IRF4 Gene: Interferon Regulatory Factor 4
A master regulator of immune cell development and a key oncogene in hematological malignancies
Gene Information Card
| Symbol | IRF4 |
|---|---|
| Full Name | Interferon Regulatory Factor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p25.3 |
| NCBI Gene ID | 3662 ncbi.nlm.nih.gov/gene/3662 |
| Ensembl ID | ENSG00000137265 |
| UniProt ID | Q15306 |
| OMIM ID | 601900 |
| HGNC ID | 6116 |
| Aliases | MUM1, LSIRF, NF-EM5, SHEP8 |
Description
IRF4 (Interferon Regulatory Factor 4) is a transcription factor that belongs to the interferon regulatory factor (IRF) family. It plays a critical role in the regulation of immune responses, including the development and function of B and T lymphocytes, plasma cell differentiation, and immunoglobulin class switching. IRF4 is also involved in the regulation of apoptosis and cell cycle. Aberrant expression and mutations of IRF4 are associated with various hematological malignancies, including multiple myeloma, diffuse large B-cell lymphoma, and adult T-cell leukemia/lymphoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Multiple Myeloma | IRF4 is overexpressed due to chromosomal translocations (e.g., t(6;14)(p25;q32)) or copy number gains, driving oncogenic MYC expression and plasma cell proliferation. | COSMIC; ClinVar; PMID: 21796119 |
| Diffuse Large B-cell Lymphoma (DLBCL) | IRF4 translocations (e.g., t(6;14)) and mutations lead to constitutive activation, promoting B-cell survival and proliferation. | COSMIC; ClinVar; PMID: 23334667 |
| Adult T-cell Leukemia/Lymphoma (ATLL) | IRF4 is overexpressed in HTLV-1 infected cells, contributing to leukemogenesis by inhibiting apoptosis and promoting cell cycle progression. | COSMIC; PMID: 15536153 |
| Chronic Lymphocytic Leukemia (CLL) | IRF4 mutations (e.g., p.K59R) are recurrent, leading to altered transcriptional activity and B-cell receptor signaling. | ClinVar; PMID: 25426809 |
| Immunodeficiency (IRF4-related) | Biallelic loss-of-function mutations in IRF4 cause a primary immunodeficiency with combined B and T cell defects. | OMIM; PMID: 29263200 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Spleen | 55.2 | High |
| Lymph node | 48.7 | High |
| Bone marrow | 30.1 | Medium |
| Blood | 25.4 | Medium |
| Thymus | 20.3 | Medium |
| Lung | 5.2 | Low |
| Liver | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| RPMI-8226 (multiple myeloma) | 85.3 | High expression; IRF4 is essential for survival |
| U266 (multiple myeloma) | 78.9 | High expression; IRF4 drives MYC |
| SU-DHL-4 (DLBCL) | 65.2 | High expression; translocations present |
| Jurkat (T-cell leukemia) | 12.4 | Moderate expression |
| K562 (CML) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| p.K59R | Missense | ~5% in CLL | Alters DNA-binding affinity and transcriptional activity |
| p.R98W | Missense | Rare in DLBCL | Impairs IRF4 interaction with PU.1, reducing target gene activation |
| p.L116P | Missense | Rare in multiple myeloma | Disrupts protein stability and nuclear localization |
| t(6;14)(p25;q32) | Chromosomal translocation | ~15% in multiple myeloma | Places IRF4 under immunoglobulin heavy chain enhancer, causing overexpression |
| Copy number gain (6p25) | Copy number alteration | ~20% in multiple myeloma | Increases IRF4 gene dosage and expression |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., frameshift, nonsense) cause immunodeficiency with impaired B and T cell function, as reported in OMIM and ClinVar.
Gain of Function (GOF)
Chromosomal translocations and copy number gains leading to IRF4 overexpression are considered gain-of-function events, driving oncogenic transcription programs in multiple myeloma and DLBCL.
Dominant Negative (DN)
Some missense mutations (e.g., p.R98W) may act in a dominant-negative manner by interfering with wild-type IRF4's interaction with partner factors like PU.1, as suggested by functional studies.
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 |
| • B cell differentiation | • Plasma cell differentiation |
| • Regulation of cell population proliferation | • Apoptotic process |
| • Response to interferon-gamma |
Pathways
• B cell receptor signaling pathway
• Plasma cell differentiation
• Interferon signaling pathway
• MYC transcriptional activation
• Toll-like receptor signaling pathway
Protein Summary
The IRF4 protein is a 451-amino acid transcription factor with an N-terminal DNA-binding domain containing a helix-turn-helix motif and a C-terminal IRF association domain (IAD) that mediates interactions with other transcription factors such as PU.1 and SPIB. IRF4 binds to interferon-stimulated response elements (ISRE) and ETS/IRF composite elements (EICE) to regulate gene expression. It is essential for the maturation of B cells into plasma cells and for the function of regulatory T cells. In cancer, IRF4 acts as a lineage-survival oncogene, particularly in multiple myeloma, where it is required for tumor cell survival and proliferation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRF4 Knockout HEK293 Cell Line | EDJ-KQ3195 | Human | 3662 | Details Get a Quote |
| IRF4 Knockout HeLa Cell Line | EDJ-KQ77865 | Human | 3662 | Details Get a Quote |
| IRF4 Knockout A-549 Cell Line | EDJ-KQ77866 | Human | 3662 | Details Get a Quote |
| IRF4 Knockout HCT 116 Cell Line | EDJ-KQ77867 | Human | 3662 | Details Get a Quote |
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