Protein / target

Thyroid hormone receptor alpha

THRAP10827Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

General transcription initiation factor binding

Primary system

Endocrine & metabolic

Strongest disease association

peripheral resistance to thyroid hormones

Genetic literature evidence · score 0.93

Therapeutic maturity

Clinically validated target

7 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

7 approved

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine

Subcellular location

NucleusCytoplasm
Domains and Gene Ontology detail (32)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Ccytosol
  • Cnucleoplasm
  • Cnucleus
  • CRNA polymerase II transcription regulator complex
  • Fchromatin DNA binding
  • FDNA-binding transcription factor activity
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Fgeneral transcription initiation factor binding
  • Fnuclear receptor activity
  • Fprotein domain specific binding
  • Fprotein-containing complex binding

490 aa · 55 kDa · 4 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Transcriptional regulationUniProt · GO · ReactomeNuclear receptor signallingGO · Reactome
View supporting evidence

Transcriptional regulation

  • ·Nuclear hormone receptor that can act as a repressor or activator of transcription. High…
  • ·RNA polymerase II transcription regulator complex
  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific

Nuclear receptor signalling

  • ·DNA-binding transcription factor activity
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·nuclear receptor activity
  • ·Nuclear Receptor transcription pathway
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

NCOR1MED1NCOA1RXRAPIK3R1THRBACTBPIK3R2NCOR2PIK3R3THRA

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Thyroid hormone receptor agonist

Acts on a complex — shared with THRB · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

peripheral resistance to thyroid hormones0.93

Genetic literature · overall 0.70

hypothyroidism due to TSH receptor mutations0.93

Genetic literature · overall 0.58

hereditary disease0.79

Genetic · overall 0.48

generalized resistance to thyroid hormone0.61

Genetic literature · overall 0.39

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

hypothyroidism1.00

Clinical · overall 0.61

differentiated thyroid carcinoma0.85

Clinical · overall 0.52

myxedema0.76

Clinical · overall 0.46

thyrotoxicosis0.65

Clinical · overall 0.40

thyroid cancer0.65

Clinical · overall 0.40

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

neurodegenerative disease0.45

Pathway

Show all associations
peripheral resistance to thyroid hormones0.70
hypothyroidism0.61
hypothyroidism due to TSH receptor mutations0.58
differentiated thyroid carcinoma0.52
hereditary disease0.48
myxedema0.46
neurodegenerative disease0.45
thyroid cancer0.40
thyrotoxicosis0.40
generalized resistance to thyroid hormone0.39

Open Targets ranks 1,836 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 7 total

DEXTROTHYROXINEApproval

cardiovascular disorder

TIRATRICOLApproval

thyrotoxicosis · Allan-Herndon-Dudley syndrome · Allan-Herndon-Dudley syndrome

LEVOTHYROXINEApproval

hypothyroidism · hypothyroidism · Shock

DEXTROTHYROXINE SODIUMApproval
LIOTHYRONINE SODIUMApproval

hypothyroidism · differentiated thyroid carcinoma · myxedema

LEVOTHYROXINE SODIUMApproval

differentiated thyroid carcinoma · hypothyroidism · thyroid cancer

LIOTHYRONINEApproval

hypothyroidism · congestive heart failure · bipolar disorder

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Safety liabilities

receptor bindingregulation of transcription factor activity

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

COMPLETED · via Triiodothyronine · NCT04112316

COMPLETED · via Triiodothyronine · NCT04782856

COMPLETED · via Triiodothyronine · NCT04111536

COMPLETED · via Triiodothyronine · NCT02521168

COMPLETED · via Triiodothyronine · NCT00208702

COMPLETED · via Triiodothyronine · NCT00903877

COMPLETED · via Triiodothyronine · NCT03098433

COMPLETED · via Triiodothyronine · NCT00004062

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

peripheral resistance to thyroid hormonesWell supported
0.89
agreement 0.771.00
Genetic83%Animal model17%Literature0%Genetic literaturedup

Open Targets aggregate 0.70 · 3 independent evidence families · 1 not counted as duplicate

hypothyroidism due to TSH receptor mutationsWell supported
0.80
agreement 0.670.92
Genetic literature78%Animal model22%Literature0%

Open Targets aggregate 0.58 · 3 independent evidence families

hereditary diseaseWell supported
0.79
agreement 0.650.93
Genetic99%Literature1%

Open Targets aggregate 0.48 · 2 independent evidence families

hypothyroidismWell supported
0.76
agreement 0.600.91
Clinical96%Literature5%

Open Targets aggregate 0.61 · 2 independent evidence families

differentiated thyroid carcinomaModerately supported
0.64
agreement 0.480.81
Clinical100%

Open Targets aggregate 0.52 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

6

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2024-09-18
    Prevalence of subclinical hypothyroidism and longitudinal thyroid-stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: An observational study.

    Hepatology (Baltimore, Md.) · 2025 · 10 citations · Europe PMC · via Triiodothyronine

  2. New publication2024-09-01
    Thyroid Hormone Homeostasis in Levothyroxine-treated Patients: Findings From ELSA-Brasil.

    The Journal of clinical endocrinology and metabolism · 2024 · 13 citations · Europe PMC · via Triiodothyronine

  3. New publication2024-01-30
    Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

    Nature communications · 2024 · 62 citations · Europe PMC · via Triiodothyronine

  4. New publication2023-09-01
    Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status.

    Thyroid : official journal of the American Thyroid Association · 2023 · 43 citations · Europe PMC · via Triiodothyronine

  5. New publication2020-06-12
    Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

    Nutrients · 2020 · 214 citations · Europe PMC · via Triiodothyronine

  6. New publication2010-01-05
    Molecular aspects of thyroid hormone actions.

    Endocrine reviews · 2010 · 910 citations · Europe PMC · via Triiodothyronine

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.