Focusing on the potential pioneering activity of EBNA1, we were able to identify genes involved in purine metabolism, including AK4 and ADA. The importance of ADA in lymphocyte development is underscored by its frequent mutation in the most common form of severe combined immunodeficiency disease (SCID), and ADA deficiency is particularly detrimental to B-cells, including causing impaired germinal center maturation [59]. Here, ADA is linked to severe combined immunodeficiency.