Protein / target

Thyroid hormone receptor beta

THRBP10828Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
8
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Sequence-specific double-stranded DNA binding

Primary system

Endocrine & metabolic

Strongest disease association

glycogen storage disease due to glycogen branching enzyme deficiency

Genetic evidence · score 0.98

Therapeutic maturity

Clinically validated target

8 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

8 approved · 2 in clinical development

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

Nucleus
Domains and Gene Ontology detail (26)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Cnuclear body
  • Cnucleoplasm
  • Cnucleus
  • CRNA polymerase II transcription regulator complex
  • Fchromatin DNA binding
  • FDNA binding
  • FDNA-binding transcription factor activity
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Fenzyme binding
  • Fnuclear receptor activity
  • FRNA polymerase II cis-regulatory region sequence-specific DNA binding

461 aa · 53 kDa · 2 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.

RXRANCOA2NCOA1NCOR1PIK3R1NCOR2TXNRD2THRANCOA3MAPK3THRB

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

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.

resmetirom
Narrow target profileApprovedAgonist

Thyroid hormone receptor beta-1 agonist

Appears in clinical studies involving metabolic dysfunction-associated steatotic liver disease, cirrhosis of liver, metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis

Direct interaction with this protein · Only this protein recorded as a target

Thyroid hormone receptor agonist

Acts on a complex — shared with THRA · 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.

glycogen storage disease due to glycogen branching enzyme deficiency0.98

Genetic · overall 0.69

thyroid hormone resistance, generalized, autosomal dominant0.94

Genetic · overall 0.72

thyroid hormone resistance, generalized, autosomal recessive0.91

Genetic literature · overall 0.69

generalized resistance to thyroid hormone0.88

Genetic literature · overall 0.77

selective pituitary resistance to thyroid hormone0.88

Genetic literature · overall 0.78

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 0.53

metabolic dysfunction-associated steatotic liver disease0.84

Clinical · overall 0.53

hyperthyroidism0.01

Clinical · overall 0.52

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

thyroid hormone resistance syndrome0.49

Genetic

Show all associations
selective pituitary resistance to thyroid hormone0.78
generalized resistance to thyroid hormone0.77
thyroid hormone resistance, generalized, autosomal dominant0.72
glycogen storage disease due to glycogen branching enzyme deficiency0.69
thyroid hormone resistance, generalized, autosomal recessive0.69
hypothyroidism0.61
metabolic dysfunction-associated steatotic liver disease0.53
differentiated thyroid carcinoma0.53
hyperthyroidism0.52
thyroid hormone resistance syndrome0.49

Open Targets ranks 3,589 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 · 10 total

TIRATRICOLApproval

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

LEVOTHYROXINEApproval

hypothyroidism · hypothyroidism · Shock

DEXTROTHYROXINEApproval

cardiovascular disorder

LIOTHYRONINE SODIUMApproval

hypothyroidism · differentiated thyroid carcinoma · myxedema

LIOTHYRONINEApproval

hypothyroidism · congestive heart failure · bipolar disorder

LEVOTHYROXINE SODIUMApproval

differentiated thyroid carcinoma · hypothyroidism · thyroid cancer

EPROTIROMEPhase 3

cardiovascular disorder · Hypercholesterolemia · Hypercholesterolemia

RESMETIROMApproval

metabolic dysfunction-associated steatotic liver disease · cirrhosis of liver · metabolic dysfunction-associated steatotic liver disease

DEXTROTHYROXINE SODIUMApproval
MB07811Phase 2

familial hyperlipidemia · Hypercholesterolemia · fatty liver disease

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · Small Molecule Binder

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

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.

glycogen storage disease due to glycogen branching enzyme deficiencyWell supported
0.97
agreement 0.851.00
Genetic100%Genetic literaturedup

Open Targets aggregate 0.69 · 1 independent evidence family · 1 not counted as duplicate

thyroid hormone resistance, generalized, autosomal dominantWell supported
0.96
agreement 0.841.00
Genetic75%Animal model25%Literature0%Genetic literaturedup

Open Targets aggregate 0.72 · 3 independent evidence families · 1 not counted as duplicate

selective pituitary resistance to thyroid hormoneWell supported
0.89
agreement 0.771.00
Genetic71%Animal model28%Literature1%Genetic literaturedup

Open Targets aggregate 0.78 · 3 independent evidence families · 1 not counted as duplicate

thyroid hormone resistance, generalized, autosomal recessiveWell supported
0.87
agreement 0.750.99
Genetic77%Animal model23%Literature0%Genetic literaturedup

Open Targets aggregate 0.69 · 3 independent evidence families · 1 not counted as duplicate

generalized resistance to thyroid hormoneWell supported
0.85
agreement 0.730.97
Genetic70%Animal model28%Literature2%Genetic literaturedup

Open Targets aggregate 0.77 · 3 independent evidence families · 1 not counted as duplicate

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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

17

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Label change2026-07-24

    Label change: RESMETIROM (NDA217785)

    fda · regulatory · fda · via resmetirom

  2. Label change2025-12-19

    Label change: RESMETIROM (NDA217785)

    fda · regulatory · fda · via resmetirom

  3. Label change2025-12-19

    Label change: RESMETIROM (NDA217785)

    fda · regulatory · fda · via resmetirom

  4. Label change2025-12-19

    Label change: RESMETIROM (NDA217785)

    fda · regulatory · fda · via resmetirom

  5. Regulatory approval2025-08-18

    Approval: Rezdiffra (EMA)

    ema · regulatory · ema · via resmetirom

  6. New publication2024-12-20
    Thyroid hormone and the Liver.

    Hepatology communications · 2025 · 13 citations · Europe PMC · via resmetirom

  7. New publication2024-12-10
    Hepatic thyroid hormone receptor-β signalling: Mechanisms and recent advancements in the treatment of metabolic dysfunction-associated steatohepatitis.

    Diabetes, obesity & metabolism · 2025 · 14 citations · Europe PMC · via resmetirom

  8. New publication2024-10-19
    Thyroid hormone receptor-β analogues for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).

    Journal of hepatology · 2025 · 38 citations · Europe PMC · via resmetirom

  9. 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

  10. 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

  11. New publication2024-04-05
    The first MASH drug therapy on the horizon: Current perspectives of resmetirom.

    Liver international : official journal of the International Association for the Study of the Liver · 2024 · 117 citations · Europe PMC · via resmetirom

  12. New publication2024-03-19
    Resmetirom, the first approved drug for the management of metabolic dysfunction-associated steatohepatitis: Trials, opportunities, and challenges.

    Metabolism: clinical and experimental · 2024 · 114 citations · Europe PMC · via resmetirom

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.