{ "abstract": "Heterozygous germline variants in NFKB1 can be classified into variants with \"known protein defect\" and \"unknown protein effect.\" However, beyond this, NFKB1 variants may be additionally categorized into at least eight distinct variant classes. We conducted a literature review of 67 papers reporting on NFKB1 variants and included four additional individuals, carrying previously unreported NFKB1 variants. We identified 333 individuals with unique variants in NFKB1. Our compiled data revealed that there is no sex predilection, the penetrance-including all heterozygous carriers-was 78%, and the mean age of onset for the \"known protein defect cohort\" was 21.2 years. Individuals harboring variants with a known protein defect demonstrated a higher frequency of malignancies and autoimmune disorders. However, these individuals were less frequently classified as affected than individuals with variants with unknown protein defect. Carriers of whole NFKB1 gene deletions had a significantly higher penetrance to being designated as \"affected,\" but beyond this, the clinical manifestations did not differ between variant classes.", "abstract_shown": true, "affiliations": [ "Faculty of Medicine, Clinic of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency, Medical Center, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.", "Faculty of Medicine, Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.", "RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg , Freiburg, Germany.", "Department of Human Genetics, Medical Care Center, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.", "Division of Immunology and Children's Research Center, University Children's Hospital Zürich, Zürich, Switzerland.", "Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.", "Department of Clinical Immunology & Allergy, Royal Melbourne Hospital, Melbourne, Australia.", "Primary Immunodeficiencies Unit, Department of Pediatrics, Hospital 12 Octubre, Research Institute University Hospital 12 de Octubre Complutense School of Medicine, Madrid, Spain.", "Primary Immunodeficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe, Valencia, Spain.", "Severe Infection Research Group, Health Research Institute La Fe , Valencia, Spain.", "Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe , Valencia, Spain.", "Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran.", "Immunology Department Laboratory, Referral Medical Biology Laboratory, Toulouse University Hospital Center, Toulouse, France.", "INFINITY - Toulouse Institute for Infectious and Inflammatory Diseases, INSERM, U1291, CNRS U5051, University Toulouse III , Toulouse, France.", "Translational Immunology Research Group, Immunology Division, Department of Cell Biology, Physiology and Immunology, Vall D'Hebron Research Institute, Vall D'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.", "Clinic for Pediatric Immunology and Rheumatology, University of Bonn, University Hospital Bonn , Bonn, Germany.", "St. Anna Children's Cancer Research Institute , Vienna, Austria.", "Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.", "CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , Vienna, Austria.", "German Center for Infection Research, Satellite Center Freiburg , Freiburg, Germany.", "Centre for Integrative Biological Signaling Studies, Albert-Ludwigs University , Freiburg, Germany." ], "article_type": "research article", "arxiv": null, "author_total": 16, "authors": [ { "affs": [ 0, 1 ], "name": "Sophia Marie Armbruster", "orcid": "0009-0007-7544-5783" }, { "affs": [ 1, 2 ], "name": "Andres Caballero-Oteyza", "orcid": "0000-0002-8892-1255" }, { "affs": [ 3 ], "name": "Oliver Bartsch", "orcid": "0000-0001-6329-696X" }, { "affs": [ 4 ], "name": "Tiziana Lorenzini", "orcid": "0009-0008-9457-2419" }, { "affs": [ 5 ], "name": "Hassan Abolhassani", "orcid": "0000-0002-4838-0407" }, { "affs": [ 6 ], "name": "Samantha Chan", "orcid": "0000-0002-3785-7759" }, { "affs": [ 7 ], "name": "Luis Ignacio González Granado", "orcid": "0000-0001-6917-8980" }, { "affs": [ 8, 9 ], "name": "Victor Garcia-Bustos", "orcid": "0000-0002-1785-258X" }, { "affs": [ 8, 10 ], "name": "Marta Dafne Cabañero Navalon", "orcid": "0000-0002-1447-9214" }, { "affs": [ 11 ], "name": "Nazanin Fathi", "orcid": "0000-0002-9562-9623" }, { "affs": [ 11 ], "name": "Nima Rezaei", "orcid": "0000-0002-3836-1827" }, { "affs": [ 12, 13 ], "name": "Mathieu Fusaro", "orcid": "0000-0002-5332-3626" }, { "affs": [ 14 ], "name": "Roger Colobran", "orcid": "0000-0002-5964-536X" }, { "affs": [ 15, 16, 17, 18 ], "name": "Kaan Boztug", "orcid": "0000-0001-8387-9185" }, { "affs": [ 1, 2 ], "name": "Michele Proietti", "orcid": "0000-0003-3095-0886" }, { "affs": [ 0, 1, 19, 20, 2 ], "name": "Bodo Grimbacher", "orcid": "0000-0002-6897-6806" } ], "bibtex": "https://research.draconitic.com/paper/43r4kjzx2f8hn.bib", "cited_by": 0, "doi": "10.70962/jhi.20260076", "fulltext_url": "https://europepmc.org/articles/PMC13679715", "id": "43r4kjzx2f8hn", "issns": [ "3065-8993" ], "landing_url": "https://europepmc.org/article/MED/42895832", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2403|Immunodeficiency and Autoimmune Disorders" ] ], "openalex": "W7222927767", "pdf_url": "https://europepmc.org/articles/PMC13679715?pdf=render", "pmcid": "PMC13679715", "pmid": "42895832", "published": "2026-10-19", "publisher": null, "ris": "https://research.draconitic.com/paper/43r4kjzx2f8hn.ris", "sources": [ { "first_seen": "2026-10-30T12:19:32Z", "native_id": "MED:42895832", "source": "europepmc", "url": "https://europepmc.org/article/MED/42895832" } ], "subjects": [ { "field": "biology", "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders", "subfield": "immunology" } ], "title": "Genotype-phenotype analysis in 333 individuals with heterozygous variants in NFKB1.", "title_text": "Genotype-phenotype analysis in 333 individuals with heterozygous variants in NFKB1.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:19:32Z", "url": "https://research.draconitic.com/paper/43r4kjzx2f8hn", "venue": "Journal of human immunity", "versions": [] }