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RFXANK
regulatory factor X associated ankyrin containing protein
The RFXANK gene provides instructions for a protein critical to immune system function, primarily by regulating major histocompatibility complex (MHC) class II genes. The RFXANK gene plays a vital role in the adaptive immune system.
RFXANK is located on the short (p) arm of chromosome 19, at band 19p13.11. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The RFXANK gene, also known as regulatory factor X associated ankyrin containing protein, is fundamental for the proper functioning of the immune system. It directs the production of a protein that is an integral component of the RFX complex. This complex is responsible for regulating the expression of major histocompatibility complex (MHC) class II genes, which are essential for the body's ability to recognise and fight infections.
What the gene does
The protein encoded by the RFXANK gene is a key part of the regulatory factor X (RFX) complex. This complex attaches to specific DNA regions, enabling the transcription of MHC class II genes, which are vital for generating MHC class II proteins. These proteins are located on the surface of various immune cells, such as lymphocytes, where they present fragments of foreign invaders to other immune cells, initiating an immune response against pathogens like bacteria, viruses, and fungi. While the RFX complex also influences MHC class I gene activity, its primary regulatory role is with MHC class II genes. The RFXANK protein specifically assists the complex in binding to the correct DNA sequences, facilitating the recruitment of other necessary proteins to turn on MHC class II gene transcription.
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Chromosome location
The RFXANK gene is located on chromosome 19, specifically at position 19p13.11. This genomic location specifies where the gene can be found within the human genome.
Protein structure
The RFXANK protein consists of 260 amino acids. Its structure includes several key domains. An N-terminal Disordered region spans amino acids 1-79. Following this, there are five Ankyrin (ANK) repeats: ANK 1 from amino acids 89-118, ANK 2 from 123-152, ANK 3 from 156-185, ANK 4 from 189-218, and ANK 5 from 222-251. These ANK repeats are known to mediate protein-protein interactions.
Key variants
Genetic changes, or variants, in the RFXANK gene can affect the function of the encoded protein, leading to impaired immune responses. Over 40 different mutations have been identified within this gene, influencing its ability to properly regulate immune-related genes. The clinical impact of these variants can differ, ranging from significant immune deficiencies to milder effects depending on the specific change.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Mutations in the RFXANK gene are the most frequent genetic cause of bare lymphocyte syndrome type II (BLS II), a severe immune disorder. Individuals with BLS II have a significantly compromised immune system, making them highly susceptible to various infections. This condition is categorised as a combined immunodeficiency due to the lack of effective immune protection against foreign invaders.
No disease links recorded for this gene in our reference set.
UK clinical status
The RFXANK gene is included in UK diagnostic testing panels, as indicated by its presence in NHS England's Genomic Medicine Service pathways. It is currently part of the COVID-19 research panel and the Primary immunodeficiency or monogenic inflammatory bowel disease panel, both of which are classified as 'green' in PanelApp, signifying that there is sufficient evidence for its use in routine clinical diagnostic testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the RFXANK gene?
The RFXANK gene is crucial for immune system function, as it encodes a protein that helps regulate the activity of major histocompatibility complex (MHC) class II genes, which are essential for recognising and fighting infections.
What condition is most commonly associated with RFXANK gene variants?
Variants in the RFXANK gene are most frequently linked to bare lymphocyte syndrome type II (BLS II), a severe immune disorder characterised by a significant lack of immune protection.
How does the RFXANK gene contribute to immunity?
The RFXANK protein, as part of the RFX complex, enables the transcription of MHC class II genes. The resulting MHC class II proteins display foreign fragments to immune cells, initiating an immune response against pathogens.
References
- 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
- Masternak K, Barras E, Zufferey M. A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients. Nature genetics. 1998. PMID: 9806546
- 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