Recent discoveries have now moved beyond relatively simple LOF mutations, and there is now an interesting spectrum of additional clinical phenotypes attributed to CARD11 mutations (25), with gain-of-function mutations causing “B cell Expansion with NF-κB and T cell Anergy” (BENTA) disease (26–30), hypomorphic dominant-interfering mutations causing combined immunodeficiency with atopic disease “CARD11-associated Atopy with Dominant Interference of NF-κB Signaling” (CADINS) (31, 32), and loss-of-function mutations with somatic reversion associated with Omenn syndrome (19) (Figure 1). Here, NFKB1 is linked to immunodeficiency disease.