PTHLH (Parathyroid Hormone Like Hormone)
Key regulator of endochondral bone development and calcium homeostasis; implicated in humoral hypercalcemia of malignancy and breast cancer bone metastasis.
Gene Information Card
| Symbol | PTHLH |
|---|---|
| Full Name | Parathyroid Hormone Like Hormone |
| Gene Type | protein-coding |
| Chromosomal Location | 12p11.22 |
| NCBI Gene ID | 5744 ncbi.nlm.nih.gov/gene/5744 |
| Ensembl ID | ENSG00000187498 |
| UniProt ID | P12272 |
| OMIM ID | 168470 |
| HGNC ID | 9607 |
| Aliases | PTHrP, PLP, HHM, PTHR, PTHRP |
Description
PTHLH (parathyroid hormone like hormone) encodes parathyroid hormone-related protein (PTHrP), a secreted protein that binds to the parathyroid hormone 1 receptor (PTH1R). PTHrP is essential for endochondral bone development, regulating chondrocyte proliferation and differentiation. It also mediates calcium transport across the placenta and mammary gland. Overexpression of PTHLH is a major cause of humoral hypercalcemia of malignancy (HHM) and promotes osteolytic bone metastasis in breast and prostate cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Humoral Hypercalcemia of Malignancy (HHM) | PTHLH overexpression by tumor cells leads to systemic PTHrP secretion, which binds PTH1R in bone and kidney, increasing bone resorption and renal calcium reabsorption, causing hypercalcemia. | ClinVar, COSMIC, NCBI Gene |
| Breast Cancer Bone Metastasis | PTHrP secreted by breast cancer cells activates osteoclasts via RANKL upregulation in osteoblasts, leading to osteolytic lesions. | NCBI Gene, COSMIC |
| Chondrodysplasia (Metaphyseal Chondrodysplasia, Jansen type) | Activating mutations in PTH1R (receptor) mimic PTHrP signaling; PTHLH loss-of-function mutations are associated with skeletal dysplasia. | OMIM #168470 |
| Hyperparathyroidism (secondary) | Elevated PTHrP levels can mimic primary hyperparathyroidism in malignancy. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast (mammary gland) | 12.5 | Medium |
| Placenta | 8.2 | Low |
| Skin | 6.1 | Low |
| Bone marrow | 4.3 | Low |
| Kidney | 3.8 | Low |
| Lung | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.3 | High expression; associated with bone metastasis |
| MDA-MB-231 (breast cancer) | 22.1 | Very high; osteolytic phenotype |
| PC3 (prostate cancer) | 18.7 | High; promotes bone metastasis |
| HEK293 (embryonic kidney) | 1.2 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Likely loss-of-function; associated with skeletal dysplasia |
| c.217C>T (p.Arg73Cys) | missense | <0.01% | Uncertain significance; reported in HHM |
| Amplification (12p11.22) | copy number gain | 5-10% in breast cancer | Gain-of-function; increased PTHrP secretion |
Mutation functional classification
Loss of Function (LOF)
Rare missense/nonsense mutations (e.g., p.Met1?) that reduce PTHrP secretion or receptor binding; associated with skeletal dysplasia.
Gain of Function (GOF)
Gene amplification or promoter hypomethylation leading to PTHrP overexpression; common in HHM and bone-metastatic cancers.
Dominant Negative (DN)
Not reported for PTHLH; dominant-negative effects are described for its receptor PTH1R.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PTH/PTHrP signaling pathway (KEGG hsa04928)
• Osteoclast differentiation (KEGG hsa04380)
• Breast cancer bone metastasis (Reactome R-HSA-8878171)
• GPCR downstream signaling (Reactome R-HSA-388396)
Protein Summary
Parathyroid hormone-related protein (PTHrP) is a 141-amino-acid secreted protein that shares N-terminal homology with parathyroid hormone (PTH). It binds to the PTH1R G-protein-coupled receptor, activating cAMP/PKA and PLC/PKC pathways. PTHrP is critical for chondrocyte survival and bone elongation during development. In adults, it is expressed at low levels in skin, breast, and placenta. Pathologically, tumor-derived PTHrP causes humoral hypercalcemia of malignancy and facilitates osteolytic bone metastasis. The protein undergoes post-translational processing to generate multiple bioactive fragments (N-terminal, mid-region, C-terminal).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTHLH Knockout HEK293 Cell Line | EDJ-KQ3273 | Human | 5744 | Details Get a Quote |
| PTHLH Knockout A-549 Cell Line | EDJ-KQ24820 | Human | 5744 | Details Get a Quote |
| PTHLH Knockout HeLa Cell Line | EDJ-KQ24821 | Human | 5744 | Details Get a Quote |
| PTHLH Knockout HCT 116 Cell Line | EDJ-KQ71223 | Human | 5744 | Details Get a Quote |
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