{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:11:30Z","timestamp":1790964690112,"version":"4.1.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Genetic testing of the calcium-sensing receptor (CASR) gene is crucial for confirming diagnoses of familial hypocalciuric hypercalcemia type I (FHH1) and autosomal dominant hypocalcemia type I (ADH1). Therefore, we created a publicly accessible comprehensive database of the disease-causing variants of the CASR gene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Acquisition<\/jats:title>\n                    <jats:p>We used 2 sources for variant reports: (1) we conducted a systematic review in the Embase and PubMed databases from inception to March 2023, using search strategies associated with CASR. We identified all articles reporting CASR variants associated with disorders of calcium metabolism. (2) Additionally, data associated with pathogenic (P) or likely pathogenic (LP) variants in the ClinVar and LOVD databases were retrieved. Benign or likely benign variants were excluded. Variants of uncertain significance (VUS) were included only if they were reported in the literature. We generated a library of CASR variants associated with phenotypes, which has been made available on a website.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Synthesis<\/jats:title>\n                    <jats:p>We identified a total of 498 variants, of which 121 (24.3%) were associated with ADH1 and 377 (75.7%) with FHH1. Most included variants were identified from the literature (117 activating and 352 inactivating variants), and the majority of these were not documented in ClinVar\/LOVD (73\/117, 62.4% activating variants; 207\/352, 58.8% inactivating variants).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We developed CASRdb, a database that compiles information on all CASR variants associated with disorders of calcium metabolism from existing literature and genomic databases. Our database stands out due to the substantially higher number of disease-associated variants it contains, highlighting its comprehensive nature. The website is available at http:\/\/casrdb.mgh.harvard.edu.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgae769","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T02:05:48Z","timestamp":1730253948000},"page":"297-302","source":"Crossref","is-referenced-by-count":12,"title":["CASRdb: A Publicly Accessible Comprehensive Database for Disease-Associated Calcium-Sensing Receptor Variants"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-6180","authenticated-orcid":false,"given":"Nipith","family":"Charoenngam","sequence":"first","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuuwadith","family":"Wattanachayakul","sequence":"additional","affiliation":[{"name":"Department of Medicine, Jefferson Einstein Hospital , Philadelphia, PA 19141 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-9778","authenticated-orcid":false,"given":"Michael","family":"Mannstadt","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"issue":"1","key":"2025012110280636500_dgae769-B1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41574-018-0115-0","article-title":"The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases","volume":"15","author":"Hannan","year":"2018","journal-title":"Nat Rev Endocrinol"},{"issue":"1","key":"2025012110280636500_dgae769-B2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1152\/physrev.2001.81.1.239","article-title":"Extracellular calcium sensing and extracellular calcium signaling","volume":"81","author":"Brown","year":"2001","journal-title":"Physiol Rev"},{"issue":"5","key":"2025012110280636500_dgae769-B3","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1111\/j.1582-4934.2007.00096.x","article-title":"Structure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators","volume":"11","author":"Hu","year":"2007","journal-title":"J Cell Mol Med"},{"issue":"23","key":"2025012110280636500_dgae769-B4","doi-asserted-by":"crossref","first-page":"eabg1483","DOI":"10.1126\/sciadv.abg1483","article-title":"Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor","volume":"7","author":"Wen","year":"2021","journal-title":"Sci Adv"},{"issue":"8001","key":"2025012110280636500_dgae769-B5","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41586-024-07055-2","article-title":"Allosteric modulation and G-protein selectivity of the Ca2+-sensing receptor","volume":"626","author":"He","year":"2024","journal-title":"Nature"},{"key":"2025012110280636500_dgae769-B6","doi-asserted-by":"crossref","first-page":"e68578","DOI":"10.7554\/eLife.68578","article-title":"Structural insights into the activation of human calcium-sensing receptor","volume":"10","author":"Chen","year":"2021","journal-title":"Elife"},{"issue":"7867","key":"2025012110280636500_dgae769-B7","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41586-021-03691-0","article-title":"Asymmetric activation of the calcium-sensing receptor homodimer","volume":"595","author":"Gao","year":"2021","journal-title":"Nature"},{"issue":"51","key":"2025012110280636500_dgae769-B8","doi-asserted-by":"crossref","first-page":"e2115849118","DOI":"10.1073\/pnas.2115849118","article-title":"Symmetric activation and modulation of the human calcium-sensing receptor","volume":"118","author":"Park","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"13","key":"2025012110280636500_dgae769-B9","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1056\/NEJMc2302708","article-title":"Efficacy and safety of encaleret in autosomal dominant hypocalcemia type 1","volume":"389","author":"Gafni Rachel","year":"2023","journal-title":"N Engl J Med"},{"issue":"2","key":"2025012110280636500_dgae769-B10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/humu.20067","article-title":"Casrdb: calcium-sensing receptor locus-specific database for mutations causing familial (benign) hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia","volume":"24","author":"Pidasheva","year":"2004","journal-title":"Hum Mutat"},{"key":"2025012110280636500_dgae769-B11"},{"key":"2025012110280636500_dgae769-B12","doi-asserted-by":"crossref","unstructured":"Charoenngam N, Wattanachayakul P, Mannstadt M. 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