IRF4

interferon regulatory factor 4, the group of Interferon regulatory factors

Basic information

Region (hg38): 6:391738-411443

Previous symbols: [ "MUM1" ]

Links

ENSG00000137265 ∙ NCBI:3662 ∙ OMIM:601900 ∙ HGNC:6119 ∙ Uniprot:Q15306 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Skin/hair/eye pigmentation, variation in, 8	AD	General	Though potentially related to melanoma susceptibility, the clinical relevance of the condition is unclear	Dermatologic	17952075; 18483556; 19710684; 20602913; 24267888

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRF4 gene.

• not provided (204 variants)
• Inborn genetic diseases (10 variants)
• not specified (5 variants)
• IRF4-related condition (2 variants)
• SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRF4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	72	3	76
missense	1		80	2	3	86
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region			2	6	1	9
non coding			1	10	23	34
Total	1	0	87	84	29

Variants in IRF4

This is a list of pathogenic ClinVar variants found in the IRF4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-392783-G-A			Benign (Nov 12, 2018)
6-392866-A-G			Benign (Nov 12, 2018)
6-393154-T-G			Likely benign (Aug 17, 2023)
6-393158-C-T			Likely benign (May 20, 2021)
6-393159-C-T			Likely benign (Aug 03, 2023)
6-393166-G-A			Uncertain significance (Nov 10, 2023)
6-393168-G-C			Uncertain significance (May 26, 2023)
6-393172-G-A			Uncertain significance (Sep 07, 2022)
6-393175-G-A		not specified	Conflicting classifications of pathogenicity (Jan 25, 2024)
6-393175-G-T			Uncertain significance (Aug 15, 2022)
6-393179-C-T			Likely benign (Aug 04, 2023)
6-393188-C-G			Uncertain significance (Aug 21, 2022)
6-393191-C-T			Likely benign (Jan 11, 2024)
6-393193-T-C			Uncertain significance (Apr 18, 2022)
6-393205-G-A			Uncertain significance (Oct 06, 2023)
6-393205-G-C			Uncertain significance (Apr 03, 2023)
6-393218-G-A			Likely benign (Oct 05, 2023)
6-393225-C-G			Uncertain significance (Sep 29, 2021)
6-393227-C-T			Likely benign (Aug 17, 2023)
6-393238-T-G			Uncertain significance (Dec 24, 2020)
6-393243-C-G			Uncertain significance (Aug 23, 2022)
6-393264-C-T			Uncertain significance (Oct 30, 2023)
6-393272-G-A			Likely benign (Nov 22, 2023)
6-393281-G-A			Likely benign (Feb 24, 2023)
6-393284-CGAG-C			Uncertain significance (Jul 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRF4	protein_coding	protein_coding	ENST00000380956	8	19709

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.857	0.143	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.85	144	278	0.518	0.0000164	2960
Missense in Polyphen		33	101.58	0.32488		1106
Synonymous	0.309	115	119	0.964	0.00000813	845
Loss of Function	3.78	4	24.0	0.167	0.00000130	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000159	0.000156
Ashkenazi Jewish	0.00	0.00
East Asian	0.000587	0.000544
Finnish	0.0000468	0.0000462
European (Non-Finnish)	0.0000180	0.0000176
Middle Eastern	0.000587	0.000544
South Asian	0.0000368	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator. Binds to the interferon- stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and activation of genes (By similarity). {ECO:0000250|UniProtKB:Q64287}.
• Disease: DISEASE: Multiple myeloma (MM) [MIM:254500]: A malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. {ECO:0000269|PubMed:9326949}. Note=The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving IRF4 has been found in multiple myeloma. Translocation t(6;14)(p25;q32) with the IgH locus.
• Pathway: Th17 cell differentiation - Homo sapiens (human);White fat cell differentiation;B Cell Receptor Signaling Pathway;Apoptosis;Vitamin D Receptor Pathway;Preimplantation Embryo;Apoptotic Signaling Pathway;Development of pulmonary dendritic cells and macrophage subsets;Prion disease pathway;Interleukin-4 and 13 signaling;White fat cell differentiation;Type II interferon signaling (IFNG);T-Cell antigen Receptor (TCR) Signaling Pathway;the information processing pathway at the ifn beta enhancer;Cytokine Signaling in Immune system;Immune System;Interferon gamma signaling;Interferon alpha/beta signaling;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;Interferon Signaling;IL4-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.304

Intolerance Scores

• loftool: 0.136
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.91

Haploinsufficiency Scores

• pHI: 0.268
• hipred: Y
• hipred_score: 0.825
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Irf4
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; neoplasm; immune system phenotype

Zebrafish Information Network

• Gene name: irf4a
• Affected structure: thymus
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: peptidyl-lysine methylation;cytokine-mediated signaling pathway;negative regulation of toll-like receptor signaling pathway;T cell activation;defense response to protozoan;myeloid dendritic cell differentiation;positive regulation of DNA binding;histone H3 acetylation;histone H4 acetylation;positive regulation of interleukin-10 biosynthetic process;positive regulation of interleukin-2 biosynthetic process;positive regulation of interleukin-13 biosynthetic process;positive regulation of interleukin-4 biosynthetic process;regulation of T-helper cell differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;interferon-gamma-mediated signaling pathway;type I interferon signaling pathway;T-helper 17 cell lineage commitment;positive regulation of cold-induced thermogenesis
• Cellular component: nuclear nucleosome;nucleus;nucleoplasm;cytosol;membrane
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;transcription factor binding;protein-lysine N-methyltransferase activity;sequence-specific DNA binding