Novel NFKB2 Pathogenic Variants in Two Unrelated Patients with Common Variable Immunodeficiency.

The conserved serine residues S866 and S870 are the major phosphorylation sites essential for the processing of p100 to p52 in cells. Keywords: Common Variable Immunodeficiency (CVID); NFKB2; novel pathogenic gene variants; lym1 mice; hypogammaglobulinaemia; autoimmunity EN Common Variable Immunodeficiency (CVID) NFKB2 novel pathogenic gene variants lym1 mice hypogammaglobulinaemia autoimmunity 1159 1164 6 07/20/23 20230801 NES 230801 Kruthika Sundaram and Micol Ferro contributed equally to this work. The reduction of p100 processing was linked to a markedly less increased phosphorylation of p100 in Patient 1 compared to the controls - which is likely caused by the absence of S870 in the p100 truncated form (p.Tyr868*). The two major phospho-serines (S866 & S870) create a binding site for -TrCP, the receptor subunit of the E3 ubiquitin ligase -TrCP SP SCF sp , which mediates p100 ubiquitination and its proteasomal-dependent processing to p52 employing the p100 ubiquitin acceptor site lysine 855 [[3]]. [Extracted from the article]