NFKBIE

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 ## 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

## Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene
	1	high-confidence DLBCL gene
	1	high-confidence MCL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	3.82
DLBCL	Schmitz cohort	5.74
DLBCL	Reddy cohort	2.90
DLBCL	Chapuy cohort	3.42
MCL	GAMBL genomes	2.84

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	No	2.702	0.000
DLBCL	No	Yes	8.732	58.269
FL	No	No	0.000	46.628

[!NOTE] First described in DLBCL in 2016 by Morin RD. First described in MCL in 2020 by Pararajalingam P

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

NFKBIE Expression

References

Mansouri, L., Noerenberg, D., Young, E., Mylonas, E., Abdulla, M., Frick, M., Asmar, F., Ljungström, V., Schneider, M., Yoshida, K., Skaftason, A., Pandzic, T., González, B., Tasidou, A., Waldhueter, N., Rivas-Delgado, A., Angelopoulou, M., Ziepert, M., Arends, C., Couronné, L., Lenze, D., Baldus, C., Bastard, C., Okosun, J., Fitzgibbon, J., Dörken, B., Drexler, H., Roos-Weil, D., Schmitt, C., Munch-Petersen, H., Zenz, T., Hansmann, M., Strefford, J., Enblad, G., Bernard, O., Ralfkiaer, E., Erlanson, M., Korkolopoulou, P., Hultdin, M., Papadaki, T., Grønbæk, K., López-Guillermo, A., Ogawa, S., Küppers, R., Stamatopoulos, K., Stavroyianni, N., Kanellis, G., Rosenwald, A., Campo, E., Amini, R., Ott, G., Vassilakopoulos, T., Hummel, M., Rosenquist, R., & Damm, F. (2016). Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma.. Blood, 128 23, 2666-2670 . https://doi.org/10.1182/BLOOD-2016-03-704528.
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. doi: 10.1182/blood.2019002385. PMID: 32160292; PMCID: PMC7440974.