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RFXAP
regulatory factor X associated protein
The RFXAP gene provides instructions for making the RFX associated protein, which is vital for the proper function of the immune system. The RFXAP gene is responsible for producing a protein called RFXAP, a component of the regulatory factor X (RFX) complex.
RFXAP is located on the long (q) arm of chromosome 13, at band 13q13.3. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The RFXAP gene encodes the regulatory factor X associated protein, RFXAP, which is a key component of the RFX transcription factor complex. This complex helps regulate the expression of major histocompatibility complex (MHC) class II genes. Proper functioning of MHC class II proteins is fundamental for the immune system to recognise and respond to foreign invaders such as bacteria and viruses.
Mutations in the RFXAP gene can impair the production of MHC class II proteins, leading to immunodeficiency conditions like bare lymphocyte syndrome type II (BLS II). This condition significantly reduces an individual's ability to fight infections.
What the gene does
The RFXAP protein is integral to the regulatory factor X (RFX) complex, a group of proteins that primarily control the transcription of major histocompatibility complex (MHC) class II genes. Transcription is the initial step in producing proteins, and RFXAP ensures the RFX complex can correctly attach to specific DNA regions that regulate MHC class II gene activity. By facilitating this attachment, RFXAP helps to activate the transcription of these genes, leading to the production of MHC class II proteins.
MHC class II proteins are found on the surface of various immune cells, including lymphocytes, and are crucial for the body's adaptive immune response. They bind to protein fragments (peptides) from pathogens and present them to other immune cells, triggering an immune response to eliminate foreign invaders. The RFX complex also contributes to MHC class I gene transcription, though its role here is less prominent than for MHC class II genes.
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Chromosome location
The RFXAP gene is located on chromosome 13 at position 13q13.3. This chromosomal location indicates where the gene resides within the human genome, influencing its expression and potential involvement in genetic conditions.
Protein structure
The RFXAP protein is composed of 272 amino acids. Its structural organisation includes several regions, with a Disordered region found near the N-terminus (amino acids 1-20) and another Disordered region between amino acids 74-142. A crucial Nuclear localization signal is situated from amino acids 163-178, which is likely involved in directing the protein to the cell nucleus. Further downstream, another Disordered region spans amino acids 175-195. The C-terminal domain, located from amino acids 214-270, completes the protein structure.
Key variants
Variants within the RFXAP gene can lead to changes in the RFXAP protein, potentially affecting its ability to support MHC class II gene transcription. These genetic alterations can range from single nucleotide changes to larger deletions or insertions, and their impact varies depending on the specific change and its location within the gene.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in the RFXAP gene are primarily associated with bare lymphocyte syndrome type II (BLS II), a severe immune disorder. This condition is characterised by a significant deficiency in MHC class II proteins, leading to a compromised immune system and increased susceptibility to persistent infections affecting the respiratory, gastrointestinal, and urinary tracts. Some cases initially described as bare lymphocyte syndrome type III (BLS III) are now often considered to fall under the spectrum of BLS II.
No disease links recorded for this gene in our reference set.
UK clinical status
The RFXAP gene is included in several NHS England Genomic Medicine Service national genomic test directories. It has a green RAG (Red, Amber, Green) rating for 'COVID-19 research' and 'Primary immunodeficiency or monogenic inflammatory bowel disease (R15)', indicating its relevance for these specific clinical areas within the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the RFXAP gene?
The RFXAP gene provides instructions for making a protein that is part of the RFX complex, which is crucial for controlling the activity of MHC class II genes. These genes are essential for the proper functioning of the immune system.
What condition is associated with RFXAP gene variants?
Variants in the RFXAP gene are primarily associated with bare lymphocyte syndrome type II (BLS II). This is a severe immunodeficiency characterised by a lack of MHC class II proteins, leading to recurrent infections.
How does the RFXAP protein contribute to immunity?
The RFXAP protein helps the RFX complex bind to DNA, enabling the transcription of MHC class II genes. The resulting MHC class II proteins display foreign peptides to immune cells, initiating an immune response against pathogens.
References
- Gokturk B, Artac H, van Eggermond MJ. Type III bare lymphocyte syndrome associated with a novel RFXAP mutation: a case report. International journal of immunogenetics. 2012. PMID: 22390233
- Briggs L, Laird K, Boss JM. Formation of the RFX gene regulatory complex induces folding of the interaction domain of RFXAP. Proteins. 2009. PMID: 19274739
- Garvie CW, Boss JM. Assembly of the RFX complex on the MHCII promoter: role of RFXAP and RFXB in relieving autoinhibition of RFX5. Biochimica et biophysica acta. 2008. PMID: 18723135
- Burd AL, Ingraham RH, Goldrick SE. Assembly of major histocompatibility complex (MHC) class II transcription factors: association and promoter recognition of RFX proteins. Biochemistry. 2004. PMID: 15461447
- Gobin SJ, Peijnenburg A, van Eggermond M. The RFX complex is crucial for the constitutive and CIITA-mediated transactivation of MHC class I and beta2-microglobulin genes. Immunity. 1998. PMID: 9806639
- Villard J, Lisowska-Grospierre B, van den Elsen P. Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiency. The New England journal of medicine. 1997. PMID: 9287230