Table of Contents

Overview

NFKBIE encodes IκBε, a negative regulator of NF-κB. Mutations in NFKBIE can disrupt this regulatory function, leading to constitutive activation of NF-κB signaling.1 Mutations are relatively common in DLBCL and MCL.2

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).3

Relevance tier by entity

Entity Tier Description
DLBCL 1 High-confidence DLBCL gene
MCL 1 High-confidence MCL gene
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

MCL

pathology Collection N mutated Incidence CI
MCL GAMBL 160 6 0.0347 [0.0064,0.0631]
MCL BC_MCL 103 3 0.0291 [0,0.0616]
MCL Barcelona 57 3 0.0526 [0,0.1106]

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 45 0.0413 [0.0295,0.0531]
DLBCL GAMBL with Reddy 2,088 74 0.0354 [0.0275,0.0434]
DLBCL BC 231 4 0.0173 [5e-04,0.0341]
DLBCL Dana-Farber 303 9 0.0297 [0.0106,0.0488]
DLBCL NCI 470 27 0.0574 [0.0364,0.0785]
DLBCL Reddy 999 29 0.0290 [0.0186,0.0394]
DLBCL DLBCL_ICGC 85 5 0.0588 [0.0088,0.1088]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 2.0193 0.0000 1.0000
FL 0.7553 24.7434 0.6742
DLBCL 1.3562 20.0686 0.0000

Visualizations

Protein

View coding variants in ProteinPaint hg19 or hg38

Genome

View all variants in GenomePaint hg19 or hg38

Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2016-05-01 : Morin : DLBCL 2016-12-08 : Mansouri : PMBL 2020-07-30 : Pararajalingam : MCL

References

1.
Mansouri L, Noerenberg D, Young E, Mylonas E, Abdulla M, Frick M, Asmar F, Ljungström V, Schneider M, Yoshida K, Skaftason A, Pandzic T, Gonzalez B, Tasidou A, Waldhueter N, Rivas-Delgado A, Angelopoulou M, Ziepert M, Arends CM, Couronné L, Lenze D, Baldus CD, Bastard C, Okosun J, Fitzgibbon J, Dörken B, Drexler HG, Roos-Weil D, Schmitt CA, Munch-Petersen HD, Zenz T, Hansmann ML, Strefford JC, Enblad G, Bernard OA, Ralfkiaer E, Erlanson M, Korkolopoulou P, Hultdin M, Papadaki T, Grønbæk K, Lopez-Guillermo A, Ogawa S, Küppers R, Stamatopoulos K, Stavroyianni N, Kanellis G, Rosenwald A, Campo E, Amini RM, Ott G, Vassilakopoulos TP, Hummel M, Rosenquist R, Damm F. Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma. Blood. 2016 Dec 8;128(23):2666–2670.
2.
Morin RD, Assouline S, Alcaide M, Mohajeri A, Johnston RL, Chong L, Grewal J, Yu S, Fornika D, Bushell K, Nielsen TH, Petrogiannis-Haliotis T, Crump M, Tosikyan A, Grande BM, MacDonald D, Rousseau C, Bayat M, Sesques P, Froment R, Albuquerque M, Monczak Y, Oros KK, Greenwood C, Riazalhosseini Y, Arseneault M, Camlioglu E, Constantin A, Pan-Hammarstrom Q, Peng R, Mann KK, Johnson NA. Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas. Clin Cancer Res. 2016 May 1;22(9):2290–2300.
3.
Mansouri L, Sutton LA, Ljungström V, Bondza S, Arngården L, Bhoi S, Larsson J, Cortese D, Kalushkova A, Plevova K, Young E, Gunnarsson R, Falk-Sörqvist E, Lönn P, Muggen AF, Yan XJ, Sander B, Enblad G, Smedby KE, Juliusson G, Belessi C, Rung J, Chiorazzi N, Strefford JC, Langerak AW, Pospisilova S, Davi F, Hellström M, Jernberg-Wiklund H, Ghia P, Söderberg O, Stamatopoulos K, Nilsson M, Rosenquist R. Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia. J Exp Med. 2015 Jun 1;212(6):833–843. PMCID: PMC4451125
4.
Pararajalingam P, Coyle KM, Arthur SE, Thomas N, Alcaide M, Meissner B, Boyle M, Qureshi Q, Grande BM, Rushton C, Slack GW, Mungall AJ, Tam CS, Agarwal R, Dawson SJ, Lenz G, Balasubramanian S, Gascoyne RD, Steidl C, Connors J, Villa D, Audas TE, Marra MA, Johnson NA, Scott DW, Morin RD. Coding and noncoding drivers of mantle cell lymphoma identified through exome and genome sequencing. Blood. 2020 Jul 30;136(5):572–584. PMCID: PMC7440974

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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