ArticleNature immunology2017
BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00246857 (Screening Protocol for Genetic Diseases of Lymphocyte Homeostasis and Programmed Cell Death), which is not on this map. Cited by 92 papers.
0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
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.
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.
Screening Protocol for Genetic Diseases of Lymphocyte Homeostasis and Programmed Cell Death
Who cites it
92 citing papers in PubMed, 149 citations in OpenAlex.
- Selective persistence of HIV-1-infected T cell clones can occur through immune reprogramming driven by defective, transcriptionally active proviruses.PLoS pathogens · 2026Article
- Bidirectional regulation by BACH2 coordinates systemic CXCR5- vs. CXCR5+ CD4+ T cell differentiation.The Journal of experimental medicine · 2026Article
- Review
- Rare variants in genes related to inborn errors of immunity in patients with rheumatoid arthritis and secondary immunodeficiency.RMD open · 2026Article
- The utility of CNV analysis in identifying the molecular etiology of pediatric epilepsy patients.Pediatric research · 2026Article
- Article
- BACH transcription factors in diseases of the exocrine and endocrine pancreas: effects, mechanisms, and clinical implications.Frontiers in medicine · 2026Review
- Disseminated BCG disease and recurrent pulmonary infections in a child with trisomy 21 carrying a novelFrontiers in medicine · 2026Article
- Inborn errors of regulatory T-cell differentiation and function.The Journal of allergy and clinical immunology · 2025Review
- Two novel BACH2 variants presenting as Still's disease with renal thrombotic microangiopathy and immunodeficiency with recurrent infections.Rheumatology international · 2025Article
- Guardians of silence: transcriptional networks in T cell quiescence.Experimental & molecular medicine · 2025Review
- Pathological IgE Production in Inborn Errors of Immunity and Beyond.Immunological reviews · 2025Review
- Inborn errors of immunity underlie clonal T cell expansions in large granular lymphocyte leukemia.The Journal of clinical investigation · 2025Article
- Autoimmune enteropathy associated with T cell large granular lymphocytic leukemia in a patient withJournal of gastrointestinal oncology · 2025Article
- The epigenetic landscape of fate decisions in T cells.Nature immunology · 2025Review
- Molecular analysis of acute pyelonephritis-excessive innate and attenuated adaptive immunity.Life science alliance · 2025Article
- Heme regulates protein interactions and phosphorylation of BACH2 intrinsically disordered region in humoral response.iScience · 2025Article
- Prevalence of pathogenic variants of inborn errors of immunity in critically ill children admitted to the pediatric intensive care unit for sepsis: A Moroccan cohort study.La Tunisie medicale · 2025Article
- Article
- Tregopathy in focus.Frontiers in immunology · 2025Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 10 institutions in 2 countries.
Behdad AfzaliLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Juha GrönholmMolecular Development of the Immune System Section, NIAID Clinical Genomics Program, Biological Imaging Section (Research Technologies Branch) and Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Jana VandrovcovaMolecular Neuroscience, Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Charlotte O'BrienDepartment of Medicine, Imperial College London, London, UK.
Hong-Wei SunLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Ine VanderleydenLaboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge, UK.
Fred P DavisLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Ahmad KhoderDepartment of Medicine, Imperial College London, London, UK.
Yu ZhangMolecular Development of the Immune System Section, NIAID Clinical Genomics Program, Biological Imaging Section (Research Technologies Branch) and Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0002-6904-0372
Ahmed N HegazyTranslational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK.
Alejandro V VillarinoLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0001-8068-2176
Ira W PalmerLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Joshua KaufmanLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Norman R WattsLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Majid KazemianDepartment of Biochemistry and Department of Computer Science, Purdue University, West Lafayette, Indiana, USA.
Olena KamenyevaMolecular Development of the Immune System Section, NIAID Clinical Genomics Program, Biological Imaging Section (Research Technologies Branch) and Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Julia KeithTranslational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK.
Anwar SayedDepartment of Medicine, Imperial College London, London, UK.
Dalia KasperaviciuteImperial BRC Genomics Facility, Hammersmith Hospital, London, UK.
Michael MuellerImperial BRC Genomics Facility, Hammersmith Hospital, London, UK.
Jason D HughesMerck Research Laboratories, Merck &Co. Inc., Boston, Massachusetts, USA.
Ivan J FussMolecular Development of the Immune System Section, NIAID Clinical Genomics Program, Biological Imaging Section (Research Technologies Branch) and Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Mohammed F SadiyahLaboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge, UK.
Kim Montgomery-RechtClinical Research Directorate/CMRP, Leidos Biomedical Research Inc., NCI at Frederick, Frederick, Maryland, USA.
Joshua McElweeMerck Research Laboratories, Merck &Co. Inc., Boston, Massachusetts, USA.
Nicholas P RestifoNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Warren StroberMolecular Development of the Immune System Section, NIAID Clinical Genomics Program, Biological Imaging Section (Research Technologies Branch) and Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Michelle A LintermanLaboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge, UK.
Paul T WingfieldLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Holm H UhligTranslational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK.
Rahul RoychoudhuriLaboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge, UK.ORCID http://orcid.org/0000-0002-5392-1853
Timothy J AitmanDepartment of Medicine, Imperial College London, London, UK.
Peter KelleherDepartment of Medicine, Imperial College London, London, UK.
Michael J LenardoMolecular Development of the Immune System Section, NIAID Clinical Genomics Program, Biological Imaging Section (Research Technologies Branch) and Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
John J O'SheaLymphocyte Cell Biology Section (Molecular Immunology and Inflammation Branch), Biodata Mining and Discovery Section and Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Nichola CooperDepartment of Medicine, Imperial College London, London, UK.
Arian D J LaurenceTranslational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK.
National Institutes of Health · USImperial College London · GBBabraham Institute · GBJohn Radcliffe Hospital · GBHammersmith Hospital · GBMerck & Co., Inc., Rahway, NJ, USA (United States) · USLeidos (United States) · USNuffield Orthopaedic Centre · GBPurdue University West Lafayette · USUniversity College London · GB
Funding
Stat transcription factors in immunoregulation and autoimmune diseaseZIAAR041159 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2025
$49.3MAnimal care: supporting research on pathogenesis and treatment of autoimmunityZIGAR041168 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI WOO, JOSEPH · 2009 to 2025
$25.2MBuilding on the success of the adoptive immunotherapy of cancerZIABC010763 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2009 to 2020
$25.0MFlow cytometry support to research in immune, skin, muscle and bone diseasesZICAR041169 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI DELL'ORSO, STEFANIA · 2009 to 2025
$20.4MMolecular Mechanisms Of The Autoimmune Lymphoproliferative Syndrome And Other Immunoregulatory DisordersZIAAI000769 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN · 2009 to 2024
$16.7MHigh Throughput Next Generation Sequencing: supports genomics and epigenomics research in muscle, skin, bone and autoimmune diseases.ZICAR041207 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI DELL'ORSO, STEFANIA · 2016 to 2025
$12.3MGENE REGULATORY EVENTS IN ESTABLISHING MATURE T CELL TOLERANCEZIAAI000566 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2009 to 2025
$11.4MApplying Bioinformatics to Research in Immune, Muscle, and Bone DiseasesZIHAR041173 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI GADINA, MASSIMO · 2009 to 2020
$11.0MResource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2MCytokine Signaling and Primary ImmunodeficiencyZIAAR041167 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2019
$2.3MExpression, regulation, and role of enhancer RNAs in T helper cellsK22HL125593 · NHLBI · PURDUE UNIVERSITY · PI KAZEMIAN, MAJID · 2017 to 2019
$747kBiotechnology and Biological Sciences Research Council BB/N007794/1Biotechnology and Biological Sciences Research Council BBS/E/B/000C0407Biotechnology and Biological Sciences Research Council BBS/E/B/000C0409Cancer Research UK 22597CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z99 HL999999Medical Research Council MC_U120061454NCI NIH HHS HHSN261200800001ENHLBI NIH HHS K22 HL125593NIGMS NIH HHS P41 GM103311Wellcome Trust
Abstract
The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation. The mutations disrupted protein stability by interfering with homodimerization or by causing aggregation. We observed analogous lymphocyte defects in Bach2-heterozygous mice. More generally, we observed that genes that cause monogenic haploinsufficient diseases were substantially enriched for TFs and SE architecture. These findings reveal a previously unrecognized feature of SE architecture in Mendelian diseases of immunity: heterozygous mutations in SE-regulated genes identified by whole-exome/genome sequencing may have greater significance than previously recognized.
Indexed as
Adrenal Cortex HormonesAdultAutoimmune DiseasesBasic-Leucine Zipper Transcription FactorsColitisFemaleFeverHaploinsufficiencyHeterozygoteHumansImmunologic Deficiency SyndromesLymphopeniaMaleMiddle AgedMutationPancytopeniaAdrenal Cortex HormonesBACH2 protein, humanBasic-Leucine Zipper Transcription Factors
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
NCT00246857ClinicalTrials.gov
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.