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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CALCR
calcitonin receptor
Chromosome 7 · 7q21.3
NCBI Gene: 799Ensembl: ENSG00000004948.16HGNC: HGNC:1440UniProt: A0A0A0MSQ7
109PubMed Papers
20Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
calcitonin bindingamyloid-beta bindingcalcitonin gene-related peptide receptor activitypositive regulation of ERK1 and ERK2 cascadepostmenopausal osteoporosistype 2 diabetes mellitusosteoporosisosteitis deformans
✦AI Summary

CALCR (calcitonin receptor) is a G-protein-coupled receptor that plays critical roles in energy homeostasis, calcium regulation, and metabolic control. The receptor is highly expressed in brainstem regions including the dorsal vagal complex, area postrema, and nucleus of the solitary tract, where it mediates the effects of amylin and calcitonin on feeding behavior and body weight regulation 12. CALCR functions as part of amylin receptor complexes (AMY1-3) when combined with receptor activity-modifying proteins (RAMPs), enabling high-affinity amylin binding and downstream signaling through adenylyl cyclase activation 3. The receptor is essential for the anti-obesity effects of amylin analogs like cagrilintide, with CALCR-expressing neurons in the nucleus of the solitary tract showing sustained transcriptional responses that correlate with long-term weight loss 2. Beyond metabolic regulation, CALCR controls renal calcium handling, where decreased expression promotes hypercalciuria and calcium-containing kidney stone formation through dysregulated calcium excretion 4. Genetic variants in CALCR are associated with body mass index in large-scale human studies and kidney stone susceptibility 56. Additionally, CALCR shows aberrant overexpression in gastric cancer, where it interacts with ANTXR1 to promote tumor growth and metastasis via AKT signaling pathway activation 7.

Sources cited
1
CALCR is expressed in brainstem dorsal vagal complex neurons that regulate feeding behavior
PMID: 33767443
2
CALCR mediates cagrilintide's anti-obesity effects through sustained transcriptional changes in brainstem neurons
PMID: 39868309
3
CALCR forms amylin receptor complexes with RAMPs and mediates amylin's metabolic effects
PMID: 32634450
4
CALCR regulates renal calcium excretion and kidney stone formation
PMID: 39182194
5
CALCR genetic variants associate with body mass index in large-scale human studies
PMID: 34210852
6
CALCR variants are associated with kidney stone disease susceptibility
PMID: 36088585
7
CALCR is overexpressed in gastric cancer and promotes tumor growth via ANTXR1 interaction and AKT signaling
PMID: 40195530
Disease Associationsⓘ20
postmenopausal osteoporosisOpen Targets
0.54Moderate
type 2 diabetes mellitusOpen Targets
0.51Moderate
osteoporosisOpen Targets
0.50Moderate
osteitis deformansOpen Targets
0.47Moderate
HypercalcemiaOpen Targets
0.47Moderate
parathyroid diseaseOpen Targets
0.46Moderate
Abnormality of the skeletal systemOpen Targets
0.45Moderate
diabetes mellitusOpen Targets
0.43Moderate
smoking behaviorOpen Targets
0.42Moderate
type 1 diabetes mellitusOpen Targets
0.39Weak
Paget diseaseOpen Targets
0.37Weak
bone resorption diseaseOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.35Weak
obesityOpen Targets
0.35Weak
ocular hypotensionOpen Targets
0.33Weak
morbid obesityOpen Targets
0.31Weak
kidney diseaseOpen Targets
0.31Weak
osteoarthritisOpen Targets
0.29Weak
menopauseOpen Targets
0.28Weak
post-traumatic stress disorderOpen Targets
0.27Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets7
CALCITONINPhase III
Calcitonin receptor agonist
postmenopausal osteoporosis
CALCITONIN HUMANApproved
Calcitonin receptor agonist
Paget disease
CALCITONIN SALMONApproved
Calcitonin receptor agonist
osteoporosis
DAVALINTIDEPhase II
Amylin receptor AMY1, CALCR/RAMP1 agonist
obesity
PRAMLINTIDEApproved
Amylin receptor AMY2; CALCR/RAMP2 agonist
diabetes mellitus
PRAMLINTIDE ACETATEApproved
Amylin receptor AMY2; CALCR/RAMP2 agonist
SMC021Phase III
Calcitonin receptor agonist
osteoarthritis
Related Genes
ADMProtein interaction100%CALCBProtein interaction100%RAMP1Protein interaction100%RAMP2Protein interaction100%CALCRLProtein interaction99%TNFSF11Protein interaction96%
Tissue Expression6 tissues
Heart
100%
Brain
55%
Lung
30%
Bone Marrow
10%
Ovary
5%
Liver
0%
Gene Interaction Network
Click a node to explore
CALCRADMCALCBRAMP1RAMP2CALCRLTNFSF11
PROTEIN STRUCTURE
Preparing viewer…
PDB6PFO · 1.78 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.04LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.73 [0.53–1.04]
RankingsWhere CALCR stands among ~20K protein-coding genes
  • #4,347of 20,598
    Most Researched109 · top quartile
  • #415of 1,025
    FDA-Approved Drug Targets4
  • #10,346of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedCALCR
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Sequencing of 640,000 exomes identifies
PMID: 34210852
Science · 2021
1.00
2
A genetic map of the mouse dorsal vagal complex and its role in obesity.
PMID: 33767443
Nat Metab · 2021
0.90
3
A comprehensive spatio-cellular map of the human hypothalamus.
PMID: 39910307
Nature · 2025
0.80
4
A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide's Effects on Energy Balance.
PMID: 39868309
bioRxiv · 2025
0.70
5
Association of TRPV5, CASR, and CALCR genetic variants with kidney stone disease susceptibility in Egyptians through main effects and gene-gene interactions.
PMID: 36088585
Urolithiasis · 2022
0.60