Alt. symbols: LYT-10 | p52 | p105 | NF-kB2 | p49/p100

Approved name: nuclear factor kappa B subunit 2
Alt. names: nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)

Location: 10q24.32: 102394110 - 102402524 (+)
Gene type: protein_coding, 20 transcripts.

Scores: LoFtool: 0.180000 | pLI: 0.99969646 | LOEUF: 0.163

HGNC: 7795

NCBI: 4791, RefSeq: NG_033874.2

Ensembl: ENSG00000077150.21

LRG_1347 | Status: public

OMIM: 164012

Expression | ProteinAtlas

NFKB2 encodes a subunit of the transcription factor complex nuclear factor-kappa-B (NFkB). The NFkB complex is expressed in numerous cell types and functions as a central activator of genes involved in inflammation and immune function. The protein encoded by this gene can function as both a transcriptional activator or repressor depending on its dimerization partner. The p100 full-length protein is co-translationally processed into a p52 active form. Chromosomal rearrangements and translocations of this locus have been observed in B cell lymphomas, some of which may result in the formation of fusion proteins.

Under the umbrella of autosomal dominant condition CVID type 10 [OMIM: 615577] resides a broad spectrum of NFKB2 mutations associated with various pathophysiologies and phenotypic variants of CVID. Monoallelic C-terminal mutations lead to transcripts that escape NMD and result in truncated proteins that lose phosphorylation sites important for p100 interaction with and proteolytic processing by NF-κB-inducing kinase (NIK), resulting in unprocessed, repressive p100 instead of activating p52 - a DN effect (PMID: 25524009, 31417880). Other C-terminal truncating mutations lead to increased nuclear accumulation of p52 - a GOF effect. However, both types of mutations can be associated with a similar combination of phenotypes involving CVID along with autoimmunity, adrenal insufficiency and/or ectodermal dysplasia. Some of these C-terminal mutations leading to abnormal non-canonical NF-κB signaling not only disrupt B cell function, but have also been reported to cause abnormal T cell and NK cell function (PMID: 25205549, 25605273, 27749582, 31417880). On the other hand, more N-terminal monoallelic predicted LOF mutations in regions such as the Ankyrin domains can cause an uncomplicated CVID phenotype or CVID with autoimmunity alone. [Load More]