CASR Gene: Calcium-Sensing Receptor
A comprehensive guide to the CASR gene, its function, associated diseases, expression, and mutations.
Gene Information Card
| Symbol | CASR |
|---|---|
| Full Name | Calcium-Sensing Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 3q13.33-q21.1 |
| NCBI Gene ID | 846 ncbi.nlm.nih.gov/gene/846 |
| Ensembl ID | ENSG00000036828 |
| UniProt ID | P41180 |
| OMIM ID | 601199 |
| HGNC ID | 1514 |
| Aliases | CAR, FHH, HHC, NSHPT, PCAR1, GPRC2A |
Description
The CASR gene encodes the calcium-sensing receptor (CaSR), a G-protein-coupled receptor that is critical for maintaining calcium homeostasis. It is primarily expressed in the parathyroid glands and kidneys, where it detects extracellular calcium levels and regulates parathyroid hormone (PTH) secretion and renal calcium reabsorption. Mutations in CASR cause a spectrum of calcium homeostasis disorders, including familial hypocalciuric hypercalcemia (FHH), neonatal severe hyperparathyroidism (NSHPT), and autosomal dominant hypocalcemia (ADH).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial Hypocalciuric Hypercalcemia (FHH) | Loss-of-function mutations in CASR reduce sensitivity to extracellular calcium, leading to elevated PTH and hypercalcemia with low urinary calcium excretion. | OMIM #145980; ClinVar |
| Neonatal Severe Hyperparathyroidism (NSHPT) | Biallelic loss-of-function mutations cause severe hypercalcemia and skeletal demineralization in neonates. | OMIM #239200; ClinVar |
| Autosomal Dominant Hypocalcemia (ADH) | Gain-of-function mutations increase receptor sensitivity, suppressing PTH and causing hypocalcemia with hypercalciuria. | OMIM #601198; ClinVar |
| Primary Hyperparathyroidism | Somatic mutations or altered expression of CASR may contribute to parathyroid adenomas, though germline mutations are rare. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Parathyroid Gland | High | High |
| Kidney | High | High |
| Thyroid | Medium | Medium |
| Brain | Low | Low |
| Gastrointestinal Tract | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Not detected | Used for recombinant expression studies |
| HeLa | Low | Endogenous expression minimal |
| MCF7 | Low | Breast cancer cell line, low expression |
| HCT116 | Low | Colon cancer cell line, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg185Gln | Missense | Rare (0.1% in general population) | Loss-of-function; associated with FHH |
| p.Arg227Leu | Missense | Rare | Loss-of-function; associated with NSHPT |
| p.Glu127Ala | Missense | Rare | Gain-of-function; associated with ADH |
| c.2533C>T (p.Arg845Cys) | Missense | Rare | Gain-of-function; associated with ADH |
Mutation functional classification
Loss of Function (LOF)
Reduces receptor sensitivity to calcium, leading to hypercalcemia and hypocalciuria (e.g., FHH, NSHPT).
Gain of Function (GOF)
Increases receptor sensitivity, causing hypocalcemia and hypercalciuria (e.g., ADH).
Dominant Negative (DN)
Some loss-of-function mutations may exert dominant-negative effects by forming inactive dimers, but this is not well established for CASR.
View complete mutation data：
Gene Ontology (GO)
| • G-protein coupled receptor activity | • calcium ion binding |
| • signal transduction | • cellular response to calcium ion |
| • plasma membrane |
Pathways
• GPCR downstream signaling (Gq/11
• PLC
• IP3
• Ca2+ release)
• Regulation of PTH secretion
• Renal calcium reabsorption
Protein Summary
The calcium-sensing receptor (CaSR) is a 1078-amino acid protein with a large extracellular domain, seven transmembrane helices, and an intracellular C-terminus. It forms homodimers and binds extracellular calcium, activating G-protein signaling pathways that modulate PTH release and renal calcium handling. Post-translational modifications include glycosylation and phosphorylation, which affect receptor trafficking and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASR Knockout HEK293 Cell Line | EDJ-KQ3089 | Human | 846 | Details Get a Quote |
| CASR Knockout HeLa Cell Line | EDJ-KQ52792 | Human | 846 | Details Get a Quote |
| CASR Knockout A-549 Cell Line | EDJ-KQ61262 | Human | 846 | Details Get a Quote |
| CASR Knockout HCT 116 Cell Line | EDJ-KQ69758 | Human | 846 | Details Get a Quote |
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