Protein / target

Thyrotropin receptor

TSHRP16473Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Small-molecule tractable
Druggability
Structure with Ligand
1
Drugs targeting

Protein at a glance

Biological role

Thyroid-stimulating hormone receptor activity

Primary system

Endocrine & metabolic

Strongest disease association

hypothyroidism

Genetic evidence · score 0.97

Therapeutic maturity

Clinically validated target

2 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Structure with Ligand

Clinical development

2 approved

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

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.

G protein-coupled signallingGOKinase signallingUniProt
View supporting evidence

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

Kinase signalling

  • ·Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubM…
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

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.

Thyrotropin
Narrow target profileApprovedAgonist

Thyroid stimulating hormone receptor agonist

Appears in clinical studies involving hypothyroidism, differentiated thyroid carcinoma, differentiated thyroid carcinoma, toxic multinodular goitre

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

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.

hypothyroidism0.97

Genetic · overall 0.78

familial hyperthyroidism due to mutations in TSH receptor0.93

Genetic · overall 0.82

hypothyroidism due to TSH receptor mutations0.92

Genetic · overall 0.83

thyroid gland disorder0.92

Genetic · overall 0.71

familial gestational hyperthyroidism0.82

Genetic · overall 0.72

Highest-confidence therapeutic associations

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

hyperthyroidism0.12

Clinical · overall 0.48

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

myxedema0.61

Genetic

congenital hypothyroidism0.59

Genetic

Graves disease0.51

Genetic

hereditary disease0.50

Genetic

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 gland disorder0.71
myxedema0.61
congenital hypothyroidism0.59
Graves disease0.51
hereditary disease0.50
hyperthyroidism0.48

Open Targets ranks 1,459 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 · 2 total

THYROTROPIN ALFAApproval

thyroid gland carcinoma · thyroid cancer · thyroid tumor

THYROTROPINApproval

hypothyroidism · differentiated thyroid carcinoma · differentiated thyroid carcinoma

Tractability

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

Safety liabilities

regulation of transcription factor activity

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.

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 gland disorderWell 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

16

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 publication2024-11-01
    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 publication2023-10-16
    Thyroid hormone sensitivity and diabetes onset: a longitudinal cross-lagged cohort.

    Frontiers in endocrinology · 2023 · 7 citations · Europe PMC · via Thyrotropin

  12. 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

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.