IRF3: Interferon Regulatory Factor 3
Key transcription factor in innate immune response and antiviral signaling
Gene Information Card
| Symbol | IRF3 |
|---|---|
| Full Name | Interferon Regulatory Factor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 3661 ncbi.nlm.nih.gov/gene/3661 |
| Ensembl ID | ENSG00000126456 |
| UniProt ID | Q14653 |
| OMIM ID | 603734 |
| HGNC ID | 6118 |
| Aliases | IRF-3 |
Description
IRF3 (Interferon Regulatory Factor 3) encodes a member of the interferon regulatory transcription factor (IRF) family. The protein is a key component of the innate immune system, acting as a transcription factor that regulates the expression of type I interferons (e.g., IFN-β) and other cytokines in response to viral infection. IRF3 is activated by phosphorylation via TBK1 and IKKε following pattern recognition receptor (PRR) signaling, including TLR3, TLR4, RIG-I, and STING pathways. Upon activation, IRF3 dimerizes, translocates to the nucleus, and binds to interferon-stimulated response elements (ISRE) to induce target gene expression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| IRF3 deficiency (immunodeficiency) | Loss-of-function mutations impair type I interferon production, leading to increased susceptibility to viral infections | OMIM #603734; ClinVar |
| Herpes simplex encephalitis (HSE) | IRF3 mutations reduce antiviral response in the central nervous system, predisposing to severe HSV-1 encephalitis | PMID: 21983784; ClinVar |
| Systemic lupus erythematosus (SLE) | Dysregulated IRF3 activation contributes to aberrant type I interferon production and autoimmunity | PMID: 21217755; NCBI Gene |
| Viral myocarditis | IRF3-mediated interferon response influences cardiac inflammation and viral clearance | PMID: 23300459; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 14.2 | High |
| Spleen | 12.8 | High |
| Lung | 9.5 | Medium |
| Whole blood | 8.1 | Medium |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression in kidney epithelial cells |
| HeLa | 12.3 | Cervical cancer cell line |
| THP-1 | 18.7 | Monocytic leukemia cell line; high expression |
| Jurkat | 9.8 | T-cell leukemia cell line |
| HepG2 | 7.2 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; loss of function |
| c.286C>T (p.Arg96Trp) | Missense | Rare | Impaired DNA binding; loss of function |
| c.650G>A (p.Arg217Gln) | Missense | Rare | Reduced phosphorylation and activation |
| c.1120C>T (p.Arg374*) | Nonsense | Rare | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
IRF3 loss-of-function mutations impair type I interferon induction, increasing susceptibility to viral infections such as herpes simplex encephalitis.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in IRF3; constitutive activation is typically associated with upstream pathway dysregulation rather than IRF3 itself.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg96Trp) can act in a dominant-negative manner by forming inactive heterodimers with wild-type IRF3, reducing overall transcriptional activity.
View complete mutation data：
Gene Ontology (GO)
| • GO:0000978 ~ RNA polymerase II cis-regulatory region sequence-specific DNA binding | • GO:0001227 ~ DNA-binding transcription repressor activity |
| • RNA polymerase II-specific | • GO:0001228 ~ DNA-binding transcription activator activity |
| • RNA polymerase II-specific | • GO:0005515 ~ protein binding |
| • GO:0005634 ~ nucleus | • GO:0005737 ~ cytoplasm |
| • GO:0006355 ~ regulation of transcription | • DNA-templated |
| • GO:0006955 ~ immune response | • GO:0035458 ~ cellular response to interferon-beta |
| • GO:0045087 ~ innate immune response |
Pathways
• RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways (Reactome: R-HSA-168928)
• Toll-like Receptor 3 (TLR3) Cascade (Reactome: R-HSA-168164)
• STING pathway (Reactome: R-HSA-1834941)
• Cytosolic sensors of pathogen-associated DNA (Reactome: R-HSA-1834949)
• Interferon Signaling (Reactome: R-HSA-913531)
Protein Summary
IRF3 is a 427-amino acid protein (UniProt Q14653) containing an N-terminal DNA-binding domain (DBD) with a helix-turn-helix motif, a C-terminal IRF association domain (IAD) for dimerization, and a serine-rich region for phosphorylation. The protein is constitutively expressed in the cytoplasm. Upon viral infection, TBK1/IKKε phosphorylates IRF3 at Ser385, Ser386, Ser396, Ser398, Ser402, and Ser405, leading to homodimerization and nuclear translocation. In the nucleus, IRF3 binds to ISRE sequences to activate transcription of type I interferons and interferon-stimulated genes (ISGs). IRF3 also interacts with other transcription factors such as NF-κB and AP-1 to coordinate the innate immune response.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRF3 Knockout HEK293 Cell Line | EDJ-KQ960 | Human | 3661 | Details Get a Quote |
| IRF3 Knockout A-549 Cell Line | EDJ-KQ19954 | Human | 3661 | Details Get a Quote |
| IRF3 Knockout HeLa Cell Line | EDJ-KQ19955 | Human | 3661 | Details Get a Quote |
| IRF3 Knockout HCT 116 Cell Line | EDJ-KQ18631 | Human | 3661 | Details Get a Quote |
| Irf3 Knockout BHK-21 clone 13 Cell Line | EDC90486 | Golden hamster | 100765676 | Details Get a Quote |
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