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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\u2014including all heterozygous carriers\u2014was 78%, and the mean age of onset for the \u201cknown protein defect cohort\u201d 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 \u201caffected,\u201d but beyond this, the clinical manifestations did not differ between variant classes.<\/jats:p>","DOI":"10.70962\/jhi.20260076","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:28:37Z","timestamp":1792423717000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Genotype\u2013phenotype analysis in 333 individuals with heterozygous variants in\n                    <i>NFKB1<\/i>"],"prefix":"10.70962","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7544-5783","authenticated-orcid":true,"given":"Sophia Marie","family":"Armbruster","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03vzbgh69","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinic of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency, 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