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Protein / target

Thyrotropin receptor

Encoded byTSHRP16473Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
Small-molecule tractable
Druggability
Structure with Ligand
1
Drugs targeting

Protein at a glance

Biological role

Thyroid-stimulating hormone receptor

Strongest disease association

Hypothyroidism

Via encoding gene TSHR · Genetic evidence · score 0.97

Therapeutic position

Established drug target

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

Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin.

View complete UniProt function annotation

Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin (PubMed:12045258). TSHR is coupled to G(s) proteins and mediates the activation of adenylate cyclase (PubMed:11847099, PubMed:35940205, PubMed:35940204). This leads to the generation of cyclic adenosine monophosphate (cAMP), which in turn activates protein kinase A (PKA). PKA subsequently phosphorylates downstream targets involved in thyroid hormone biosynthesis and secretion, including thyroid peroxidase (TPO) and the sodium/iodide symporter (NIS) (PubMed:27638195). Additionally, plays a central role in controlling thyroid cell metabolism (By similarity)

Subcellular location

Cell membraneBasolateral cell membrane
Domains and Gene Ontology detail (20)

Gene Ontology

  • Cbasolateral plasma membrane
  • Ccell surface
  • Cplasma membrane
  • Creceptor complex
  • FG protein-coupled peptide receptor activity
  • FG protein-coupled receptor activity
  • Fprotein-containing complex binding
  • Fsignaling receptor activity
  • Fthyroid-stimulating hormone receptor activity
  • Padenylate cyclase-activating G protein-coupled receptor signaling pathway
  • Pcell surface receptor signaling pathway
  • Pcell-cell signaling

764 aa · 87 kDa · 3 isoforms

Biological roles

Reactome v97

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

Cell proliferation & survivalGOG protein-coupled signallingGO
View supporting evidence

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

G protein-coupled signalling

  • ·G protein-coupled peptide receptor activity
  • ·G protein-coupled receptor activity
  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
  • ·G protein-coupled receptor signaling 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.

TSHBGNASTGTPOCGAGNAQNKX2-1IGF1RFSHBSLC5A5TSHR

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

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.

Thyrotropin
Narrow target profileApprovedAgonist

Thyroid stimulating hormone receptor agonist

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

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 TSHR

Gene-level evidence surfaced through the gene TSHRthat 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.

Hypothyroidism
0.99Well supported

Genetic evidence dominant · Open Targets 0.78

familial hyperthyroidism due to mutations in TSH receptor
0.94Well supported

Genetic evidence dominant · Open Targets 0.82

hypothyroidism due to TSH receptor mutations
0.94Well supported

Genetic evidence dominant · Open Targets 0.83

Thyroid Diseases
0.93Well supported

Genetic evidence dominant · Open Targets 0.71

Familial gestational hyperthyroidism
0.86Well supported

Genetic evidence dominant · Open Targets 0.72

View evidence synthesis (5)
HypothyroidismWell supported
0.99
agreement 0.881.00
Genetic65%Clinical31%Literature4%

Open Targets aggregate 0.78 · 3 independent evidence families

familial hyperthyroidism due to mutations in TSH receptorWell supported
0.94
agreement 0.821.00
Genetic81%Animal model17%Literature2%Genetic literaturedup

Open Targets aggregate 0.82 · 3 independent evidence families · 1 not counted as duplicate

hypothyroidism due to TSH receptor mutationsWell supported
0.94
agreement 0.821.00
Genetic81%Animal model19%Literature0%Genetic literaturedup

Open Targets aggregate 0.83 · 3 independent evidence families · 1 not counted as duplicate

Thyroid DiseasesWell supported
0.93
agreement 0.791.00
Genetic95%Literature5%

Open Targets aggregate 0.71 · 2 independent evidence families

Familial gestational hyperthyroidismWell supported
0.86
agreement 0.730.98
Genetic78%Animal model22%Genetic literaturedup

Open Targets aggregate 0.72 · 2 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 per-type scores above show the calculation.

Show all associations
hypothyroidism due to TSH receptor mutations0.83
familial hyperthyroidism due to mutations in TSH receptor0.82
Hypothyroidism0.78
Familial gestational hyperthyroidism0.72
Thyroid Diseases0.71
Myxedema0.61
Congenital Hypothyroidism0.59
Graves' Disease0.51
Genetic Diseases, Inborn0.50
Hyperthyroidism0.48

Drug development

2 compounds recorded · 2 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph: these count different sets and are not a subset relation.

View all recorded compounds (2)
THYROTROPIN ALFAApproval
THYROTROPINApproval

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 moleculesEmerging

Feasibility evidence (structure with ligand and druggable family) — no clinical-stage drug of this modality recorded.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (8)
SM · Structure with LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation 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.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets 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. New publication2024-11-01
    Central and Peripheral Sensitivity to Thyroid Hormones Correlate to Metabolically Obesity Phenotypes in Chinese Euthyroid Adults: A Cross-Sectional Study.

    Diabetes/metabolism research and reviews · 2024 · 2 citations · Europe PMC · via Thyrotropin

  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 Thyrotropin

  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 Thyrotropin

  4. New publication2024-08-08
    Associations between sensitivity to thyroid hormones and insulin resistance in euthyroid adults with obesity.

    Frontiers in endocrinology · 2024 · 11 citations · Europe PMC · via Thyrotropin

  5. New publication2024-06-13
    Implications of GLP-1 Receptor Agonist on Thyroid Function: A Literature Review of Its Effects on Thyroid Volume, Risk of Cancer, Functionality and TSH Levels.

    Biomolecules · 2024 · 17 citations · Europe PMC · via Thyrotropin

  6. 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 Thyrotropin

  7. New publication2023-12-27
    Subclinical Hypothyroidism in Patients with Obesity and Metabolic Syndrome: A Narrative Review.

    Nutrients · 2023 · 43 citations · Europe PMC · via Thyrotropin

  8. New publication2023-12-23
    Predictors of controlled attenuation parameter in metabolic dysfunction.

    United European gastroenterology journal · 2024 · 7 citations · Europe PMC · via Thyrotropin

  9. New publication2023-12-21
    Effects of vitamin D supplementation on metabolic parameters, serum irisin and obesity values in women with subclinical hypothyroidism: a double-blind randomized controlled trial.

    Frontiers in endocrinology · 2023 · 10 citations · Europe PMC · via Thyrotropin

  10. New publication2023-10-17
    Environmental Endocrinology: Parabens Hazardous Effects on Hypothalamic-Pituitary-Thyroid Axis.

    International journal of molecular sciences · 2023 · 21 citations · Europe PMC · via Thyrotropin

  11. 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 Thyrotropin

  12. New publication2023-07-03
    Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone.

    Redox biology · 2023 · 21 citations · Europe PMC · via Thyrotropin

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.