RFXANK Human
Description
Gene Structure and Protein Composition
The RFXANK gene is located on chromosome 19p13.11 and encodes a 260-amino-acid protein containing four ankyrin repeats, which mediate protein-protein interactions .
Functional Role in MHC Class II Gene Regulation
RFXANK forms a heterotrimeric complex with RFX5 and RFXAP, binding to X box motifs in MHC II promoters. This complex recruits CIITA (class II transactivator) to activate transcription .
Key Interactions
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RFX5 and RFXAP: Core components of the RFX complex, stabilizing DNA binding .
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CIITA: Essential for cell-type-specific and inducible MHC II expression .
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Caspase-2: Identified interaction suggests potential roles in apoptosis or transcriptional regulation .
Clinical Implications: Bare Lymphocyte Syndrome (BLS) Type II
Mutations in RFXANK are the most common cause of BLS type II, characterized by impaired MHC II expression and severe immunodeficiency .
Emerging Neurological Phenotypes
Recent studies reveal RFXANK mutations may contribute to progressive ataxia and neurodegeneration .
Key Findings
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RFXANK Expression in Brain: Detected in basal ganglia, hippocampus, and cerebellum .
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Case Reports:
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Proposed Mechanism: MHC II-independent roles in brain development or neuronal maintenance .
Genetic Mutations and Functional Impact
Over 40 RFXANK mutations have been identified, primarily causing loss-of-function (LOF) or splicing defects .
| Mutation | Effect | Source |
|---|---|---|
| c.337+1G>C | Splicing defect → nonfunctional protein | |
| W188X (c.563G>A) | Premature stop codon → truncated protein | |
| 26-bp Deletion | Founder mutation in North African populations |
Research Frontiers and Therapeutic Insights
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Caspase-2 Interaction: Potential link to apoptosis or transcriptional modulation .
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BMT and Neuroprotection: Early BMT may mitigate neurological regression by restoring RFXANK function .
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Gene Editing: Exploratory approaches to correct RFXANK mutations in hematopoietic cells .
Expression Patterns and Tissue Distribution
RFXANK is expressed in immune cells (lymphocytes, dendritic cells) and neural tissues .
| Tissue | Expression Level | Function | Source |
|---|---|---|---|
| Immune Cells | High | MHC II gene regulation | |
| Brain | Moderate | Brain development/maintenance |
Diagnostic and Prognostic Biomarkers
Product Specs
Product Science Overview
Regulatory Factor X-Associated Ankyrin-Containing Protein (RFXANK) is a crucial component in the regulation of major histocompatibility complex (MHC) class II gene expression. This protein is encoded by the RFXANK gene and plays a significant role in the immune system by influencing the transcription of MHC class II molecules, which are essential for the immune response.
The RFXANK gene is located on chromosome 19 in humans . The protein encoded by this gene contains three ankyrin repeats, which are known for their role in protein-protein interactions . These ankyrin repeats are essential for the formation of the regulatory factor X (RFX) complex, which is necessary for binding to the X box motif of MHC class II gene promoters .
RFXANK, along with regulatory factor X-associated protein (RFXAP) and regulatory factor-5 (RFX5), forms the RFX complex . This complex binds to the X box motif of certain MHC class II gene promoters and activates their transcription . The activation of these promoters is crucial for the expression of MHC class II molecules, which present antigens to T cells and initiate an immune response .
Once the RFX complex binds to the promoter, it associates with the non-DNA-binding factor MHC class II transactivator (CIITA), which controls the cell type specificity and inducibility of MHC class II gene expression . This interaction ensures that MHC class II molecules are expressed in the appropriate cells and under the right conditions.
Mutations in the RFXANK gene have been linked to bare lymphocyte syndrome type II, complementation group B . This rare genetic disorder is characterized by a lack of MHC class II expression, leading to severe immunodeficiency. Patients with this condition are highly susceptible to infections due to the impaired ability of their immune system to present antigens and activate T cells .
Human recombinant RFXANK is produced using recombinant DNA technology, which involves inserting the RFXANK gene into a suitable expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant protein can be used for various research purposes, including studying the function of RFXANK in the immune system and developing potential therapies for conditions related to MHC class II deficiency.
