NFKB2 Gene D81.4

The NFKB2 gene (NFKB2-stands for Nuclear Factor Kappa B Subunit 2) is a protein-coding gene located on chromosome 10q24.32. There is a pseudogene for this gene on chromosome 18. Alternative splicing results in multiple transcript variants.

Diseases associated with NFKB2 include immunodeficiency, common variable, 10(immunodeficiency 10 and NLKB2 defect; CVID10).

Chromosomal rearrangements and translocations of this locus have been observed in B-cell lymphomas.

NF-kappa-B complexes are maintained in an inactive state in the cytoplasm and are complexed with members of the NF-kappa-B inhibitor family (I-kappa-B). In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to various activators and subsequently degraded, releasing the active NF-kappa-B complex that migrates to the nucleus.

In a non-canonical activation pathway, the CHUK/IKKA homodimer activated by MAP3K14 phosphorylates NFKB2/p100 associated with RelB, triggering its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B-RelB-p52 complexes

1. Aird A et al (2019) Novel heterozygous mutation in NFKB2 is associated with early onset CVID and a functional defect in NK cells complicated by disseminated CMV infection and severe nephrotic syndrome. Front Pediat 7: 303.
2. Brue T et al (2014) Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies. BMC Med Genet 15: 139.
3. Chen K et al (2013) Germline mutations in NFKB2 implicate the noncanonical NF-kappa-B pathway in the pathogenesis of common variable immunodeficiency. Am J Hum Genet 93: 812-824.
4. Lee CE et al (2014) Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood 124: 2964-2972.
5. Liu Y et al (2014) Novel NFKB2 mutation in early-onset CVID J Clin Immun 34: 686-690.
6. Quentien MH et al (2012) Deficit in anterior pituitary function and variable immune deficiency (DAVID) in children presenting with adrenocorticotropin deficiency and severe infections. J Clin Endocr Metab 97: E121-E128.
7. Tucker E et al (2007) A novel mutation in the Nfkb2 gene generates an NF-kappa-B2 'super repressor. J Immun 179: 7514-7522.