Mutations in all of these regions have severe effects on the normal function of Orai1 (e.g., Orai1 E106Q blocks Ca2+ permeation [101], Orai1 V102A impairs selectivity that can be rescued by STIM1 binding [96,102], and Orai1 R91W is one of the best-known loss-of-function (LoF) mutations leading to severe combined immune deficiency [66,103]). The gene discussed is ORAI1; the disease is Immunodeficiency.