TTR
Chr 18ADtransthyretin
Also known as: AMYLD1, ATTR, CTS, CTS1, HEL111, HsT2651, PALB, TBPA
Transthyretin is a tetrameric carrier protein that transports thyroid hormones in plasma and cerebrospinal fluid and also transports retinol (vitamin A) by associating with retinol-binding protein. Mutations cause autosomal dominant hereditary transthyretin amyloidosis, which predominantly affects peripheral nerves and heart, as well as dystransthyretinemic hyperthyroxinemia and familial carpal tunnel syndrome. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.763), and amyloidosis typically presents in adulthood with progressive polyneuropathy or cardiomyopathy.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TTR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.
RECRUITINGEarly Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories
RECRUITINGSEarchiNg biomarkErs Cerebral Amyloid Angiopathy (SENECA)
RECRUITINGA Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients
RECRUITINGEFICAC-TTR Trial: Exercise and Nutritional Supplementation in Transthyretin Cardiac Amyloidosis
NOT YET RECRUITINGTrial of Perioperative Endocrine Therapy - Individualising Care
ACTIVE NOT RECRUITINGA Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
RECRUITINGA Study of XZP-5955 Tablets in Patients With NTRK or ROS1 Fusion Positive Locally Advanced or Metastatic Solid Tumors
RECRUITINGA Dose-escalating Pilot Study of Orelabrutinib for Newly-diagnosed PCNSL
ACTIVE NOT RECRUITINGExploratory Clinical Study of TCR-T for MAGE-A4-positive Mesenchymal Malignancies
RECRUITINGA Clinical Study Exploring the Safety, Efficacy and Cell Metabolic Kinetics of Universal Car-t Cell Injection in CD19 and / or CD20 Positive Relapsed / Refractory B-cell Acute Lymphoblastic Leukemia in Adolescents, Children and Adults
RECRUITINGStudy to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools