Protein / target

Parathyroid hormone/parathyroid hormone-related peptide receptor

PTH1RQ03431Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
16
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

G protein-coupled peptide receptor activity

Primary system

Endocrine & metabolic

Strongest disease association

metaphyseal chondrodysplasia, Jansen type

Genetic evidence · score 0.85

Therapeutic maturity

Clinically validated target

5 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Structure with Ligand

Clinical development

5 approved · 1 in clinical development

16 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

G protein-coupled receptor for parathyroid hormone (PTH) and for parathyroid hormone-related peptide (PTHLH) (PubMed:10913300, PubMed:18375760, PubMed:19674967, PubMed:27160269, PubMed:30975883, PubMed:35932760, PubMed:8397094). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (cAMP) (PubMed:30975883, PubMed:35932760). PTH1R is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:20172855, PubMed:30975883, PubMed:35932760). PTHLH dissociates from PTH1R more rapidly than PTH; as consequence, the cAMP response induced by PTHLH decays faster than the response induced by PTH (PubMed:35932760)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (20)

Gene Ontology

  • Capical plasma membrane
  • Cbasolateral plasma membrane
  • Ccytoplasm
  • Cnucleus
  • Cplasma membrane
  • Creceptor complex
  • FG protein-coupled peptide receptor activity
  • FG protein-coupled receptor activity
  • Fparathyroid hormone receptor activity
  • Fpeptide hormone binding
  • Fprotein homodimerization activity
  • Padenylate cyclase-activating G protein-coupled receptor signaling pathway

593 aa · 66 kDa

Biological roles

Reactome v97

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

G protein-coupled signallingUniProt · GO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled receptor for parathyroid hormone (PTH) and for parathyroid hormone-rel…
  • ·G protein-coupled peptide receptor activity
  • ·G protein-coupled receptor activity
  • ·adenylate cyclase-activating 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.

PTHLHPTHGNASLRP6ARRB1ARRB2PTH2GNAQGNAI1GNA11PTH1R

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.

Parathyroid Hormone
Narrow target profileApprovedAgonist

Parathyroid hormone receptor agonist

Appears in clinical studies involving Hypocalcemia, hypoparathyroidism, postmenopausal osteoporosis, osteoporosis

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.

metaphyseal chondrodysplasia, Jansen type0.85

Genetic · overall 0.77

Abnormality of the skeletal system0.85

Genetic · overall 0.51

primary failure of tooth eruption0.83

Genetic · overall 0.74

Blomstrand lethal chondrodysplasia0.82

Genetic literature · overall 0.67

chondrodysplasia Blomstrand type0.82

Genetic · overall 0.75

Highest-confidence therapeutic associations

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

osteoporosis0.99

Clinical · overall 0.61

hypoparathyroidism0.95

Clinical · overall 0.58

postmenopausal osteoporosis0.93

Clinical · overall 0.56

bone fracture0.88

Clinical · overall 0.54

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Eiken syndrome0.71

Genetic literature

Show all associations
metaphyseal chondrodysplasia, Jansen type0.77
chondrodysplasia Blomstrand type0.75
primary failure of tooth eruption0.74
Eiken syndrome0.71
Blomstrand lethal chondrodysplasia0.67
osteoporosis0.61
hypoparathyroidism0.58
postmenopausal osteoporosis0.56
bone fracture0.54
Abnormality of the skeletal system0.51

Open Targets ranks 1,304 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 · 6 total

PARATHYROID HORMONEApproval

Hypocalcemia · hypoparathyroidism · postmenopausal osteoporosis

PALOPEGTERIPARATIDEApproval

hypoparathyroidism

TERIPARATIDE ACETATEApproval

bone fracture · osteoporosis

TERIPARATIDEApproval

osteoporosis · bone fracture · osteogenesis imperfecta

OSTABOLIN-CPhase 2

osteoporosis

ABALOPARATIDEApproval

osteoporosis · postmenopausal osteoporosis · lumbar disk degenerative disorder

Tractability

SM · Structure with LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Small Molecule BinderOC · Approved Drug

Clinical trials

16

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 (10)

COMPLETED · via Parathyroid Hormone · NCT00000427

COMPLETED · via Parathyroid Hormone · NCT00853723

COMPLETED · via Parathyroid Hormone · NCT00221299

COMPLETED · via Parathyroid Hormone · NCT00005006

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.

metaphyseal chondrodysplasia, Jansen typeWell supported
0.87
agreement 0.750.99
Genetic87%Animal model12%Literature2%Genetic literaturedup

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

primary failure of tooth eruptionWell supported
0.86
agreement 0.740.98
Genetic81%Animal model10%Literature8%Genetic literaturedup

Open Targets aggregate 0.74 · 3 independent evidence families · 1 not counted as duplicate

Abnormality of the skeletal systemWell supported
0.85
agreement 0.730.97
Genetic100%

Open Targets aggregate 0.51 · 1 independent evidence family

chondrodysplasia Blomstrand typeWell supported
0.84
agreement 0.720.96
Genetic86%Animal model13%Literature1%Genetic literaturedup

Open Targets aggregate 0.75 · 3 independent evidence families · 1 not counted as duplicate

Eiken syndromeWell supported
0.82
agreement 0.700.94
Genetic80%Animal model16%Literature4%Genetic literaturedup

Open Targets aggregate 0.71 · 3 independent evidence families · 1 not counted as duplicate

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

8

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. Withdrawn from market2026-07-01

    Market withdrawal: Natpar (EMA)

    ema · market · ema · via Parathyroid Hormone

  2. New publication2025-10-01
    Revised European Society of Endocrinology Clinical Practice Guideline: Treatment of Chronic Hypoparathyroidism in Adults.

    European journal of endocrinology · 2025 · 8 citations · Europe PMC · via Parathyroid Hormone

  3. New publication2023-08-01
    Role of Parathyroid Hormone and Parathyroid Hormone-Related Protein in Protein-Energy Malnutrition.

    Frontiers in bioscience (Landmark edition) · 2023 · 5 citations · Europe PMC · via Parathyroid Hormone

  4. Regulatory approval2017-04-24

    Approval: Natpar (EMA)

    ema · regulatory · ema · via Parathyroid Hormone

  5. New publication2013-04-16
    Postmenopausal women treated with combination parathyroid hormone (1-84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS).

    Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2013 · 20 citations · Europe PMC · via Parathyroid Hormone

  6. New publication2012-07-12
    Six months of parathyroid Hormone (1-84) administered concurrently versus sequentially with monthly ibandronate over two years: the PTH and ibandronate combination study (PICS) randomized trial.

    The Journal of clinical endocrinology and metabolism · 2012 · 35 citations · Europe PMC · via Parathyroid Hormone

  7. New publication2007-11-28
    Chronic kidney disease mineral and bone disorder in children.

    Pediatric nephrology (Berlin, Germany) · 2008 · 47 citations · Europe PMC · via Parathyroid Hormone

  8. New publication2004-02-01
    Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism.

    The Journal of clinical investigation · 2004 · 1,111 citations · Europe PMC · via Parathyroid Hormone

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.