PTH1R Gene (Parathyroid Hormone 1 Receptor)
Genetic, structural, and clinical insights into the PTH1R gene, its role in skeletal development, calcium homeostasis, and associated disorders.
Gene Information Card
| Symbol | PTH1R |
|---|---|
| Full Name | Parathyroid Hormone 1 Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 5745 ncbi.nlm.nih.gov/gene/5745 |
| Ensembl ID | ENSG00000101276 |
| UniProt ID | Q03431 |
| OMIM ID | 168468 |
| HGNC ID | 9608 |
| Aliases | PTHR1, PTHR, PFEIFFER, MGC138426, MGC142160 |
Description
The PTH1R gene encodes the parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R), a G-protein coupled receptor (GPCR) that mediates the actions of parathyroid hormone (PTH) and PTH-related protein (PTHrP). This receptor is critical for calcium homeostasis, bone remodeling, and endochondral bone development. Mutations in PTH1R are associated with several skeletal dysplasias and hyperparathyroidism syndromes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Jansen metaphyseal chondrodysplasia | Activating mutations in PTH1R lead to constitutive activation of the receptor, causing abnormal chondrocyte differentiation and growth plate disruption. | OMIM 156400; ClinVar |
| Blomstrand chondrodysplasia | Inactivating mutations in PTH1R impair PTHrP signaling, leading to advanced skeletal maturation and lethal chondrodysplasia. | OMIM 215045; ClinVar |
| Eiken syndrome | Homozygous loss-of-function mutations in PTH1R cause delayed bone maturation and epiphyseal dysplasia. | OMIM 600002; ClinVar |
| Primary hyperparathyroidism | Somatic mutations in PTH1R may contribute to parathyroid adenoma formation, though the mechanism is not fully defined. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 12.3 | Medium |
| Kidney | 8.7 | Low |
| Cartilage | 15.2 | Medium |
| Lung | 5.4 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Saos-2 (osteosarcoma) | 18.5 | High expression; used as osteoblast model |
| U2OS (osteosarcoma) | 12.0 | Moderate expression |
| HEK293 (embryonic kidney) | 3.2 | Low endogenous; often used for transfection |
| HepG2 (liver) | 0.8 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1124C>T (p.Thr375Met) | Missense | Rare (germline) | Activating; associated with Jansen metaphyseal chondrodysplasia |
| c.1130G>A (p.Arg377His) | Missense | Rare (germline) | Activating; Jansen metaphyseal chondrodysplasia |
| c.1056C>G (p.Tyr352*) | Nonsense | Rare (germline) | Loss-of-function; Blomstrand chondrodysplasia |
| c.544C>T (p.Arg182Cys) | Missense | Rare (germline) | Loss-of-function; Eiken syndrome |
Mutation functional classification
Loss of Function (LOF)
Inactivating mutations (e.g., nonsense, frameshift, or missense) impair receptor signaling, leading to Blomstrand chondrodysplasia or Eiken syndrome.
Gain of Function (GOF)
Activating mutations (e.g., missense in transmembrane domains) cause constitutive receptor activity, resulting in Jansen metaphyseal chondrodysplasia.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming non-functional dimers, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • G-protein coupled receptor activity | • parathyroid hormone receptor activity |
| • peptide hormone binding | • plasma membrane |
| • signal transduction | • adenylate cyclase-activating G-protein coupled receptor signaling pathway |
| • bone development | • calcium ion homeostasis |
Pathways
• GPCR downstream signaling
• PTH/PTHrP signaling in bone development
• cAMP/PKA signaling pathway
• Regulation of osteoblast differentiation
Protein Summary
The PTH1R protein is a 593-amino acid seven-transmembrane GPCR. It binds PTH and PTHrP with equal affinity, activating Gs and Gq proteins, leading to cAMP accumulation and intracellular calcium mobilization. The receptor is essential for skeletal development, particularly in growth plate chondrocyte proliferation and differentiation. Structural studies reveal a large extracellular domain for ligand binding and intracellular loops for G-protein coupling. Post-translational modifications include glycosylation and phosphorylation, which modulate receptor activity and desensitization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTH1R Knockout HEK293 Cell Line | EDJ-KQ3468 | Human | 5745 | Details Get a Quote |
| PTH1R Knockout HeLa Cell Line | EDJ-KQ54263 | Human | 5745 | Details Get a Quote |
| PTH1R Knockout A-549 Cell Line | EDJ-KQ62755 | Human | 5745 | Details Get a Quote |
| PTH1R Knockout HCT 116 Cell Line | EDJ-KQ71224 | Human | 5745 | Details Get a Quote |
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