy.

PMID 18925456 2008 Heterogeneity of penetrance in familial amyloid polyneuropathy, ATTR Val30Met, in the Swedish population.

PMID 25550818 2014 Evidence of the presence of amyloid substance in the blood of familial amyloidotic polyneuropathy patients with ATTR Val30Met mutation.

PMID 11709003 2001 A case of familial amyloid polyneuropathy homozygous for the transthyretin Val30Met gene with motor-dominant sensorimotor polyneuropathy and unusual sural nerve pathological findings.

PMID 23080516 2012 Inability of mutant transthyretin V30M to cross the blood-eye barrier.

PMID 24601850 2014 Gene expression analysis was used to unravel the genetic profiles of Swedish ATTR V30M patients and controls.

PMID 19808383 2009 Heart failure and cardiac involvement as isolated manifestation of familial form of transthyretin amyloidosis resulting from Val30Met mutation with no clinical signs of polyneuropathy.

PMID 14986482 2003 Cardiac amyloidosis occurs in the classical form of FAP with ATTR Val30Met, especially in older patients, and is also a common clinical manifestation in FAP patients with non-Val30Met ATTRs.

PMID 10611950 1999 A matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) mass spectrometry (MS) system was used to detect variant transthyretin (TTR) in immunoprecipitated serum TTR molecules obtained from 6 patients with familial amyloid polyneuropathy (FAP) who were already proven not to have ATTR Val30Met.

PMID 24455802 2014 Unexplained cardiac failure leading to the identification of a Belgian family affected by hereditary amyloidosis.

PMID 6736244 1984 Amyloid fibril protein in familial amyloidotic polyneuropathy, Portuguese type. Definition of molecular abnormality in transthyretin (prealbumin).

PMID 25551524 2015 The amyloidogenic V122I transthyretin variant in elderly black Americans.

PMID 22877808 2012 Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis Cardiac Study (TRACS).

PMID 26123279 2015 Prevalence of the amyloidogenic transthyretin (TTR) V122I allele in 14 333 African-Americans.

PMID 2349941 1990 A homozygous transthyretin variant associated with senile systemic amyloidosis: evidence for a late-onset disease of genetic etiology.

PMID 9017939 1997 Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans.

PMID 18276611 2008 Different disease-causing mutations in transthyretin trigger the same conformational conversion.

PMID 11752443 2001 The V122I cardiomyopathy variant of transthyretin increases the velocity of rate-limiting tetramer dissociation, resulting in accelerated amyloidosis.

PMID 24633258 2014 An Afro-Caribbean patient with a thick heart.

PMID 20435197 2010 Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.

PMID 25819286 2015 Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy.

PMID 25846356 2015 The Val142Ile transthyretin cardiac amyloidosis: more than an Afro-American pathogenic variant.

PMID 24474780 2014 Proteolytic cleavage of Ser52Pro variant transthyretin triggers its amyloid fibrillogenesis.

PMID 22209138 2012 Carpal tunnel syndrome as an initial manifestation in a case of transthyretin-related familial amyloid polyneuropathy with a novel A120T mutation.

rs121918088 in TTR gene and Carpal Tunnel Syndrome PMID 8309582 1994 Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant.

rs1555631390 in TTR gene and Dysautonomia PMID 29941560 2018 Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease.

rs267607159 in TTR gene and Dystransthyretinemic Euthyroidal Hyperthyroxinemia PMID 1979335 1990 A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia.

rs1555631390 in TTR gene and Myofibrillar Myopathy PMID 29941560 2018 Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease.

rs1555631390 in TTR gene and Sensorimotor neuropathy PMID 29941560 2018 Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease.

rs1791227 in TTR gene and Serum total cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.