Table of Contents

Overview

Mutations in IL4R have been identified in various types of B-cell lymphomas, particularly primary mediastinal large B-cell lymphoma (PMBCL) and DLBCL. IL4R 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. IL4R mutations are found in approximately 24.2% of primary PMBCL cases. These mutations are commonly single nucleotide variants in exon 8, resulting in the I242N amino acid change. This leads to constitutive activation of the JAK-STAT signaling pathway and upregulation of downstream cytokine expression profiles and B cell-specific antigens.1,2 In DLBCL, IL4R mutations are more rare and tend to occur within the GCB subgroup.2

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a gain of function (GOF).1

Relevance tier by entity

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Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 30 0.0275 [0.0178,0.0373]
DLBCL GAMBL with Reddy 2,088 55 0.0263 [0.0195,0.0332]
DLBCL BC 231 4 0.0173 [5e-04,0.0341]
DLBCL Dana-Farber 303 12 0.0396 [0.0176,0.0616]
DLBCL NCI 470 10 0.0213 [0.0082,0.0343]
DLBCL Reddy 999 25 0.0250 [0.0153,0.0347]
DLBCL DLBCL_ICGC 85 4 0.0471 [0.002,0.0921]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 4.1865 0.0000 1.0000
FL 2.6221 0.0000 1.0000
DLBCL 3.7060 2.4852 0.0045

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr16 27322895 27329423 TSS active_promoter

IL4R Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr16 27367183 T>A I242N

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Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2018-05-03 : Vigan : PMBL 2021-07-15 : Duns : DLBCL

References

1.
Viganò E, Gunawardana J, Mottok A, Van Tol T, Mak K, Chan FC, Chong L, Chavez E, Woolcock B, Takata K, Twa D, Shulha HP, Telenius A, Kutovaya O, Hung SS, Healy S, Ben-Neriah S, Leroy K, Gaulard P, Diepstra A, Kridel R, Savage KJ, Rimsza L, Gascoyne R, Steidl C. Somatic IL4R mutations in primary mediastinal large B-cell lymphoma lead to constitutive JAK-STAT signaling activation. Blood. 2018 May 3;131(18):2036–2046.
2.
Duns G, Viganò E, Ennishi D, Sarkozy C, Hung SS, Chavez E, Takata K, Rushton C, Jiang A, Ben-Neriah S, Woolcock BW, Slack GW, Hsi ED, Craig JW, Hilton LK, Shah SP, Farinha P, Mottok A, Gascoyne RD, Morin RD, Savage KJ, Scott DW, Steidl C. Characterization of DLBCL with a PMBL gene expression signature. Blood. 2021 Jul 15;138(2):136–148.

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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