Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
41 authors.
Elena BlancoMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0000-0002-8150-5646
Carme CampsNational Institute for Health Research Oxford Biomedical Research Centre, University of Oxford , Oxford, UK.ORCID 0000-0003-0756-5752
Sameer BahalMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0000-0002-5541-3705
Mohit D KeraiMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0009-0002-2388-514X
Matteo P FerlaNational Institute for Health Research Oxford Biomedical Research Centre, University of Oxford , Oxford, UK.ORCID 0000-0002-5508-4673
Adam M RochussenCambridge Institute for Medical Research, University of Cambridge , Cambridge, UK.ORCID 0000-0001-9439-1206
Adam E HandelDepartment of Paediatrics and Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, UK.ORCID 0000-0001-8385-6346
Zainab M GolwalaMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0000-0002-8465-5746
Helena Spiridou GoncalvesMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0009-0002-6970-5618
Susanne KrickeSIHMDS-Haematology Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID 0000-0003-0791-2291
Fabian KleinDepartment of Paediatrics and Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-6208-8592
Fang ZhangMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0009-0006-1253-5987
Federica ZinghirinoMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0000-0001-8822-4217
Grace EvansMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0009-0009-9679-5760
Sabrina LizotHuman Lymphohematopoiesis Laboratory, Imagine Institute, INSERM UMR 1163, Université Paris Cité, Paris, France.ORCID 0000-0002-5092-5779
Maaike A A KustersDepartment of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID 0000-0001-7601-9822
Mildred A IroDepartment of Paediatric Infectious Diseases and Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.ORCID 0000-0002-9894-6149
Sanjay V PatelDepartment of Paediatric Infectious Diseases and Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.ORCID 0000-0001-6329-0496
Emma C MorrisDepartment of Immunology, Royal Free London Hospitals NHS Foundation Trust, London, UK.ORCID 0000-0003-4834-1130
Siobhan O BurnsDepartment of Immunology, Royal Free London Hospitals NHS Foundation Trust, London, UK.
Ruth RadcliffeDepartment of Immunology, University Hospitals of Leicester NHS Trust, Leicester, UK.ORCID 0009-0009-5922-183X
Pradeep VasudevanDepartment of Clinical Genetics, University Hospitals of Leicester NHS Trust, Leicester, UK.ORCID 0009-0002-6095-2030
Arthur PriceDepartment of Immunology, University Hospitals of Leicester NHS Trust, Leicester, UK.ORCID 0000-0002-5543-3837
Olivia GillhamDepartment of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, London, UK.ORCID 0000-0002-9799-8406
Gabriel E ValdebenitoDepartment of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, London, UK.ORCID 0000-0002-7169-6653
Grant S StewartInstitute of Cancer and Genomic Sciences, University of Birmingham , Birmingham, UK.ORCID 0000-0002-0960-3241
Austen WorthDepartment of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID 0000-0001-6803-7385
Stuart P AdamsSIHMDS-Haematology Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID 0000-0002-2650-2848
Michael DuchenDepartment of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, London, UK.ORCID 0000-0003-2548-4294
Isabelle AndréHuman Lymphohematopoiesis Laboratory, Imagine Institute, INSERM UMR 1163, Université Paris Cité, Paris, France.ORCID 0000-0002-3905-9910
Giorgia SantiliMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0000-0003-1776-1984
Kimberly C GilmourImmunology Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID 0000-0003-0285-3958
Georg A HolländerDepartment of Paediatrics and Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, UK.
E Graham DaviesMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0000-0001-6838-263X
Jenny C TaylorNational Institute for Health Research Oxford Biomedical Research Centre, University of Oxford , Oxford, UK.ORCID 0000-0003-3602-5704
Gillian M GriffithsCambridge Institute for Medical Research, University of Cambridge , Cambridge, UK.ORCID 0000-0003-0434-5842
Adrian J ThrasherMolecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0000-0002-6097-6115
Fatima Dhalla *Department of Paediatrics and Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, UK.ORCID 0000-0001-9244-2284
Alexandra Y Kreins *Molecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University College London , London, UK.ORCID 0000-0001-8748-5837
Funding
Biomedical Research CentreFundación Alfonso Martín EscuderoGreat Ormond Street Hospital Children's Charity U09822LetterOneMedical Research Council MR/S021930/1National Institute for Health and Care ResearchUCL Capital Equipment FundingUK Research and Innovation MR/L012758/1University College LondonWellcome TrustWellcome Trust 203141/Z/16/Z, 217112/Z/19/Z, 222096/Z/20/Z
6 · The paper itself
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 stages of thymic T cell development, and impaired function of peripheral T cells, including inadequate NF-κB- and NFAT-mediated, proliferative, and metabolic responses to activation. Pathogenicity is not due to haploinsufficiency, rather ITPR3 protein variants interfere with IP3R channel function leading to depletion of ER Ca2+ stores and blunted SOCE in T cells.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.
Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency. · full record | OpenQuestion