{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T22:58:08Z","timestamp":1794351488643,"version":"4.9.0"},"reference-count":94,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:00:00Z","timestamp":1692662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PID2019-104084GB-C21","award":["IB20007"],"award-info":[{"award-number":["IB20007"]}]},{"name":"PID2019-104084GB-C21","award":["GR21008"],"award-info":[{"award-number":["GR21008"]}]},{"name":"PID2019-104084GB-C22","award":["IB20007"],"award-info":[{"award-number":["IB20007"]}]},{"name":"PID2019-104084GB-C22","award":["GR21008"],"award-info":[{"award-number":["GR21008"]}]},{"name":"PID2022-136279NB-C21","award":["IB20007"],"award-info":[{"award-number":["IB20007"]}]},{"name":"PID2022-136279NB-C21","award":["GR21008"],"award-info":[{"award-number":["GR21008"]}]},{"name":"PID2022-136279NB-C22","award":["IB20007"],"award-info":[{"award-number":["IB20007"]}]},{"name":"PID2022-136279NB-C22","award":["GR21008"],"award-info":[{"award-number":["GR21008"]}]},{"name":"Junta de Extremadura-Fondo Europeo de Desarrollo Regional","award":["IB20007"],"award-info":[{"award-number":["IB20007"]}]},{"name":"Junta de Extremadura-Fondo Europeo de Desarrollo Regional","award":["GR21008"],"award-info":[{"award-number":["GR21008"]}]},{"name":"Agencia Estatal de Investigaci\u00f3n","award":["IB20007"],"award-info":[{"award-number":["IB20007"]}]},{"name":"Agencia Estatal de Investigaci\u00f3n","award":["GR21008"],"award-info":[{"award-number":["GR21008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The STIM family of proteins plays a crucial role in a plethora of cellular functions through the regulation of store-operated Ca2+ entry (SOCE) and, thus, intracellular calcium homeostasis. The two members of the mammalian STIM family, STIM1 and STIM2, are transmembrane proteins that act as Ca2+ sensors in the endoplasmic reticulum (ER) and, upon Ca2+ store discharge, interact with and activate the Orai\/CRACs in the plasma membrane. Dysregulation of Ca2+ signaling leads to the pathogenesis of a variety of human diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and immune disorders. Therefore, understanding the mechanisms underlying Ca2+ signaling pathways is crucial for developing therapeutic strategies targeting these diseases. This review focuses on several rare conditions associated with STIM1 mutations that lead to either gain- or loss-of-function, characterized by myopathy, hematological and immunological disorders, among others, and due to abnormal activation of CRACs. In addition, we summarize the current evidence concerning STIM2 allele duplication and deletion associated with language, intellectual, and developmental delay, recurrent pulmonary infections, microcephaly, facial dimorphism, limb anomalies, hypogonadism, and congenital heart defects.<\/jats:p>","DOI":"10.3390\/biom13091284","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T07:25:24Z","timestamp":1692775524000},"page":"1284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Ca2+ Sensor STIM in Human Diseases"],"prefix":"10.3390","volume":"13","author":[{"given":"Alejandro","family":"Berna-Erro","sequence":"first","affiliation":[{"name":"Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Sanchez-Collado","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology and Biophysics, University of Seville, 41004 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-3893","authenticated-orcid":false,"given":"Joel","family":"Nieto-Felipe","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Macias-Diaz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2067-2627","authenticated-orcid":false,"given":"Pedro C.","family":"Redondo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1877-7438","authenticated-orcid":false,"given":"Tarik","family":"Smani","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology and Biophysics, University of Seville, 41004 Seville, Spain"},{"name":"Group of Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Rocio, University of Seville, Spanish National Research Council (CSIC), 41004 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5234-1478","authenticated-orcid":false,"given":"Jose J.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4575-8264","authenticated-orcid":false,"given":"Isaac","family":"Jardin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9749-2325","authenticated-orcid":false,"given":"Juan A.","family":"Rosado","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrm1155","article-title":"Calcium signalling: Dynamics, homeostasis and remodelling","volume":"4","author":"Berridge","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0143-4160(86)90026-6","article-title":"A model for receptor-regulated calcium entry","volume":"7","author":"Putney","year":"1986","journal-title":"Cell Calcium"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ceca.2019.03.004","article-title":"CRAC channels and disease\u2014From human CRAC channelopathies and animal models to novel drugs","volume":"80","author":"Feske","year":"2019","journal-title":"Cell Calcium"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1016\/j.bbamcr.2015.10.003","article-title":"STIM and calcium channel complexes in cancer","volume":"1863","author":"Jardin","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BST20110766","article-title":"Calcium signalling remodelling and disease","volume":"40","author":"Berridge","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"980","DOI":"10.2741\/202","article-title":"Origins of the concept of store-operated calcium entry","volume":"3","author":"Putney","year":"2011","journal-title":"Front. Biosci. Schol. Ed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0922-4106(94)90046-9","article-title":"Inhibition of capacitative Ca2+ entry by a Cl- channel blocker in human endothelial cells","volume":"269","author":"Gericke","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-3-319-55858-5_9","article-title":"Store-Operated Calcium Entry: An Historical Overview","volume":"981","author":"Putney","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/jcp.20399","article-title":"Store-operated Ca2+ entry: Vesicle fusion or reversible trafficking and de novo conformational coupling?","volume":"205","author":"Rosado","year":"2005","journal-title":"J. Cell Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.tibs.2005.05.009","article-title":"CIF and other mysteries of the store-operated Ca2+-entry pathway","volume":"30","author":"Bolotina","year":"2005","journal-title":"Trends Biochem. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0960-9822(06)00259-4","article-title":"Calcium release and influx colocalize to the endoplasmic reticulum","volume":"7","author":"Jaconi","year":"1997","journal-title":"Curr. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/nature04147","article-title":"STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane","volume":"437","author":"Zhang","year":"2005","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1083\/jcb.200502019","article-title":"STIM1, an essential and conserved component of store-operated Ca2+ channel function","volume":"169","author":"Roos","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nature05122","article-title":"Orai1 is an essential pore subunit of the CRAC channel","volume":"443","author":"Prakriya","year":"2006","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature04702","article-title":"A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function","volume":"441","author":"Feske","year":"2006","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1083\/jcb.200604015","article-title":"The elementary unit of store-operated Ca2+ entry: Local activation of CRAC channels by STIM1 at ER-plasma membrane junctions","volume":"174","author":"Luik","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/978-3-030-12457-1_23","article-title":"Review: Structure and Activation Mechanisms of CRAC Channels","volume":"1131","author":"Butorac","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/ncb1842","article-title":"SOAR and the polybasic STIM1 domains gate and regulate Orai channels","volume":"11","author":"Yuan","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8421","DOI":"10.1074\/jbc.C800229200","article-title":"A Cytosolic Homomerization and a Modulatory Domain within STIM1 C Terminus Determine Coupling to ORAI1 Channels","volume":"284","author":"Muik","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"C643","DOI":"10.1152\/ajpcell.00007.2016","article-title":"Molecular mechanisms of STIM\/Orai communication","volume":"310","author":"Derler","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev-physiol-052521-013426","article-title":"Physiological Functions of CRAC Channels","volume":"84","author":"Emrich","year":"2022","journal-title":"Annu. Rev. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1159\/000015341","article-title":"Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD","volume":"86","author":"Sabbioni","year":"1999","journal-title":"Cytogenet. Cell Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1016\/j.cellsig.2013.01.025","article-title":"The polybasic lysine-rich domain of plasma membrane-resident STIM1 is essential for the modulation of store-operated divalent cation entry by extracellular calcium","volume":"25","author":"Jardin","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12257","DOI":"10.1074\/jbc.M110.190694","article-title":"STIM1 and STIM2 are located in the acidic Ca2+ stores and associates with Orai1 upon depletion of the acidic stores in human platelets","volume":"286","author":"Zbidi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1073\/pnas.0510050103","article-title":"STIM1 has a plasma membrane role in the activation of store-operated Ca(2+) channels","volume":"103","author":"Spassova","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-3-319-57732-6_4","article-title":"The STIM-Orai Pathway: The Interactions Between STIM and Orai","volume":"993","author":"Fahrner","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.cell.2008.08.006","article-title":"Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry","volume":"135","author":"Stathopulos","year":"2008","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2007.11.039","article-title":"STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels","volume":"131","author":"Brandman","year":"2007","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nature07065","article-title":"Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation","volume":"454","author":"Luik","year":"2008","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1073\/pnas.1015125108","article-title":"Auto-inhibitory role of the EF-SAM domain of STIM proteins in store-operated calcium entry","volume":"108","author":"Zheng","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"35855","DOI":"10.1074\/jbc.M608247200","article-title":"Stored Ca2+ depletion-induced oligomerization of stromal interaction molecule 1 (STIM1) via the EF-SAM region: An initiation mechanism for capacitive Ca2+ entry","volume":"281","author":"Stathopulos","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7826","DOI":"10.1038\/ncomms8826","article-title":"Inside-out Ca(2+) signalling prompted by STIM1 conformational switch","volume":"6","author":"Ma","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e66194","DOI":"10.7554\/eLife.66194","article-title":"Conformational dynamics of auto-inhibition in the ER calcium sensor STIM1","volume":"10","author":"Qiu","year":"2021","journal-title":"Elife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.cell.2009.02.014","article-title":"STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1","volume":"136","author":"Park","year":"2009","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33231","DOI":"10.1074\/jbc.M114.610022","article-title":"A coiled-coil clamp controls both conformation and clustering of stromal interaction molecule 1 (STIM1)","volume":"289","author":"Fahrner","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/s41467-018-03062-w","article-title":"A dual mechanism promotes switching of the Stormorken STIM1 R304W mutant into the activated state","volume":"9","author":"Fahrner","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41589-020-00672-8","article-title":"Interhelical interactions within the STIM1 CC1 domain modulate CRAC channel activation","volume":"17","author":"Rathner","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1038\/ncomms3963","article-title":"STIM1\/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry","volume":"4","author":"Stathopulos","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1038\/ncomms4183","article-title":"Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site","volume":"5","author":"Wang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5657","DOI":"10.1073\/pnas.1118947109","article-title":"Structural and mechanistic insights into the activation of Stromal interaction molecule 1 (STIM1)","volume":"109","author":"Yang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/humu.22544","article-title":"A dominant STIM1 mutation causes Stormorken syndrome","volume":"35","author":"Misceo","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"jcs237354","DOI":"10.1242\/jcs.237354","article-title":"The inactivation domain of STIM1 acts through intramolecular binding to the coiled-coil domain in the resting state","volume":"133","author":"Lee","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1083\/jcb.201711151","article-title":"EB1 binding restricts STIM1 translocation to ER-PM junctions and regulates store-operated Ca(2+) entry","volume":"217","author":"Chang","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.cell.2009.04.065","article-title":"An EB1-binding motif acts as a microtubule tip localization signal","volume":"138","author":"Honnappa","year":"2009","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sallinger, M., Grabmayr, H., Humer, C., Bonhenry, D., Romanin, C., Schindl, R., and Derler, I. (2023). Activation mechanisms and structural dynamics of STIM proteins. J. Physiol., ahead of print.","DOI":"10.1113\/JP283828"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1399-0004.1985.tb02209.x","article-title":"A new syndrome: Thrombocytopathia, muscle fatigue, asplenia, miosis, migraine, dyslexia and ichthyosis","volume":"28","author":"Stormorken","year":"1985","journal-title":"Clin. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1111\/j.1538-7836.2008.03111.x","article-title":"Thrombin induces activation and translocation of Bid, Bax and Bak to the mitochondria in human platelets","volume":"6","author":"Lopez","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1182\/blood.V97.9.2648","article-title":"Fibrinogen binding to the integrin alpha(IIb)beta(3) modulates store-mediated calcium entry in human platelets","volume":"97","author":"Rosado","year":"2001","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1002\/humu.22621","article-title":"Gain-of-Function Mutation in STIM1 (P.R304W) Is Associated with Stormorken Syndrome","volume":"35","author":"Morin","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1055\/s-0038-1649920","article-title":"Studies on the haemostatic defect in a complicated syndrome. An inverse Scott syndrome platelet membrane abnormality?","volume":"74","author":"Stormorken","year":"1995","journal-title":"Thromb. Haemost."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1172\/JCI32312","article-title":"An EF hand mutation in Stim1 causes premature platelet activation and bleeding in mice","volume":"117","author":"Grosse","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.1073\/pnas.1312520111","article-title":"Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis","volume":"111","author":"Nesin","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1038\/emboj.2011.79","article-title":"STIM1 couples to ORAI1 via an intramolecular transition into an extended conformation","volume":"30","author":"Muik","year":"2011","journal-title":"EMBO J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ceca.2018.10.001","article-title":"STIM1 R304W causes muscle degeneration and impaired platelet activation in mice","volume":"76","author":"Gamage","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"522513","DOI":"10.3389\/fneur.2021.522513","article-title":"Stormorken Syndrome Caused by a Novel STIM1 Mutation: A Case Report","volume":"12","author":"Jiang","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ceca.2018.07.008","article-title":"Gain-of-function mutations in STIM1 and ORAI1 causing tubular aggregate myopathy and Stormorken syndrome","volume":"76","author":"Bohm","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102347","DOI":"10.1016\/j.coph.2022.102347","article-title":"Store-operated calcium entry: From physiology to tubular aggregate myopathy","volume":"68","author":"Protasi","year":"2023","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lee, J.M., and Noguchi, S. (2016). Calcium Dyshomeostasis in Tubular Aggregate Myopathy. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111952"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/nyas.12938","article-title":"Diseases caused by mutations in ORAI1 and STIM1","volume":"1356","author":"Lacruz","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ajhg.2012.12.007","article-title":"Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy","volume":"92","author":"Bohm","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1136\/jmedgenet-2014-102623","article-title":"Clinical, histological and genetic characterisation of patients with tubular aggregate myopathy caused by mutations in STIM1","volume":"51","author":"Bohm","year":"2014","journal-title":"J. Med. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1007\/s00415-014-7287-x","article-title":"Childhood onset tubular aggregate myopathy associated with de novo STIM1 mutations","volume":"261","author":"Hedberg","year":"2014","journal-title":"J. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.nmd.2015.04.005","article-title":"50 years to diagnosis: Autosomal dominant tubular aggregate myopathy caused by a novel STIM1 mutation","volume":"25","author":"Walter","year":"2015","journal-title":"Neuromuscul. Disord."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1002\/humu.23338","article-title":"Identification and characterization of three novel mutations in the CASQ1 gene in four patients with tubular aggregate myopathy","volume":"38","author":"Barone","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/0953710031000080044","article-title":"Giant electron-dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: An inherited thrombocytopenic disorder","volume":"14","author":"White","year":"2003","journal-title":"Platelets"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/095371002100057550","article-title":"Giant electron-dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: An inherited thrombocytopenic disorder I. Megakaryocytes","volume":"14","author":"White","year":"2003","journal-title":"Platelets"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/09537100310001594534","article-title":"Giant electron dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: An inherited thrombocytopenic disorder IV. Ultrastructural cytochemistry and analytical electron microscopy","volume":"14","author":"White","year":"2003","journal-title":"Platelets"},{"key":"ref_68","first-page":"305","article-title":"Giant electron dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: An inherited thrombocytopenic disorder III. Platelet analytical electron microscopy","volume":"14","author":"White","year":"2003","journal-title":"Platelets"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3109\/09537104.2010.524323","article-title":"The York Platelet Syndrome: A third case","volume":"22","author":"White","year":"2011","journal-title":"Platelets"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.ymgme.2014.12.307","article-title":"York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1","volume":"114","author":"Markello","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_71","first-page":"5130143","article-title":"Myopathy in the York Platelet Syndrome: An Underrecognized Complication","volume":"2018","author":"Roman","year":"2018","journal-title":"Case Rep. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/mus.27391","article-title":"Expanding the clinical and genetic spectrum of pathogenic variants in STIM1","volume":"64","author":"Ticci","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1083\/jcb.201012157","article-title":"STIM1L is a new actin-binding splice variant involved in fast repetitive Ca2+ release","volume":"194","author":"Darbellay","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"102605","DOI":"10.1016\/j.ceca.2022.102605","article-title":"STIM1 and ORAI1 mutations leading to tubular aggregate myopathies are sensitive to the Store-operated Ca(2+)-entry modulators CIC-37 and CIC-39","volume":"105","author":"Riva","year":"2022","journal-title":"Cell Calcium"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/jcpt.13322","article-title":"A first-in-human study to evaluate the safety, tolerability and pharmacokinetics of RP3128, an oral calcium release-activated calcium (CRAC) channel modulator in healthy volunteers","volume":"46","author":"Barde","year":"2021","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/MPA.0000000000001793","article-title":"Auxora for the Treatment of Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome: Clinical Development of a Calcium Release-Activated Calcium Channel Inhibitor","volume":"50","author":"Bruen","year":"2021","journal-title":"Pancreas"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00424-009-0777-5","article-title":"CRAC channelopathies","volume":"460","author":"Feske","year":"2010","journal-title":"Pflugers Arch."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1056\/NEJMoa0900082","article-title":"STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity","volume":"360","author":"Picard","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1084\/jem.20101597","article-title":"Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma","volume":"207","author":"Byun","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/nrc2888","article-title":"Kaposi\u2019s sarcoma and its associated herpesvirus","volume":"10","author":"Mesri","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.jaci.2015.03.009","article-title":"A novel hypomorphic mutation in STIM1 results in a late-onset immunodeficiency","volume":"136","author":"Schaballie","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.4049\/jimmunol.1102507","article-title":"Antiviral and regulatory T cell immunity in a patient with stromal interaction molecule 1 deficiency","volume":"188","author":"Fuchs","year":"2012","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6206","DOI":"10.1073\/pnas.1418852112","article-title":"Missense mutation in immunodeficient patients shows the multifunctional roles of coiled-coil domain 3 (CC3) in STIM1 activation","volume":"112","author":"Maus","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"94S","DOI":"10.1177\/0022034514527971","article-title":"STIM1 and SLC24A4 Are Critical for Enamel Maturation","volume":"93","author":"Wang","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"102157","DOI":"10.1016\/j.jbc.2022.102157","article-title":"Mapping interactions between the CRAC activation domain and CC1 regulating the activity of the ER Ca(2+) sensor STIM1","volume":"298","author":"Shrestha","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/cge.13959","article-title":"A novel bi-allelic loss-of-function mutation in STIM1 expands the phenotype of STIM1-related diseases","volume":"100","author":"Salvi","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Di, J., Yenwongfai, L., Rieger, H.T., Zhang, S., and Wei, S. (2023). Familial 4p Interstitial Deletion Provides New Insights and Candidate Genes Underlying This Rare Condition. Genes, 14.","DOI":"10.3390\/genes14030635"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.gene.2013.07.063","article-title":"Prenatal diagnosis and molecular cytogenetic characterization of a de novo proximal interstitial deletion of chromosome 4p (4p15.2-->p14)","volume":"529","author":"Chen","year":"2013","journal-title":"Gene"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1002\/acn3.51040","article-title":"A familial t(4;8) translocation segregates with epilepsy and migraine with aura","volume":"7","author":"Crippa","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"17625","DOI":"10.1038\/s41598-017-17762-8","article-title":"Stim2-Eb3 Association and Morphology of Dendritic Spines in Hippocampal Neurons","volume":"7","author":"Pchitskaya","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1113\/JP273889","article-title":"Role of STIM2 in cell function and physiopathology","volume":"595","author":"Jardin","year":"2017","journal-title":"J. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1159\/000454698","article-title":"A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay","volume":"150","author":"Liang","year":"2016","journal-title":"Cytogenet. Genome Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/ajmg.1320550203","article-title":"Syndrome of proximal interstitial deletion 4p15: Report of three cases and review of the literature","volume":"55","author":"Chitayat","year":"1995","journal-title":"Am. J. Med. Genet."},{"key":"ref_94","first-page":"ra67","article-title":"STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic neuronal cell death","volume":"2","author":"Braun","year":"2009","journal-title":"Sci. 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