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Protein / target

Thyroid hormone receptor alpha

Encoded byTHRAP10827Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
Open Targets target-level
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

General transcription initiation factor binding

Strongest disease association

Peripheral resistance to thyroid hormones

Via encoding gene THRA · Genetic literature evidence · score 0.93

Therapeutic position

Established drug target

Small molecules

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 overview

Nuclear hormone receptor that can act as a repressor or activator of transcription.

View complete UniProt function annotation

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.

Nuclear receptor signallingGO · ReactomeTranscriptional regulationUniProt · GO · Reactome
View supporting evidence

Nuclear receptor signalling

  • ·nuclear receptor activity
  • ·Nuclear Receptor transcription pathway

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
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

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); 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

tiratricol
ApprovedAgonist

Thyroid hormone receptor agonist

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene THRA

Gene-level evidence surfaced through the gene THRAthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Peripheral resistance to thyroid hormones
0.89Well supported

Genetic evidence dominant · Open Targets 0.70

hypothyroidism due to TSH receptor mutations
0.80Well supported

Genetic literature evidence dominant · Open Targets 0.58

Genetic Diseases, Inborn
0.79Well supported

Genetic evidence dominant · Open Targets 0.48

Hypothyroidism
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Thyroid Hormone Resistance Syndrome
0.61Moderately supported

Genetic literature evidence dominant · Open Targets 0.39

View evidence synthesis (5)
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

Genetic Diseases, InbornWell 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

Thyroid Hormone Resistance SyndromeModerately supported
0.61
agreement 0.480.74
Genetic literature66%Animal model32%Literature2%

Open Targets aggregate 0.39 · 3 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Peripheral resistance to thyroid hormones0.70
Hypothyroidism0.61
hypothyroidism due to TSH receptor mutations0.58
Genetic Diseases, Inborn0.48
Neurodegenerative Diseases0.45
Thyroid Neoplasms0.40
Thyrotoxicosis0.40
Thyroid Hormone Resistance Syndrome0.39

Drug development

7 compounds recorded · 7 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph: these count different sets and are not a subset relation.

View all recorded compounds (7)
DEXTROTHYROXINEApproval
TIRATRICOLApproval
LEVOTHYROXINEApproval
DEXTROTHYROXINE SODIUMApproval
LIOTHYRONINE SODIUMApproval
LEVOTHYROXINE SODIUMApproval
LIOTHYRONINEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

receptor bindingToxCastregulation of transcription factor activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

COMPLETED · via Triiodothyronine · NCT00021528

COMPLETED · via Triiodothyronine · NCT00208702

COMPLETED · via Triiodothyronine · NCT02521168

COMPLETED · via Triiodothyronine · NCT04782856

COMPLETED · via Triiodothyronine · NCT04111536

COMPLETED · via Triiodothyronine · NCT04112316

COMPLETED · via Triiodothyronine · NCT03098433

ClinicalTrials.gov via the drug-target graph.

What's happening now

7

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2025-02-12

    Approval: Emcitate (EMA)

    ema · regulatory · ema · via tiratricol

  2. 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

  3. 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

  4. 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

  5. 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

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

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

  7. 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.

Related family literature

7

Papers about “Receptors, Thyroid Hormone” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

Thyroid hormone and the Liver.

Soares De Oliveira L · Hepatology communications · 2025

via Receptors, Thyroid Hormone

The ecological function of thyroid hormones.

Zwahlen J · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024

via Receptors, Thyroid Hormone

Thyroid Hormone Receptors as Tumor Suppressors in Cancer.

Zhu X · Endocrinology · 2024

via Receptors, Thyroid Hormone

Local Thyroid Hormone Action in Brain Development.

Alcaide Martin A · International journal of molecular sciences · 2023

via Receptors, Thyroid Hormone

Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity.

Pillon NJ · Nature communications · 2020

via Receptors, Thyroid Hormone

Molecular aspects of thyroid hormone actions.

Cheng SY · Endocrine reviews · 2010

via Receptors, Thyroid Hormone

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.