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. 2018 Jan 18;8:1978. doi: 10.3389/fimmu.2017.01978

Figure 2.

Figure 2

Mapping of human nuclear factor kappa-light-chain enhancer of activated B cells 1 (NF-κB1) mutations on the protein’s domain architecture. Comparison of identified NF-κB1 mutations and their clinical presentation reveals no obvious genotype–phenotype correlation. Individual mutations in either p105 or p105/p50 protein subunits of NF-κB1 are depicted by black bars. Stop codons are depicted by asterisks. NF-κB1 haploinsufficiency results from intronic mutations, non-sense mutations and frameshift mutations with premature truncations. Similarly, two identified splice-site mutations result in NF-κB1 haploinsufficiency due to loss of mutated precursors. Missense exchange p.I553M results in enhanced degradation of both p105 and p50, while p.H67R leads to reduced nuclear entry of the affected mutant p50 and, hence, to functional haploinsufficiency. NLS, nuclear localization sequence; RHD, Rel homology domain; GRR, glycine-rich region; DD, death domain. NF-κB1 mutations are referenced according to Roman numbering: (I) Kaustio et al. (9); (II) Schipp et al. (8); (III) Boztug et al. (7); (IV) Fliegauf et al. (5); (V) Lougaris, Moratto et al. (6); (VI) Maffucci et al. (10); (VII) Rae et al. (12); (VIII) Lougaris, Patrizi et al. (13) (IX) Keller et al. (11). Clinical presentations are indicated by the following symbols: #, common variable immunodeficiencies (CVID) (incl. autoimmunity); $, autoinflammation; §, chronic EBV/EBV-lymphoproliferation; ρ, combined immunodeficiency (CID).