Table of Contents

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).1 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.2

Experimental Evidence

Driver mutations affecting this gene in DLBCL/BL have been experimentally demonstrated to cause a reduction or loss of function (LOF).2

Relevance tier by entity

Entity Tier Description
BL 1 High-confidence BL gene
DLBCL 1 High-confidence DLBCL gene
FL 2 Role of DDX3X mutations in FL requires confirmation
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 59 0.0542 [0.0407,0.0676]
DLBCL GAMBL with Reddy 2,088 104 0.0498 [0.0405,0.0591]
DLBCL BC 231 17 0.0736 [0.0399,0.1073]
DLBCL Dana-Farber 303 15 0.0495 [0.0251,0.0739]
DLBCL NCI 470 22 0.0468 [0.0277,0.0659]
DLBCL Reddy 999 45 0.0450 [0.0322,0.0579]
DLBCL DLBCL_ICGC 85 5 0.0588 [0.0088,0.1088]

FL

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BL

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Mutation pattern and selective pressure estimates

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aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chrX 42800580 42804184 intergenic NA
Structure with HotMAPS hotspots

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Expression

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References

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Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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