{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Blanco E"],"funding":["LetterOne","Cancer Research UK","Great Ormond Street Hospital Children's Charity","Biomedical Research Centre","Medical Research Council","University College London","UCL Capital Equipment Funding","Fundación Alfonso Martín Escudero","National Institute for Health and Care Research","Wellcome Trust","UK Research and Innovation","Great Ormond Street Hospital Children's Charity"],"pagination":["e20220979"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11577440"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["222(1)"],"pubmed_abstract":["The importance of calcium (Ca2+) as a second messenger in T cell signaling is exemplified by genetic deficiencies of STIM1 and ORAI1, which abolish store-operated Ca2+ entry (SOCE) resulting in combined immunodeficiency (CID). We report five unrelated patients with de novo missense variants in ITPR3, encoding a subunit of the inositol 1,4,5-trisphosphate receptor (IP3R), which forms a Ca2+ channel in the endoplasmic reticulum (ER) membrane responsible for the release of ER Ca2+ required to trigger SOCE, and for Ca2+ transfer to other organelles. The patients presented with CID, abnormal T cell Ca2+ homeostasis, incompletely penetrant ectodermal dysplasia, and multisystem disease. Their predominant T cell immunodeficiency is characterized by significant T cell lymphopenia, defects in late s"],"journal":["The Journal of experimental medicine"],"pubmed_title":["Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency."],"pmcid":["PMC11577440"],"funding_grant_id":["203141/Z/16/Z","U09822","MR/L012758/1","MR/S021930/1","203141/Z/16/Z, 217112/Z/19/Z, 222096/Z/20/Z","23303","217112/Z/19/Z","222096/Z/20/Z"],"pubmed_authors":["Zhang F","Valdebenito GE","Santili G","Taylor JC","Rochussen AM","Burns SO","Kerai MD","Davies EG","Stewart GS","Duchen M","Bahal S","Adams SP","Morris EC","Radcliffe R","Patel SV","Adams DJ","Griffiths GM","Ferla MP","Blanco E","Vasudevan P","Zinghirino F","Golwala ZM","Lizot S","Iro MA","Evans G","Gillham O","Dhalla F","Camps C","Handel AE","Gilmour KC","Spiridou Goncalves H","Keane TM","Worth A","Klein F","Thrasher AJ","Kusters MAA","Andre I","Price A","Kricke S","Hollander GA","Kreins AY"],"additional_accession":[]},"is_claimable":false,"name":"Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency.","description":"The importance of calcium (Ca2+) as a second messenger in T cell signaling is exemplified by genetic deficiencies of STIM1 and ORAI1, which abolish store-operated Ca2+ entry (SOCE) resulting in combined immunodeficiency (CID). We report five unrelated patients with de novo missense variants in ITPR3, encoding a subunit of the inositol 1,4,5-trisphosphate receptor (IP3R), which forms a Ca2+ channel in the endoplasmic reticulum (ER) membrane responsible for the release of ER Ca2+ required to trigger SOCE, and for Ca2+ transfer to other organelles. The patients presented with CID, abnormal T cell Ca2+ homeostasis, incompletely penetrant ectodermal dysplasia, and multisystem disease. Their predominant T cell immunodeficiency is characterized by significant T cell lymphopenia, defects in late s","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-03T01:08:20.238Z","creation":"2026-04-22T03:11:46.092Z"},"accession":"S-EPMC11577440","cross_references":{"pubmed":["39560673"],"doi":["10.1084/jem.20220979"]}}