Patients with mutations in ORAI1, STIM1, CD3γ and IκBα (yellow symbols) have impaired T cell activation and but normal numbers of lymphocytes. By contrast, SCID patients with mutations in other signaling molecules (red symbols) show severe defects in the development of T cells or T cell subsets [2]. Abbreviations: DAG, diacylglycerol; InsP3, inositol-1,4,5-trisphosphate; LAT, linker for activation of T cells; NFAT, nuclear factor of activated T cells; PLC, phospholipase; PtdIns(4,5)P2, phosphatidylinositol-4,5-bisphosphate; SLP76, SH2-domain-containing leukocyte protein of 76 kDa; STIM1, stromal interaction molecule 1; ZAP-70, ζ-chain-associated protein kinase of 70 kDa.