Overactivation of the PI3K pathway leads to phosphoinositide 3–kinase d syndrome (APDS), a type of immunodeficiency disease with major clinical symptoms including recurrent sinus infection, conjunctivitis, bacterial lymphadenitis and herpes virus infection, and benign lymphocyte proliferation, malignant tumors and autoimmune manifestations. Here, PIK3CD is linked to immunodeficiency disease.