RFX5: A Master Regulator of MHC Class II Expression
Key transcription factor in immune response and bare lymphocyte syndrome
Gene Information Card
| Symbol | RFX5 |
|---|---|
| Full Name | Regulatory Factor X5 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 5993 ncbi.nlm.nih.gov/gene/5993 |
| Ensembl ID | ENSG00000143390 |
| UniProt ID | P48382 |
| OMIM ID | 601863 |
| HGNC ID | 9986 |
| Aliases | RFX5, regulatory factor X, 5 (influences HLA class II expression) |
Description
RFX5 encodes a transcription factor that is a critical component of the RFX complex, which binds to the X-box motif of MHC class II gene promoters. This protein is essential for the expression of MHC class II molecules on antigen-presenting cells, thereby playing a central role in the adaptive immune response. Mutations in RFX5 cause bare lymphocyte syndrome type II, complementation group C, a severe primary immunodeficiency characterized by a lack of MHC class II expression and recurrent infections.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bare lymphocyte syndrome type II (BLS II) | Loss-of-function mutations in RFX5 prevent formation of the RFX complex, abolishing MHC class II transcription. | ClinVar, OMIM |
| Severe combined immunodeficiency (SCID) | Impaired MHC class II expression leads to defective antigen presentation and T-cell deficiency. | OMIM |
| Autoimmune disorders (e.g., rheumatoid arthritis) | Polymorphisms in RFX5 may alter MHC class II expression levels, influencing autoimmune susceptibility. | NCBI Gene, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.5 | Medium |
| Lung | 6.2 | Low |
| Liver | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B-lymphocyte (GM12878) | 15.2 | High expression; consistent with role in MHC class II regulation |
| Monocyte (THP-1) | 11.7 | Moderate expression; inducible by IFN-gamma |
| HeLa | 7.4 | Low baseline expression |
| HEK293 | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.500C>T (p.Pro167Leu) | Missense | Rare | Loss of DNA-binding activity; associated with BLS II |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of protein; severe BLS II phenotype |
| c.1123delG (p.Glu375fs) | Frameshift | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported RFX5 mutations are loss-of-function, leading to absent or non-functional protein, resulting in bare lymphocyte syndrome type II.
Gain of Function (GOF)
No gain-of-function mutations have been described for RFX5.
Dominant Negative (DN)
No dominant-negative mutations have been reported; the disorder is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MHC class II antigen presentation (Reactome: R-HSA-2132295)
• Interferon-gamma signaling (Reactome: R-HSA-877300)
Protein Summary
RFX5 is a 616-amino-acid protein containing a DNA-binding domain and a dimerization domain. It forms a heterodimer with RFXAP and RFXANK to create the RFX complex, which binds the X-box of MHC class II promoters. This complex recruits other transcription factors (e.g., CIITA) to initiate transcription. Without functional RFX5, MHC class II expression is absent, leading to severe immunodeficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RFX5 Knockout HEK293 Cell Line | EDJ-KQ2104 | Human | 5993 | Details Get a Quote |
| RFX5 Knockout HeLa Cell Line | EDJ-KQ20929 | Human | 5993 | Details Get a Quote |
| RFX5 Knockout A-549 Cell Line | EDJ-KQ22222 | Human | 5993 | Details Get a Quote |
| RFX5 Knockout HCT 116 Cell Line | EDJ-KQ22223 | Human | 5993 | Details Get a Quote |
