Furthermore, Btk has been reported to regulate osteoclast differentiation by RANK and ITAM signals, which congenital defect can cause an arrest in B cell development and immunodeficiency (31).This indicated that it might lead to insufficient RANK signal which in turn leads to a decrease in the differentiation of osteoclasts or osteoblasts. The gene discussed is TNFRSF11A; the disease is immunodeficiency disease.