---
bibliography: 'morinlab.bib'
csl: 'NLM.csl'
link-citations: true
---
[[_TOC_]]

## Overview
Mutations in the DDX3X gene, which encodes an RNA helicase involved in various aspects of RNA metabolism, have significant implications in B-cell lymphomas, including BL, DLBCL, and other related malignancies and are particularly enriched within MYC-translocated tumors and those expressing the dark zone signature (DZsig).[@ennishiDoubleHitGeneExpression2019] 
These mutations are predominantly loss-of-function (LOF) mutations, affecting the helicase domain of the protein. Missense mutations are predominantly found in male patients and rarely in females, hence showing a sex-specific pattern.[@gongSequentialInverseDysregulation2021]


## Relevance tier by entity

|Entity|Tier|Description                           |
|:------:|:----:|--------------------------------------|
|![PMBL](images/icons/PMBL_tier1.png)|1|high-confidence PMBL/cHL/GZL gene[@mottokIntegrativeGenomicAnalysis2019]|
|![BL](images/icons/BL_tier1.png)    |1 | high-confidence BL gene               [@schmitzBurkittLymphomaPathogenesis2012]|
|![DLBCL](images/icons/DLBCL_tier1.png) |1 | high-confidence DLBCL gene            [@reddyGeneticFunctionalDrivers2017; @schmitzGeneticsPathogenesisDiffuse2018; @arthurGenomewideDiscoverySomatic2018]|
|![FL](images/icons/FL_tier2.png)    |2 | Although recurrent, the relevance of mutations in FL is tenuous |

## Mutation incidence in large patient cohorts (GAMBL reanalysis)

[[include:DLBCL_DDX3X.md]]
[[include:FL_DDX3X.md]]
[[include:BL_DDX3X.md]]

## Mutation pattern and selective pressure estimates

[[include:dnds_DDX3X.md]]

## aSHM regions

|chr_name|hg19_start|hg19_end|region                                                                                          |regulatory_comment|
|:--------:|:----------:|:--------:|:------------------------------------------------------------------------------------------------:|:------------------:|
|chrX    |42800580  |42804184|[intergenic](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chrX%3A42800580%2D42804184)|NA                |



[[include:browser_DDX3X.md]]

## Expression
![](images/gene_expression/DDX3X_by_pathology.svg)
<!-- ORIGIN: schmitzBurkittLymphomaPathogenesis2012 -->
<!-- DLBCL: schmitzGeneticsPathogenesisDiffuse2018a -->
<!-- BL: schmitzBurkittLymphomaPathogenesis2012 -->
<!-- BL: schmitzBurkittLymphomaPathogenesis2012 -->
<!-- PMBL: mottokIntegrativeGenomicAnalysis2019b -->

[[include:mermaid_DDX3X.md]]

## References