IkBA variant leads to EDA-ID

Stable Identifier
R-HSA-5603029
Type
Pathway
Species
Homo sapiens
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The nuclear factor kappa B (NFkB) family of transcription factors is kept inactive in the cytoplasm by the inhibitor of kappa B (IkB) family members IKBA (IkB alpha, NFKBIA), IKBB (IkB beta, NFKBIB) and IKBE (IkB epsilon, NFKBIE) (Oeckinghaus A and Ghosh S 2009). Multiple stimuli such as inflammatory cytokines, microbial products or various types of stress activate NFkB signaling leading to stimuli-induced phosphorylation of IkB molecule (Scherer DC et al. 1995; Alkalay I et al. 1995; Lawrence T 2009; Hoesel B and Schmid JA 2013). The phosphorylation of IkB proteins triggers their polyubiquitination and subsequent degradation by 26S proteasome, allowing free NFkB dimer to translocate to the nucleus where it directs the expression of target genes. Studies have identified an autosomal dominant form of ectodermal dysplasia with immunodeficiency (AD-EDA-ID) caused by a hypermorphic heterozygous mutation of NFKBIA/IKBA gene. The IKBA defects prevent the phosphorylation and degradation of IKBA protein resulting in gain-of-function condition with the enhanced inhibitory capacity of IKBA in sequestering NF?B dimers in the cytoplasm (Courtois G et al. 2003; Lopes-Granados E et al. 2008; Schimke LF et al. 2013).

Literature References
PubMed ID Title Journal Year
23708964 A novel gain-of-function IKBA mutation underlies ectodermal dysplasia with immunodeficiency and polyendocrinopathy

Schimke, LF, Rieber, N, Rylaarsdam, S, Cabral-Marques, O, Hubbard, N, Puel, A, Kallmann, L, Sombke, SA, Notheis, G, Schwarz, HP, Kammer, B, Hökfelt, T, Repp, R, Picard, C, Casanova, JL, Belohradsky, BH, Albert, MH, Ochs, HD, Renner, ED, Torgerson, TR

J. Clin. Immunol. 2013
18412279 A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency

Lopez-Granados, E, Keenan, JE, Kinney, MC, Leo, H, Jain, N, Ma, CA, Quinones, R, Gelfand, EW, Jain, A

Hum. Mutat. 2008
Participants
Participant Of
Disease
Name Identifier Synonyms
primary immunodeficiency disease 612 immune deficiency disorder, immunodeficiency syndrome, hypoimmunity
Cross References
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