Covered on Genetics Home Reference: common variable immune deficiencyFrom NCBI Gene: Common variable immunodeficiency 10From UniProt: A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which codes for a truncated 80 kDa protein (p80HT). A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant. In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions. Immunodeficiency, common variable, 10 (CVID10): A primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B-cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency. [MIM:615577]

     From NCBI Gene: This gene 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. There is a pseudogene for this gene on chromosome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013] From UniProt: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.

The following transcription factors affect gene expression:

• NF-kappaB2
• GATA-2
• STAT3
• p53

Molecular Function:

• Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
• Transcriptional Activator Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
• Chromatin Binding
• Transcription Factor Activity, Sequence-Specific Dna Binding
• Transcription Coactivator Activity

Biological Processes:

• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Follicular Dendritic Cell Differentiation
• Germinal Center Formation
• Regulation Of Transcription, Dna-Templated
• Inflammatory Response
• I-Kappab Kinase/Nf-Kappab Signaling
• Aging
• Extracellular Matrix Organization
• Positive Regulation Of Type I Interferon Production
• Response To Lipopolysaccharide
• Response To Cytokine
• Nik/Nf-Kappab Signaling
• Innate Immune Response
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Rhythmic Process
• Spleen Development
• Positive Regulation Of Nf-Kappab Transcription Factor Activity

Drug Bank:

• Acetylsalicylic Acid
• Glucosamine