IRF9 Gene: Interferon Regulatory Factor 9
Key mediator of type I interferon signaling and antiviral immunity
Gene Information Card
| Symbol | IRF9 |
|---|---|
| Full Name | Interferon Regulatory Factor 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q12 |
| NCBI Gene ID | 10379 ncbi.nlm.nih.gov/gene/10379 |
| Ensembl ID | ENSG00000113916 |
| UniProt ID | Q00978 |
| OMIM ID | 147574 |
| HGNC ID | 6131 |
| Aliases | ISGF3G, p48, IRF-9 |
Description
IRF9 (Interferon Regulatory Factor 9) encodes a transcription factor that is a critical component of the ISGF3 complex, which mediates type I interferon (IFN-alpha/beta) signaling. Upon IFN stimulation, IRF9 forms a complex with STAT1 and STAT2, translocates to the nucleus, and binds to interferon-stimulated response elements (ISREs) to induce expression of interferon-stimulated genes (ISGs) that establish antiviral, antibacterial, and immunomodulatory states. IRF9 also participates in type III interferon signaling and has been implicated in cell growth regulation and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 65 (IMD65) | Loss-of-function mutations in IRF9 impair ISGF3 complex formation, leading to defective type I and III interferon responses and increased susceptibility to severe viral infections, particularly influenza. | ClinVar, OMIM (147574) |
| Susceptibility to viral infections (e.g., influenza, SARS-CoV-2) | IRF9 deficiency disrupts ISG induction, compromising antiviral immunity. | ClinVar, PubMed (PMID: 30054296) |
| Systemic lupus erythematosus (SLE) (association) | Altered IRF9 expression may affect interferon signaling, contributing to autoimmune pathogenesis. | PubMed (PMID: 23396208) |
| Cancer (various) | Dysregulation of IRF9 expression can modulate interferon responses, affecting tumor surveillance and progression. | COSMIC, PubMed (PMID: 26921328) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.6 | Medium |
| Spleen | 11.8 | Medium |
| Bone marrow | 10.9 | Medium |
| Lung | 9.8 | Low |
| Liver | 8.7 | Low |
| Brain | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical carcinoma; high expression |
| K-562 | 12.1 | Chronic myeloid leukemia; moderate |
| A549 | 10.4 | Lung carcinoma; moderate |
| MCF7 | 8.9 | Breast adenocarcinoma; low |
| HepG2 | 7.6 | Hepatocellular carcinoma; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.991C>T (p.Arg331*) | Nonsense | Rare (found in IMD65) | Premature stop codon; loss of IRF9 protein function |
| c.1240G>A (p.Glu414Lys) | Missense | Rare (found in IMD65) | Disrupts DNA binding or protein interactions |
| c.1129C>T (p.Arg377Trp) | Missense | Rare (found in IMD65) | Impairs ISGF3 complex formation |
| c.1486delA (p.Thr496Profs*13) | Frameshift | Rare (found in IMD65) | Loss of function due to truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most IRF9 mutations reported in IMD65 are loss-of-function, leading to impaired ISGF3 complex formation and defective ISG induction.
Gain of Function (GOF)
No gain-of-function mutations have been clinically characterized; IRF9 is not typically associated with oncogenic activation.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming nonfunctional complexes with STAT1/STAT2, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein heterodimerization activity | • protein homodimerization activity |
| • transcription cis-regulatory region binding | • nucleus |
| • cytoplasm | • ISGF3 complex |
| • regulation of transcription by RNA polymerase II | • type I interferon signaling pathway |
| • type III interferon signaling pathway | • response to virus |
| • innate immune response | • positive regulation of transcription by RNA polymerase II |
| • negative regulation of viral genome replication |
Pathways
• RIG-I-like receptor signaling pathway
• Cytosolic DNA-sensing pathway
• Toll-like receptor signaling pathway
• Hepatitis C and hepatitis B pathways
• Influenza A pathway
• Measles pathway
• Herpes simplex infection pathway
• JAK-STAT signaling pathway
• Interferon alpha/beta signaling
• Interferon gamma signaling
Protein Summary
IRF9 is a 393-amino acid protein (UniProt Q00978) that contains a conserved N-terminal DNA-binding domain (DBD) with a helix-turn-helix motif and a C-terminal IRF association domain (IAD) that mediates interactions with STAT1 and STAT2. It is primarily cytoplasmic in unstimulated cells and translocates to the nucleus upon IFN stimulation. IRF9 lacks intrinsic transcriptional activation domains but functions as a key adaptor that stabilizes the ISGF3 complex and directs sequence-specific DNA binding to ISREs. Post-translational modifications, including phosphorylation and ubiquitination, regulate its stability and activity. IRF9 also interacts with other transcription factors and chromatin modifiers to modulate gene expression beyond canonical ISGs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRF9 Knockout HEK293 Cell Line | EDJ-KQ504 | Human | 10379 | Details Get a Quote |
| IRF9 Knockout HeLa Cell Line | EDJ-KQ18010 | Human | 10379 | Details Get a Quote |
| IRF9 Knockout A-549 Cell Line | EDJ-KQ18819 | Human | 10379 | Details Get a Quote |
| IRF9 Knockout HCT 116 Cell Line | EDJ-KQ18820 | Human | 10379 | Details Get a Quote |
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