TTR

Chr 18AD

transthyretin

Also known as: AMYLD1, ATTR, CTS, CTS1, HEL111, HsT2651, PALB, TBPA

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. [provided by RefSeq, Aug 2017]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Dystransthyretinemic hyperthyroxinemia]MIM #145680
AD
Amyloidosis, hereditary systemic 1MIM #105210
AD
Carpal tunnel syndrome, familialMIM #115430
AD
UniProtHyperthyroxinemia, dystransthyretinemic

Clinical highlights

Gene-disease validity (ClinGen)
obsolete hereditary ATTR amyloidosis · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
908
Pubs (1 yr)
P/LP submissions
P/LP missense
0.76
LOEUF
GOF
Mechanism· G2P
📖
GeneReview available — TTR
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.76LOEUF
pLI 0.516
Z-score 1.94
OE 0.16 (0.060.76)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?
1.01Z-score
OE missense 0.69 (0.550.86)
57 obs / 83.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.16 (0.060.76)
00.351.4
Missense OE?0.69 (0.550.86)
00.61.4
Synonymous OE?0.90
01.21.6
LoF obs/exp: 1 / 6.2Missense obs/exp: 57 / 83.0Syn Z: 0.43

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Multiple Myeloma

A Clinical Study of TQB2029 for Injection in Subjects With Multiple Myeloma

RECRUITING
NCT06700395Phase PHASE1Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.Started 2024-11-28
TQB2029 injection
Lumbar Spinal StenosisCardiac AmyloidosisATTR Amyloidosis Wild Type

Analysis of Lumbar Spine Stenosis Specimens for Identification of Transthyretin Cardiac Amyloidosis

RECRUITING
NCT06034405Columbia UniversityStarted 2023-09-19
Tc99-PYP or Tc99-HDMP Scan
Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen

Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen

RECRUITING
NCT06127407Phase PHASE3Servier Bio-Innovation LLCStarted 2024-07-09
Ivosidenib 500mgPlacebo
PTCLT Cell Lymphoma

A Multi-center, Prospective, Registry Study to Analyze the Clinical Characteristics and Prognosis of Different Molecular Subtypes of Peripheral T-cell Lymphoma.

NOT YET RECRUITING
NCT07657572Ruijin HospitalStarted 2026-06
Stomach NeoplasmsNeoadjuvant Therapy

Family-Supervised Prehabilitation to Reduce Postoperative Complications After Neoadjuvant Chemotherapy in Gastric Cancer

NOT YET RECRUITING
NCT07183358Phase NAThe Affiliated Hospital of Qingdao UniversityStarted 2025-09-20
Family-supervised Multimodal PrehabilitationStandard Care
Relapsed/Refractory B-cell Malignancies

IASO208 Injection in the Treatment of Relapsed/Refractory B-cell Malignancies

RECRUITING
NCT07309900Phase PHASE1Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyStarted 2025-11-21
IASO208 injection
Acute Myeloid LeukemiaAcute Lymphoblastic LeukemiaMixed Lineage Acute Leukemia

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

RECRUITING
NCT04065399Phase PHASE1, PHASE2Syndax PharmaceuticalsStarted 2019-11-05
revumenibcobicistat
Non-small Cell Lung Cancer

A Trial to Learn How the Combination of Fianlimab With Cemiplimab and Chemotherapy Works Compared With Cemiplimab and Chemotherapy for Treating Adult Patients With Advanced Non-small Cell Lung Cancer

ACTIVE NOT RECRUITING
NCT05800015Phase PHASE2, PHASE3Regeneron PharmaceuticalsStarted 2023-08-08
fianlimabcemiplimabPemetrexed
Duchenne Muscular Dystrophy

A Study of SGT-003 Gene Therapy in Duchenne Muscular Dystrophy (INSPIRE DUCHENNE)

RECRUITING
NCT06138639Phase PHASE1, PHASE2Solid Biosciences Inc.Started 2024-05-06
SGT-003
Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Single-arm, Multi-center Study Evaluating the Acceptance and Feasibility of a Digital Remote Monitoring Tool Configured for Patients With ATTR-CM: ACO-Monitor

NOT YET RECRUITING
NCT07557147BayerStarted 2026-08-31
Luscii
Non Small Cell Lung Cancer

A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene

ACTIVE NOT RECRUITING
NCT04395677Phase PHASE2Nuvation Bio Inc.Started 2020-07-07
AB-106
Non-Small Cell Lung Cancer

IMP3-saRNA Vaccine in Advanced NSCLC

RECRUITING
NCT07561723Phase PHASE1West China HospitalStarted 2026-04-30
IMP3-saRNA (YMN-136) Vaccine