Taken together, our data indicated that PAX1 mutants found in SCID patients (Val147Leu, Asn155del, Gly166Val, Cys368*, c.1173-1174ins) significantly compromise its role in repressing canonical Wnt signaling pathway by perturbing its ability of modulating TCF7L2 SUMOylation. Here, PAX1 is linked to severe combined immunodeficiency.