--- bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true --- [[_TOC_]] ## 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](https://github.com/morinlab/LLMPP/wiki/ashm) 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. ## Relevance tier by entity |Entity|Tier|Description | |:------:|:----:|--------------------------| |![PMBL](images/icons/PMBL_tier2.png)|2|relevance in PMBL/cHL/GZL not firmly established[@mottokIntegrativeGenomicAnalysis2019]| |![DLBCL](images/icons/DLBCL_tier1.png) |1 | aSHM target and high-confidence DLBCL gene[@morinFrequentMutationHistonemodifying2011]| |![FL](images/icons/FL_tier1.png) |1 | aSHM target and high-confidence FL gene | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) [[include:DLBCL_IRF4.md]] [[include:FL_IRF4.md]] ## Mutation pattern and selective pressure estimates [[include:dnds_IRF4.md]] ## aSHM regions |chr_name|hg19_start|hg19_end|region |regulatory_comment| |:--------:|:----------:|:--------:|:-------------------------------------------------------------------------------------:|:------------------:| |chr6 |390572 |394093 |[TSS](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chr6%3A390572%2D394093)|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 | [[include:browser_IRF4.md]] ## Expression ![](images/gene_expression/IRF4_by_pathology.svg) [[include:mermaid_IRF4.md]] ## References