NFKBIA

Overview

NFKBIA encodes IκBα, an inhibitor of NF-κB, which regulates the NF-κB signaling pathway by preventing the translocation of NF-κB to the nucleus. Mutations in NFKBIA can disrupt this regulation, leading to constitutive activation of NF-κB signaling, which has an important role in a subset of DLBCLs. Mutations and deletions in NFKBIA are observed in DLBCL and are associated with constitutive activation of the NF-κB pathway. These mutations often occur in the ABC subtype and are associated with the ST2 genetic subgroup of DLBCL.¹ ## History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2009-09-15 : Lake : DLBCL 2019-12-10 : Wienand : PMBL 2023-07-26 : Russler-Germain : FL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene
	1	high-confidence DLBCL gene
	2	relevance in FL not firmly established

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	4.40
DLBCL	Schmitz cohort	3.83
DLBCL	Reddy cohort	3.60
DLBCL	Chapuy cohort	4.70
FL	GAMBL genomes	0.69

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	No	3.358	17.442
DLBCL	No	Yes	9.385	40.878
FL	No	No	0.000	28.519

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

NFKBIA Expression

References

Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, Jiang A, Bagaev A, Plotnikova O, Kotlov N, Johnson CA, Wilson WH, Scott DW, Staudt LM. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020 Apr 13;37(4):551-568.e14. doi: 10.1016/j.ccell.2020.03.015. PMID: 32289277; PMCID: PMC8459709.
Lake A, Shield LA, Cordano P, Chui DTY, Osborne J, Crae S, Wilson KS, Tosi S, Knight SJL, Gesk S, Siebert R, Hay RT, Jarrett RF. Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases. Int J Cancer. 2009 Sep 15;125(6):1334–1342. PMID: 19507254
Wienand K, Chapuy B, Stewart C, Dunford AJ, Wu D, Kim J, Kamburov A, Wood TR, Cader FZ, Ducar MD, Thorner AR, Nag A, Heubeck AT, Buonopane MJ, Redd RA, Bojarczuk K, Lawton LN, Armand P, Rodig SJ, Fromm JR, Getz G, Shipp MA. Genomic analyses of flow-sorted Hodgkin Reed-Sternberg cells reveal complementary mechanisms of immune evasion. Blood Adv. 2019 Dec 10;3(23):4065–4080. PMCID: PMC6963251
Russler-Germain DA, Krysiak K, Ramirez CA, Mosior M, Watkins MP, Gomez F, Skidmore ZL, Trani L, Gao F, Geyer S, Cashen A, Mehta-Shah N, Kahl B, Bartlett N, Alderuccio J, Lossos I, Ondrejka S, Hsi E, Martin P, Leonard J, Griffith M, Griffith O, Fehniger T. Mutations associated with progression in follicular lymphoma predict inferior outcomes at diagnosis: Alliance A151303. Blood Advances. 2023;7:5524–5539.