While SLE is associated with more than 20 genes, AGS is caused by autosomal recessive mutations in one of several genes encoding enzymes involved in nucleic acid metabolism (TREX1, RNASEH2, ADAR and SAMHD1) or by gain-of-function mutations in the cytosolic RNA sensor IFIH12–7. Here, SAMHD1 is linked to systemic lupus erythematosus.