Scheme of RAG1 protein and mutations. WT human RAG1 consists of 1043 amino acids and includes an N-terminus domain, really interesting new gene (RING) finger sequence, zinc finger sequences zinc finger A (ZFA) and zinc finger B (ZFB), the catalytic core, which contains the nonamer- and heptamer-binding regions, and a C-terminus domain. The amino acid positions affected by mutations identified in patients with SCID (P1 and P2) and with OS (P3), and the respective consequences on amino acid sequence are shown. P1 and P2 were homozygous for a frameshift (N476Kfs*16) and a missense (R394W) mutation, respectively. P3 was compound heterozygous for a missense (E722K) and a frameshift (K86Vfs*33). For the latter, an alternative start codon can be used resulting in an N-terminus truncated protein with normal sequence from Met183 onward with cytoplasmic localization. HBR, heptamer-binding region; NBR, nonamer-binding region.