CASRdb: A Publicly Accessible Comprehensive Database for Disease-Associated Calcium-Sensing Receptor Variants

Area of Science:

• Genetics
• Molecular Biology
• Biochemistry

Background:

• Genetic testing of the calcium-sensing receptor (CASR) gene is essential for diagnosing familial hypocalciuric hypercalcemia type I (FHH1) and autosomal dominant hypocalcemia type I (ADH1).
• A comprehensive and accessible database of disease-causing CASR gene variants is needed to support clinical diagnostics and research.

Purpose of the Study:

• To create a publicly accessible, comprehensive database of disease-causing variants within the CASR gene.
• To consolidate information on CASR variants associated with calcium metabolism disorders.

Main Methods:

• Systematic literature review of Embase and PubMed databases (up to March 2023) for CASR variants.
• Data retrieval from ClinVar and LOVD databases for pathogenic (P) or likely pathogenic (LP) variants.
• Inclusion of variants of uncertain significance (VUS) only if reported in literature; exclusion of benign variants.

Main Results:

• A total of 498 CASR variants were identified and compiled.
• 121 variants (24.3%) were associated with ADH1, and 377 variants (75.7%) were associated with FHH1.
• A significant proportion of identified variants, particularly inactivating ones, were not previously documented in ClinVar/LOVD.

Conclusions:

• CASRdb has been developed, providing a centralized repository of CASR variants linked to calcium metabolism disorders.
• The database contains a substantially larger number of disease-associated variants compared to existing resources, underscoring its comprehensive nature.
• The CASRdb website is now available at http://casrdb.mgh.harvard.edu for public access.