IRF8

interferon regulatory factor 8

9 disorders 8 untyped 1 causative 16q24.1 gene with protein product

HGNC:5358 Monarch NCBI Gene 3394 ENSG00000140968 UniProt Q02556 OMIM 601565

Previous symbols: ICSBP1. Aliases: IRF-8, ICSBP.

Normal function · from ai-gene-review (Q02556, commit 79fe13b38970) · AI-generated, not KB evidence

IRF8 (Interferon Regulatory Factor 8, also known as ICSBP) is a transcription factor of the IRF family that binds to interferon-stimulated response elements (ISRE), EICE (ETS-IRF composite elements with PU.1), and AICE (AP-1-IRF composite elements with BATF/JUN). It functions as both a transcriptional activator and repressor depending on context and binding partners. IRF8 is essential for myeloid and dendritic cell lineage specification, particularly for the development of plasmacytoid DCs (pDCs) and conventional DC1s (cDC1s). It regulates interferon and TLR signaling pathways and controls MHC class II antigen processing genes. Loss-of-function mutations cause immunodeficiency with dendritic cell and monocyte deficiency.

IRF8 is a sequence-specific DNA-binding transcription factor that binds ISRE, EICE, and AICE regulatory elements to control gene expression.

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific

IRF8 acts as a transcriptional repressor of interferon-inducible genes, maintaining submaximal activity that can be relieved by interferon treatment.

molecular function: DNA-binding transcription repressor activity, RNA polymerase II-specific · directly involved in: dendritic cell differentiation

IRF8 is essential for the development of conventional DC1 (cDC1) and plasmacytoid DC (pDC) populations. Human and mouse deficiency causes absence of these cell types.

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific · directly involved in: plasmacytoid dendritic cell differentiation

IRF8 is required for pDC development, the major producers of type I interferons.

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific · directly involved in: regulation of type I interferon production

IRF8 mediates cellular responses to IFN-gamma by translocating to the nucleus and regulating target gene expression.

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific · directly involved in: cellular response to type II interferon

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Mendelian Susceptibility To Mycobacterial Diseases Due To Partial IRF8 Deficiency	causative germline loss of function	mechanism: Heterozygous IRF8 T80A Impairs IRF8 DNA Binding
Ankylosing Spondylitis	untyped GWAS
Crohn Disease	untyped GWAS
Immunodeficiency 32B	untyped CAUSATIVE germline
Multiple Sclerosis	untyped GWAS
Psoriasis	untyped GWAS
Rheumatoid Arthritis	untyped GWAS
Systemic Lupus Erythematosus	untyped GWAS
Ulcerative Colitis	untyped GWAS

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.