Year: 2026
Type: article
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.
Source: Journal of Human Immunity
Authors: Sophia Marie Armbruster, Andres Caballero-Oteyza, Oliver Bartsch, Tiziana Lorenzini, Hassan Abolhassani, Samantha Chan, Luis Ignacio González Granado, Victor Garcia-Bustos, Marta Dafne Cabañero Navalon, Nazanin Fathi, Nima Rezaei, Mathieu Fusaro, Roger Colobran, Kaan Boztug, Michele Proietti, Bodo Grimbacher
Institutions: University of Freiburg, University Medical Center Freiburg, University Medical Center of the Johannes Gutenberg University Mainz, University Children's Hospital Zurich, Karolinska Institutet, The Royal Melbourne Hospital, Research Institute Hospital 12 de Octubre, Hospital Universitario 12 De Octubre, Hospital Universitari i Politècnic La Fe, Instituto de Investigación Sanitaria La Fe, Children's Medical Center, Tehran University of Medical Sciences, Centre National de la Recherche Scientifique, Université Toulouse III - Paul Sabatier, Inserm, Centre Hospitalier Universitaire de Toulouse, Institut Toulousain des Maladies Infectieuses et Inflammatoires, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, University of Bonn, Austrian Academy of Sciences, University Hospital Bonn, CeMM Research Center for Molecular Medicine, St. Anna Children's Cancer Research Institute, Medical University of Vienna, German Center for Infection Research
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
Awards: G1078610655, G259924242, G3523822304, G4206229305, EXC 2155: RESIST Resolving Infection Susceptibility, EXC 2189: CIBSS Centre for Integrative Biological Signalling Studies, G5186833673, G6351858858, Estudio del genoma completo y priorización de variantes por términos HPO en pacientes con inmunodeficiencias primarias sin diagnóstico molecular, G7833425038
OpenAlex ID: W7222927767