CALCR Gene (Calcitonin Receptor): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the CALCR gene, its protein product, expression patterns, associated diseases, and mutations.
Gene Information Card
| Symbol | CALCR |
|---|---|
| Full Name | Calcitonin receptor |
| Gene Type | protein coding |
| Chromosomal Location | 7q21.3 |
| NCBI Gene ID | 799 ncbi.nlm.nih.gov/gene/799 |
| Ensembl ID | ENSG00000004948 |
| UniProt ID | P30988 |
| OMIM ID | 114131 |
| HGNC ID | 1440 |
| Aliases | CT-R, CTR, CRT-1 |
Description
The CALCR gene encodes the calcitonin receptor, a G protein-coupled receptor (GPCR) that binds calcitonin, a peptide hormone involved in calcium homeostasis and bone metabolism. The receptor is a member of the class B (secretin) GPCR family and is expressed in various tissues, including bone, kidney, and brain. Activation of CALCR by calcitonin leads to intracellular signaling cascades that regulate osteoclast activity, calcium reabsorption, and neuronal functions. Mutations and altered expression of CALCR have been implicated in several diseases, including osteoporosis, Paget's disease, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteoporosis | Reduced CALCR expression or function may impair calcitonin-mediated inhibition of osteoclasts, leading to increased bone resorption. | ClinVar, OMIM |
| Paget's disease of bone | Polymorphisms in CALCR have been associated with susceptibility to Paget's disease, possibly affecting receptor signaling and bone remodeling. | OMIM, PubMed |
| Medullary thyroid carcinoma | Overexpression of CALCR in medullary thyroid carcinoma cells may contribute to tumor growth and metastasis via autocrine calcitonin signaling. | COSMIC, PubMed |
| Hypercalciuria | Altered CALCR function in the kidney may disrupt calcium reabsorption, leading to hypercalciuria and kidney stone formation. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | Medium |
| Bone | 8.7 | Low |
| Brain | 6.2 | Low |
| Thyroid | 5.1 | Low |
| Lung | 2.4 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression |
| HEK293 (embryonic kidney) | 10.5 | Moderate expression |
| A549 (lung carcinoma) | 3.1 | Low expression |
| HepG2 (liver cancer) | 1.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1377C>T (p.Leu459Phe) | Missense | 0.1% (gnomAD) | May alter receptor signaling; associated with altered bone density in some studies. |
| c.1193G>A (p.Arg398His) | Missense | 0.05% (gnomAD) | Potential impact on ligand binding; reported in patients with hypercalciuria. |
| c.1340T>C (p.Ile447Thr) | Missense | 0.02% (gnomAD) | Rare variant; functional significance unknown. |
| c.1567C>T (p.Arg523Trp) | Missense | 0.01% (gnomAD) | Located in intracellular loop; may affect G protein coupling. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CALCR are rare but may lead to reduced receptor activity, impairing calcitonin signaling and contributing to conditions like osteoporosis or hypercalciuria.
Gain of Function (GOF)
Gain-of-function mutations have not been clearly documented; however, overexpression of CALCR in certain cancers may mimic a gain-of-function effect, promoting cell proliferation.
Dominant Negative (DN)
No dominant-negative mutations have been reported for CALCR; the receptor functions as a monomer or homodimer, and such mutations would likely be recessive.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • calcitonin binding |
| • peptide hormone binding | • signal transduction |
| • adenylate cyclase-activating G protein-coupled receptor signaling pathway | • cellular response to hormone stimulus |
| • positive regulation of cAMP-mediated signaling | • negative regulation of osteoclast differentiation |
| • calcium ion homeostasis |
Pathways
• Calcitonin signaling pathway
• GPCR downstream signaling
• cAMP/PKA signaling
• Regulation of bone resorption
• Calcium reabsorption in kidney
Protein Summary
The calcitonin receptor (CTR) is a 490-amino acid protein with seven transmembrane domains, characteristic of GPCRs. It is synthesized as a precursor and cleaved to form a mature receptor. The receptor is glycosylated and localized to the plasma membrane. Upon calcitonin binding, the receptor undergoes conformational changes that activate G proteins (Gs and Gq), leading to increased intracellular cAMP and calcium mobilization. CTR is involved in regulating osteoclast activity, renal calcium handling, and neuronal signaling. Alternative splicing generates multiple isoforms with varying affinities for calcitonin and signaling properties.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CALCR Knockout HEK293 Cell Line | EDJ-KQ1904 | Human | 799 | Details Get a Quote |
| CALCRL Knockout HEK293 Cell Line | EDJ-KQ2268 | Human | 10203 | Details Get a Quote |
| CALCR Knockout HeLa Cell Line | EDJ-KQ52781 | Human | 799 | Details Get a Quote |
| CALCRL Knockout HeLa Cell Line | EDJ-KQ55345 | Human | 10203 | Details Get a Quote |
| CALCR Knockout A-549 Cell Line | EDJ-KQ61249 | Human | 799 | Details Get a Quote |
| CALCRL Knockout A-549 Cell Line | EDJ-KQ63824 | Human | 10203 | Details Get a Quote |
| CALCR Knockout HCT 116 Cell Line | EDJ-KQ69746 | Human | 799 | Details Get a Quote |
| CALCRL Knockout HCT 116 Cell Line | EDJ-KQ72286 | Human | 10203 | Details Get a Quote |
