IRF8 Gene: Interferon Regulatory Factor 8
A master regulator of immune cell development and myeloid differentiation, implicated in immunodeficiency and cancer.
Gene Information Card
| Symbol | IRF8 |
|---|---|
| Full Name | Interferon Regulatory Factor 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q24.1 |
| NCBI Gene ID | 3394 ncbi.nlm.nih.gov/gene/3394 |
| Ensembl ID | ENSG00000140968 |
| UniProt ID | Q02556 |
| OMIM ID | 601565 |
| HGNC ID | 6125 |
| Aliases | ICSBP, H-ICSBP, IRF-8 |
Description
IRF8 (Interferon Regulatory Factor 8) encodes a transcription factor that belongs to the interferon regulatory factor (IRF) family. It plays a critical role in the regulation of innate and adaptive immune responses, particularly in the development and function of myeloid cells, including macrophages, dendritic cells, and monocytes. IRF8 is involved in the transcriptional activation of genes responsive to interferon and is essential for the differentiation of common myeloid progenitors into specific lineages. Mutations in IRF8 are associated with immunodeficiency syndromes and susceptibility to infections, as well as with certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 32A (IMD32A) | Loss-of-function mutations in IRF8 impair myeloid cell differentiation, leading to severe monocytopenia and dendritic cell deficiency, causing susceptibility to infections. | OMIM #614893; ClinVar |
| Immunodeficiency 32B (IMD32B) | Autosomal dominant mutations in IRF8 (e.g., T80A) act in a dominant-negative manner, disrupting normal IRF8 function and causing selective depletion of CD1c+ dendritic cells and monocytes. | OMIM #614894; ClinVar |
| Chronic Myelogenous Leukemia (CML) | IRF8 expression is often downregulated in CML, contributing to the block in myeloid differentiation and promoting leukemogenesis. | COSMIC; PubMed studies |
| Acute Myeloid Leukemia (AML) | Reduced IRF8 expression or function is associated with poor differentiation and aggressive disease in some AML subtypes. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | High | High |
| Spleen | High | High |
| Bone Marrow | High | High |
| Lymph Node | High | High |
| Lung | Low | Low |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Monocytes | High | Key regulator of monocyte differentiation |
| Dendritic Cells | High | Essential for DC development |
| Macrophages | High | Regulates macrophage function |
| B Cells | Moderate | Involved in B cell development |
| T Cells | Low | Minimal expression |
| NK Cells | Low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| T80A | Missense | Rare | Dominant-negative effect; causes IMD32B |
| K108E | Missense | Rare | Loss-of-function; causes IMD32A |
| R294C | Missense | Rare | Loss-of-function; associated with susceptibility to mycobacterial infection |
| c.91C>T (p.R31X) | Nonsense | Rare | Loss-of-function; causes IMD32A |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., K108E, R294C) impair IRF8's DNA-binding or transactivation ability, leading to defective myeloid differentiation and immunodeficiency.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for IRF8; most pathogenic variants are loss-of-function or dominant-negative.
Dominant Negative (DN)
Dominant-negative mutations (e.g., T80A) interfere with wild-type IRF8 function, often by disrupting dimerization or DNA binding, leading to autosomal dominant immunodeficiency.
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 immune response |
| • myeloid cell differentiation | • response to interferon-gamma |
Pathways
• Interferon signaling
• Cytokine-cytokine receptor interaction
• Hematopoietic cell lineage
• Toll-like receptor signaling pathway
Protein Summary
IRF8 is a 424-amino acid protein with an N-terminal DNA-binding domain (DBD) containing a helix-turn-helix motif and a C-terminal IRF association domain (IAD) that mediates homo- and heterodimerization with other IRF family members. It functions as a transcription factor that binds to interferon-stimulated response elements (ISRE) and regulates gene expression. IRF8 is critical for the development of plasmacytoid dendritic cells and monocytes, and it modulates the balance between myeloid and lymphoid lineages. Its activity is regulated by post-translational modifications, including phosphorylation and ubiquitination.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRF8 Knockout HEK293 Cell Line | EDJ-KQ4957 | Human | 3394 | Details Get a Quote |
| IRF8 Knockout HeLa Cell Line | EDJ-KQ53603 | Human | 3394 | Details Get a Quote |
| IRF8 Knockout A-549 Cell Line | EDJ-KQ62072 | Human | 3394 | Details Get a Quote |
| IRF8 Knockout HCT 116 Cell Line | EDJ-KQ70554 | Human | 3394 | Details Get a Quote |
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