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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IRF4
interferon regulatory factor 4
Chromosome 6 · 6p25.3
NCBI Gene: 3662Ensembl: ENSG00000137265.17HGNC: HGNC:6119UniProt: Q15306
256PubMed Papers
22Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusnucleoplasmcytoplasmmembranechronic lymphocytic leukemiamelanomamultiple myelomacutaneous melanoma
✦AI Summary

IRF4 (interferon regulatory factor 4) is a transcription factor that plays critical roles in immune cell development, function, and disease pathogenesis. IRF4 primarily functions as a transcriptional regulator by binding to interferon-stimulated response elements (ISRE) and immune-specific regulatory elements like AICE sequences, often in complex with other transcription factors such as BATF-JUNB 1. In B cell biology, IRF4 is essential for plasma cell differentiation and immunoglobulin production, requiring cooperation with the SWI/SNF chr6 remodeling complex member ARID1A 1. In T cells, IRF4 exhibits context-dependent functions: it promotes CD8+ T cell exhaustion during chr6 infections by upregulating inhibitory receptors like PD-1 and impairing effector functions 23, while also regulating T helper cell differentiation and cytokine production. Disease relevance includes mutations causing combined immunodeficiency, where a T95R variant creates multimorphic effects with altered DNA-binding specificity leading to profound immune dysfunction 4. In malignancies, IRF4 drives oncogenic programs in multiple myeloma through SWI/SNF-dependent mechanisms 15, and recurrent C99R mutations in lymphomas cause neomorphic DNA-binding activities that disrupt normal B cell identity 6. IRF4 also mediates inter-organ communication, as demonstrated in NASH pathogenesis through muscle-liver crosstalk via FSTL1 7.

Sources cited
1
IRF4 requires ARID1A for plasma cell identity and drives oncogenic programs in multiple myeloma through SWI/SNF-dependent mechanisms
PMID: 38906156
2
IRF4 promotes CD8+ T cell proliferation, PD-1 expression, and impairs effector functions
PMID: 38943641
3
IRF4 signaling in multiple myeloma depends on mSWI/SNF complex activity
PMID: 39029462
4
IRF4 T95R mutation causes autosomal dominant combined immunodeficiency through multimorphic effects on DNA binding
PMID: 36662884
5
IRF4 C99R mutation in lymphomas causes neomorphic DNA-binding activities that disrupt B cell identity
PMID: 37935654
6
IRF4 mediates muscle-liver crosstalk in NASH pathogenesis through transcriptional regulation of FSTL1
PMID: 37770480
7
IRF4 drives CD8+ T cell exhaustion during chronic infection by promoting inhibitory receptor expression and metabolic impairments
PMID: 29246443
Disease Associationsⓘ22
chronic lymphocytic leukemiaOpen Targets
0.63Moderate
melanomaOpen Targets
0.59Moderate
multiple myelomaOpen Targets
0.57Moderate
cutaneous melanomaOpen Targets
0.57Moderate
skin cancerOpen Targets
0.56Moderate
hair colorOpen Targets
0.56Moderate
skin diseaseOpen Targets
0.55Moderate
skin neoplasmOpen Targets
0.55Moderate
neoplasmOpen Targets
0.55Moderate
basal cell carcinomaOpen Targets
0.55Moderate
neurodegenerative diseaseOpen Targets
0.54Moderate
actinic keratosisOpen Targets
0.54Moderate
cancerOpen Targets
0.53Moderate
lymphoid leukemiaOpen Targets
0.53Moderate
hypothyroidismOpen Targets
0.52Moderate
androgenetic alopeciaOpen Targets
0.51Moderate
Abnormality of skin pigmentationOpen Targets
0.51Moderate
squamous cell carcinomaOpen Targets
0.51Moderate
benign neoplasm of eyeOpen Targets
0.51Moderate
sebaceous gland diseaseOpen Targets
0.50Moderate
Immunodeficiency 131UniProt
Multiple myelomaUniProt
Pathogenic Variants3
NM_002460.4(IRF4):c.1075T>C (p.Phe359Leu)Pathogenic
not provided|Immunodeficiency 131
★☆☆☆2023→ Residue 359
NM_002460.4(IRF4):c.284C>G (p.Thr95Arg)Pathogenic
not provided|Immunodeficiency 131
★☆☆☆2023→ Residue 95
NM_002460.4(IRF4):c.292C>T (p.Arg98Trp)Pathogenic
Immunodeficiency 131
☆☆☆☆2025→ Residue 98
View on ClinVar ↗
Related Genes
EP300Protein interaction100%SPI1Protein interaction100%JUNProtein interaction99%IFNGProtein interaction99%PTPRCProtein interaction98%FOXP3Protein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
12%
Liver
4%
Heart
2%
Ovary
2%
Brain
1%
Gene Interaction Network
Click a node to explore
IRF4EP300SPI1JUNIFNGPTPRCFOXP3
PROTEIN STRUCTURE
Preparing viewer…
PDB6TD4 · 1.71 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.38Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.23 [0.14–0.38]
RankingsWhere IRF4 stands among ~20K protein-coding genes
  • #1,500of 20,598
    Most Researched256 · top 10%
  • #3,921of 5,498
    Most Pathogenic Variants3
  • #1,855of 17,882
    Most Constrained (LOEUF)0.38 · top quartile
Genes detectedIRF4
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
IRF4 requires ARID1A to establish plasma cell identity in multiple myeloma.
PMID: 38906156
Cancer Cell · 2024
1.00
2
IRF4 impedes human CD8 T cell function and promotes cell proliferation and PD-1 expression.
PMID: 38943641
Cell Rep · 2024
0.90
3
Targeting the mSWI/SNF complex in POU2F-POU2AF transcription factor-driven malignancies.
PMID: 39029462
Cancer Cell · 2024
0.80
4
A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency.
PMID: 36662884
Sci Immunol · 2023
0.70
5
IRF4 expression by NK precursors predetermines exhaustion of NK cells during tumor metastasis.
PMID: 40524016
Nat Immunol · 2025
0.64