Novel monogenic diseases causing human autoimmunity

•PRKCD autosomal recessive mutations cause an ALPS-like disease and SLE.•Dominant CTLA4 loss of function mutations cause immunodeficiency and autoimmunity.•Dominant STAT3 gain of function mutations cause autoimmunity and ALPS-like disease.•IFIH1 and TMEM173 gain of function mutations cause type I interferonopathies.•COPA heterozygous mutations cause inflammatory lung disease with autoantibodies.

Fuelled by the on-going sequencing revolution, the last two years have seen a number of exciting discoveries relating to monogenic disorders predisposing to autoimmunity that provide new insights into the function of the human immune system. Here we discuss a selection of these diseases due to mutations in PRKCD, CTLA4, STAT3, IFIH1, TMEM173 and COPA.