Disease relevance of RFXAP

• Mutations in RFXAP are the genetic basis for complementation group D cases of the bare lymphocyte syndrome (BLS) immunodeficiency [1].

High impact information on RFXAP

• Its interaction with RFX5 and RFXAP is essential for binding of the RFX complex to MHC-II promoters [2].
• A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients [2].
• METHODS: To elucidate the genetic defect in patients with MHC class II deficiency that was not classified genetically, we performed direct complementation assays with the three genes known to regulate the expression of MHC class II genes, CIITA, RFX5, and RFXAP, and the relevant mutations were identified in each patient [3].
• Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiency [3].
• Transfection with the wild-type RFXAP gene restored the expression of MHC class II molecules in the patients' cells [3].

Biological context of RFXAP

• Complementation of the 6.1.6 and DA cell lines by transfection with RFXAP fully restores expression of all endogenous MHC-II genes in vivo, demonstrating that RFXAP is a novel essential MHC-II regulatory gene [4].
• Additionally, a nuclear export signal was identified in the N terminus of RFXAP [5].
• Moreover, mutation of potential phosphorylation sites abolished RFXAP activity [1].
• The ability of RFXAP mutants to rescue one isotype, but not another was investigated by their ability to form RFX complexes, bind DNA in vivo, recruit CIITA to promoters and to activate a series of chimeric reporter genes [1].

Anatomical context of RFXAP

• RFXAP is mutated in the 6.1.6 cell line (group D), as well as in an MHC-II deficiency patient (DA) [4].

Associations of RFXAP with chemical compounds

• In this study, we demonstrate that RFXANK(B) binds to RFXAP to form a scaffold for the assembly of the RFX complex, which then binds to DNA [6].

Physical interactions of RFXAP

• The region of the RFXAP protein that binds BRG1 coincides with the minimally required fragment of RFXAP previously reported to be necessary to mediate MHC class II gene transcription [7].

Other interactions of RFXAP

• RFX5 and RFXAP are two subunits of RFX, a multi-protein complex that binds the X box motif of MHC-II promoters [2].
• Molecular analysis confirmed the presence of homozygous mutations in the RFXANK and RFXAP genes, respectively [8].
• The C-terminal third of RFXAP, which contained an extensive glutamine-rich tract, could rescue HLA-DR, but not HLA-DQ or HLA-DP expression in a BLS cell line [1].

References