ORAI1 and immunodeficiency disease: Recessive, loss-of-function mutations in STIM1 or ORAI1 result in reduced protein expression or disrupted STIM1-ORAI1 coupling, thus leading to insufficient SOCE and severe combined immunodeficiency (Feske et al, 2006; Lacruz and Feske, 2015; Picard et al, 2009).