Oftedal and colleagues identified heterozygous, dominantly acting AIRE missense variants clustering in the PHD1 zinc-finger domain, associated with later onset, milder autoimmunity and reduced penetrance (“non-classical” APS-1), whereas most recessive missense variants in classical APS-1 map to the N-terminal CARD/HSR region; thus, whether an AIRE allele behaves recessively or dominantly is strongly influenced by its position and the domain it perturbs [37]. This evidence concerns the gene AIRE and Autoimmunity.