NFKB1 and neoplasm: The tumor-associated OTUD4 H148Y missense variant (c.442C>T, p.H148Y), located within this loop, retains TAK1 binding but abolishes intrinsic deubiquitinase activity toward both K63- and K48-linked chains and is associated with sustained NF-κB activation and increased proinflammatory cytokine expression.