CALCR
protein-codingcalcitonin receptor, the group of MicroRNA protein coding host genes|Calcitonin receptors
Gene summary
This gene encodes a high affinity receptor for the peptide hormone calcitonin and belongs to a subfamily of seven transmembrane-spanning G protein-coupled receptors. The encoded protein is involved in maintaining calcium homeostasis and in regulating osteoclast-mediated bone resorption. Polymorphisms in this gene have been associated with variations in bone mineral density and onset of osteoporosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~150.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0005298
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CALCR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001742.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | 6 | |||
| missense | 54 | 6 | 1 | 61 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 57 | 9 | 4 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001733.1 | 12 | MANE Select | |
| Ensembl | ENSP00000389295.1 | 12 | MANE Select | |
| RefSeq | NP_001158209.2 | 13 | Standard | |
| RefSeq | NP_001158210.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Osteoclast differentiation - Homo sapiens (human)
- RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway
- GPCRs, Class B Secretin-like
- Signaling by GPCR
Biological Process
- cell surface receptor signaling pathway
- G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- activation of adenylate cyclase activity
- positive regulation of cytosolic calcium ion concentration
Molecular Function
- amyloid-beta binding
- calcitonin gene-related peptide receptor activity
- calcitonin receptor activity
- protein binding
- calcitonin binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- axon
- amylin receptor complex 1
- amylin receptor complex 2
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359558
- Coding exons
- 14
- Length
- 150244
- Individuals with no LoFs
- 125683
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 61
- Defined
- 125744
- p
- 0.000243
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.515 | 263 | 288 | 0.915 | 0.0000158 | 3343 |
| Missense (PolyPhen) | 105 | 117.34 | 0.8948 | 1434 | ||
| Synonymous | 0.239 | 102 | 105 | 0.970 | 0.00000618 | 915 |
| Loss of Function | 1.86 | 18 | 28.8 | 0.625 | 0.00000155 | 323 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00030 | 0.00030 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This is a receptor for calcitonin. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The calcitonin receptor is thought to couple to the heterotrimeric guanosine triphosphate-binding protein that is sensitive to cholera toxin.;
Recessive Scores
- pRec
- 0.475
Intolerance Scores
- LoFtool
- 0.939
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.718
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |