IRF4 - morinlab/LLMPP GitHub Wiki
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IRF4
Overview
IRF4 (Interferon Regulatory Factor 4) encodes a transcription factor that plays a critical role in the regulation of immune response genes and B-cell development. Mutations and rearrangements in the IRF4 gene have been implicated in various B-cell lymphomas, including DLBCL. IRF4-rearranged large B-cell lymphomas (LBCL-IRF4) show a unique molecular profile with strong expression of IRF4/MUM1 and are associated with favorable outcomes. MUM1 staining is also commonly used to assign DLBCLs to one of the two cell-of-origin (COO) subgroups by immunohistochemistry. IRF4 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. There are a few mutation hotspots in this gene. The functional role of mutations in IRF4 in the absence of a rearrangement remains poorly understood.
History
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timeline
title Publication timing
2011-07-27 : Morin : DLBCL
2019-09-05 : Mottok : PMBL
Relevance tier by entity
| Entity | Tier | Description |
|---|---|---|
 |
2 | relevance in PMBL/cHL/GZL not firmly established[@mottokIntegrativeGenomicAnalysis2019b] |
 |
1-a | aSHM target and high-confidence DLBCL gene[@morinFrequentMutationHistonemodifying2011] |
 |
1-a | aSHM target and high-confidence FL gene |
Mutation incidence in large patient cohorts (GAMBL reanalysis)
| Entity | source | frequency (%) |
|---|---|---|
| DLBCL | GAMBL genomes | 4.40 |
| DLBCL | Schmitz cohort | 7.02 |
| DLBCL | Reddy cohort | 4.40 |
| DLBCL | Chapuy cohort | 2.14 |
| FL | GAMBL genomes | 1.15 |
Mutation pattern and selective pressure estimates
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | Yes | No | 0.000 | 0 |
| DLBCL | Yes | Yes | 25.817 | 0 |
| FL | Yes | No | 0.000 | 0 |
aSHM regions
| chr_name | hg19_start | hg19_end | region | regulatory_comment |
|---|---|---|---|---|
| chr6 | 390572 | 394093 | TSS | active_promoter |
IRF4 Hotspots
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr6 | 393328 | A>G | K59R |
| chr6 | 393340 | A>G | N63S |
| chr6 | 393360 | C>G | L70V |
| chr6 | 393360 | C>T | L70F |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
IRF4 Expression
