IRF5 Gene: Interferon Regulatory Factor 5 - Function, Disease Associations, and Expression
A master regulator of innate immunity and inflammation, implicated in autoimmune diseases and cancer.
Gene Information Card
| Symbol | IRF5 |
|---|---|
| Full Name | Interferon Regulatory Factor 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q32.1 |
| NCBI Gene ID | 3663 ncbi.nlm.nih.gov/gene/3663 |
| Ensembl ID | ENSG00000128604 |
| UniProt ID | Q13568 |
| OMIM ID | 607218 |
| HGNC ID | 6120 |
| Aliases | SLEB10; IRF-5 |
Description
IRF5 encodes interferon regulatory factor 5, a transcription factor that plays a critical role in the innate immune response. It is activated by Toll-like receptors (TLRs) and RIG-I-like receptors, leading to the induction of type I interferons and pro-inflammatory cytokines. IRF5 is involved in the regulation of apoptosis, cell cycle, and immune cell differentiation. Genetic variants of IRF5 are strongly associated with susceptibility to systemic lupus erythematosus (SLE), rheumatoid arthritis, and other autoimmune diseases. Additionally, IRF5 has been implicated in cancer progression and prognosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic Lupus Erythematosus (SLE) | Risk haplotypes increase IRF5 expression and interferon production, driving autoimmunity. | Strong association in multiple GWAS and functional studies (PMID: 15619631, 17554342). |
| Rheumatoid Arthritis (RA) | IRF5 variants contribute to inflammatory cytokine production and disease susceptibility. | Meta-analyses confirm association (PMID: 19865098). |
| Inflammatory Bowel Disease (IBD) | IRF5 modulates intestinal inflammation via type I IFN and cytokine responses. | Genetic association and functional studies (PMID: 21102463). |
| Cancer (e.g., breast, gastric) | IRF5 acts as a tumor suppressor or promoter depending on context; regulates apoptosis and immune evasion. | Expression and functional studies (PMID: 19029902, 22108914). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.3 | Medium |
| Lymph Node | 10.8 | Medium |
| Bone Marrow | 8.5 | Low |
| Lung | 6.2 | Low |
| Liver | 4.1 | Low |
| Brain | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression; responsive to TLR stimulation. |
| K-562 (leukemia) | 8.7 | Moderate expression. |
| HeLa (cervical) | 3.4 | Low expression. |
| A549 (lung) | 2.1 | Low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2004640 (intronic) | SNP | ~30% (G allele) | Creates a splice site, increasing IRF5 expression and risk for SLE. |
| rs10954213 (3'UTR) | SNP | ~40% (A allele) | Affects mRNA stability, leading to higher IRF5 levels and autoimmunity risk. |
| rs3807306 (promoter) | SNP | ~35% (T allele) | Alters promoter activity, influencing IRF5 transcription. |
| Coding mutations (e.g., p.Gln166Arg) | Missense | Rare | Functional impact unclear; may affect DNA binding or protein stability. |
Mutation functional classification
Loss of Function (LOF)
Rare loss-of-function mutations may impair IRF5-mediated cytokine production, leading to immunodeficiency or altered immune responses.
Gain of Function (GOF)
Common risk variants (e.g., rs2004640, rs10954213) increase IRF5 expression, resulting in enhanced type I IFN and inflammatory cytokine production, contributing to autoimmunity.
Dominant Negative (DN)
Some IRF5 isoforms (e.g., IRF5-3) act as dominant-negative inhibitors, reducing transcriptional activity and modulating immune responses.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • Protein dimerization activity | • Regulation of type I interferon production |
| • Innate immune response | • Cytokine-mediated signaling pathway |
| • Apoptotic process | • Cellular response to lipopolysaccharide |
Pathways
• Toll-like receptor signaling pathway
• RIG-I-like receptor signaling pathway
• Cytosolic DNA-sensing pathway
• Interferon signaling pathway
• Cytokine-cytokine receptor interaction
Protein Summary
IRF5 is a 504-amino acid protein with an N-terminal DNA-binding domain (DBD) and a C-terminal IRF association domain (IAD). It forms homo- or heterodimers with other IRF family members. Upon TLR activation, IRF5 is phosphorylated by TBK1/IKKε, leading to nuclear translocation and transcriptional activation of target genes such as IFNA, IFNB, IL6, and TNF. IRF5 also interacts with MYD88 and TRAF6 in the TLR signaling cascade. Its expression is tightly regulated at transcriptional and post-translational levels, and dysregulation is linked to autoimmune and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRF5 Knockout HEK293 Cell Line | EDJ-KQ3840 | Human | 3663 | Details Get a Quote |
| IRF5 Knockout A-549 Cell Line | EDJ-KQ25999 | Human | 3663 | Details Get a Quote |
| IRF5 Knockout HCT 116 Cell Line | EDJ-KQ26000 | Human | 3663 | Details Get a Quote |
| IRF5 Knockout HeLa Cell Line | EDJ-KQ53671 | Human | 3663 | Details Get a Quote |
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