RFXAP

At least seven mutations in the RFXAP gene have been found to cause an immune system disorder called bare lymphocyte syndrome type II (BLS II). BLS II is a type of combined immunodeficiency (CID), in which affected individuals have virtually no immune protection from foreign invaders. Consequently, individuals with BLS II have persistent infections in the respiratory, gastrointestinal, and urinary tracts, which can be life-threatening.

Mutations in the RFXAP gene lead to production of an abnormally short RFXAP protein that likely does not function properly, if any protein is produced at all. These changes impair binding of the RFX complex to DNA, which prevents transcription of MHC class II proteins. Consequently, lymphocytes lack any MHC class II proteins on their surface, and the body has difficulty getting rid of bacteria, viruses, and fungi, leading to the persistent infections characteristic of BLS II.

At least one mutation in the RFXAP gene has been found to cause bare lymphocyte syndrome type III (BLS III). This type of bare lymphocyte syndrome is characterized by absence of MHC class II proteins and a reduced amount of MHC class I proteins on the surface of lymphocytes. However, it is unclear if BLS III is a distinct diagnosis. Some doctors consider such cases to be BLS II (described above). Both types of BLS cause persistent, life-threatening infections.

The RFXAP gene mutation involved in BLS III likely impairs the function of the RFX complex, preventing transcription of MHC class II genes and reducing the activity of MHC class I genes. Without the important immune system proteins produced from these genes, the body is less able to fight infections. It is unclear why certain RFXAP gene mutations impair production of MHC class I proteins and others do not.