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

Nipith Charoenngam1, Phuuwadith Wattanachayakul2, Michael Mannstadt1

  • 1Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

The Journal of Clinical Endocrinology and Metabolism
|November 1, 2024
PubMed

Insights

A new database, CASRdb, catalogs 498 disease-causing variants of the calcium-sensing receptor (CASR) gene, aiding diagnoses of familial hypocalciuric hypercalcemia type I (FHH1) and autosomal dominant hypocalcemia type I (ADH1). This comprehensive resource enhances genetic testing for calcium metabolism disorders.

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.
Abstract

Keywords:
ADH1Bartter syndrome type VCASRFHH1autosomal dominant hypocalcemia type 1calcium-sensing receptorfamilial hypocalciuric hypercalcemia type 1neonatal severe hyperparathyroidism

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