IRF4 interferon regulatory factor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IRF4provided by HGNC
Official Full Name: interferon regulatory factor 4provided by HGNC
Primary source: HGNC:HGNC:6119
See related: Ensembl:ENSG00000137265 MIM:601900; AllianceGenome:HGNC:6119
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MUM1; LSIRF; SHEP8; NF-EM5
Summary: The protein encoded by this gene belongs to the IRF (interferon regulatory factor) family of transcription factors, characterized by an unique tryptophan pentad repeat DNA-binding domain. The IRFs are important in the regulation of interferons in response to infection by virus, and in the regulation of interferon-inducible genes. This family member is lymphocyte specific and negatively regulates Toll-like-receptor (TLR) signaling that is central to the activation of innate and adaptive immune systems. A chromosomal translocation involving this gene and the IgH locus, t(6;14)(p25;q32), may be a cause of multiple myeloma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2010]
Expression: Broad expression in lymph node (RPKM 13.5), bone marrow (RPKM 12.6) and 14 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p25.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (391752..411443)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (250136..269771)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (391752..411443)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clinical boundaries in adult cases of large B cell lymphoma with IRF4 rearrangement.
Title: Clinical boundaries in adult cases of large B cell lymphoma with IRF4 rearrangement.
Transcriptional reprogramming by mutated IRF4 in lymphoma.
Title: Transcriptional reprogramming by mutated IRF4 in lymphoma.
Molecular basis for the functional roles of the multimorphic T95R mutation of IRF4 causing human autosomal dominant combined immunodeficiency.
Title: Molecular basis for the functional roles of the multimorphic T95R mutation of IRF4 causing human autosomal dominant combined immunodeficiency.
Human inborn errors of immunity associated with IRF4.
Title: Human inborn errors of immunity associated with IRF4.
NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis.
Title: NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis.
Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.
Title: Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.
MUM-1 in canine lymphoma: A pilot study.
Title: MUM-1 in canine lymphoma: A pilot study.
Prevalence of IRF4 rearrangement in large B-cell lymphomas of the Waldeyer's ring in adults.
Title: Prevalence of IRF4 rearrangement in large B-cell lymphomas of the Waldeyer's ring in adults.
A neomorphic mutation in the interferon activation domain of IRF4 causes a dominant primary immunodeficiency.
Title: A neomorphic mutation in the interferon activation domain of IRF4 causes a dominant primary immunodeficiency.
IRF4 as a novel target involved in malignant transformation of oral submucous fibrosis into oral squamous cell carcinoma.
Title: IRF4 as a novel target involved in malignant transformation of oral submucous fibrosis into oral squamous cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (200)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Skin/hair/eye pigmentation, variation in, 8 MedGen: C2673265 OMIM: 611724 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic determinants of hair, eye and skin pigmentation in Europeans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of serum albumin:globulin ratio in Korean populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed
Web-based, participant-driven studies yield novel genetic associations for common traits. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-N33454 (e-PCR)
- UniSTS:29327

RH104416 (e-PCR)
- UniSTS:98741

SHGC-106840 (e-PCR)
- UniSTS:184295

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription coactivator activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in T cell activation	NAS Non-traceable Author Statement more info	PubMed
involved_in T-helper 17 cell lineage commitment	ISS Inferred from Sequence or Structural Similarity more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in defense response to protozoan	ISS Inferred from Sequence or Structural Similarity more info
involved_in immune system process	IBA Inferred from Biological aspect of Ancestor more info
involved_in myeloid dendritic cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of toll-like receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of interleukin-10 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-13 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-2 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-4 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of T-helper cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of chromatin	ISA Inferred from Sequence Alignment more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
part_of nucleosome	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IC Inferred by Curator more info	PubMed

General protein information

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Preferred Names: interferon regulatory factor 4

Names: lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027728.1 RefSeqGene

Range

5014..24705

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001195286.2 → NP_001182215.1 interferon regulatory factor 4 isoform 2

See identical proteins and their annotated locations for NP_001182215.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame acceptor splice site at an internal coding exon compared to variant 1, resulting in an isoform (2) that is 1 aa shorter than isoform 1.

Source sequence(s)

AL512308, AL589962, AW197089, BG230623, BM551611, KF458069, U52682, U63738

Consensus CDS

CCDS93847.1

UniProtKB/TrEMBL

F2Z3D5

Related

ENSP00000512940.1, ENST00000696871.1

Conserved Domains (2) summary

pfam00605
Location:23 → 128

IRF; Interferon regulatory factor transcription factor

pfam10401
Location:249 → 417

IRF-3; Interferon-regulatory factor 3
NM_002460.4 → NP_002451.2 interferon regulatory factor 4 isoform 1

See identical proteins and their annotated locations for NP_002451.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AL512308, AL589962, AW197089, BC015752, BG230623, BM551611, KF458069, U52682, U63738

Consensus CDS

CCDS4469.1

UniProtKB/Swiss-Prot

Q15306, Q5VUI7, Q99660

UniProtKB/TrEMBL

F2Z3D5

Related

ENSP00000370343.4, ENST00000380956.9

Conserved Domains (2) summary

pfam00605
Location:23 → 128

IRF; Interferon regulatory factor transcription factor

pfam10401
Location:250 → 418

IRF-3; Interferon-regulatory factor 3

RNA

NR_046000.3 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate 3' splice pattern, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AL512308, AL589962, AW197089, D78261, KF458069, U52682

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

391752..411443

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006715090.3 → XP_006715153.1 interferon regulatory factor 4 isoform X1

See identical proteins and their annotated locations for XP_006715153.1

UniProtKB/TrEMBL

F2Z3D5

Conserved Domains (2) summary

pfam00605
Location:23 → 128

IRF; Interferon regulatory factor transcription factor

pfam10401
Location:214 → 382

IRF-3; Interferon-regulatory factor 3
XM_047418730.1 → XP_047274686.1 interferon regulatory factor 4 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

250136..269771

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054355349.1 → XP_054211324.1 interferon regulatory factor 4 isoform X1
XM_054355350.1 → XP_054211325.1 interferon regulatory factor 4 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NR_036585.1: Suppressed sequence

Description

NR_036585.1: This RefSeq was permanently suppressed because currently there is support for the transcript.