Defective UNC93B1 does not bind TLR3

Stable Identifier
Reaction [transition]
Homo sapiens
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The 1034del4 and 781G>A mutations in the coding region of UNC93B1 gene both result in a premature termination codon, leading to a complete loss of UNC93B1 expression and function due to nonsense-mediated mRNA decay (Casrouge A et al. 2006). Under normal conditions UNC96B functions as a chaperone delivering nucleotide-sensing toll-like receptors TLR3, TLR7-9 from the endoplasmic reticulum to the endosome (Kim YM et al. 2008). Autosomal recessive UNC93B1 deficiency in patients may contribute to pathogenesis of herpes simplex virus type 1 (HSV1) encephalitis (HSE) due to impaired production of IFN-alpha, beta and gamma in cells of central nervous system(CNS) via TLR3-mediated immune response to HSV1 (Casrouge A et al. 2006; Lafaille FG et al. 2012).

Literature References
PubMed ID Title Journal Year
16973841 Herpes simplex virus encephalitis in human UNC-93B deficiency

Beutler, B, Abel, L, Alcais, A, Dulac, O, Lebon, P, Lorenzo, L, Plancoulaine, S, Du, X, Nicolas, N, Rozenberg, F, Sénéchal, B, Miller, RL, Tabeta, K, Geissmann, F, Casrouge, A, Héron, B, Yang, K, Jouanguy, E, de Villemeur, TB, Puel, A, Picard, C, Eidenschenk, C, Mignot, C, Zhang, SY, Hoebe, K, Mahfoufi, N, Casanova, JL, Tardieu, M

Science 2006
23103873 Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells

Abel, L, Ordovas-Montanes, J, Schlaeger, TM, Al-Muhsen, S, Pessach, IM, Abhyankar, A, Herman, M, Elkabetz, Y, Plancoulaine, S, Jouanguy, E, Ciancanelli, MJ, Lafaille, FG, Goldstein, PA, Studer, L, Tu, E, Keros, S, Zhang, SY, Notarangelo, LD, Mostoslavsky, G, Daley, GQ, Ying, SW, Casanova, JL, Tardieu, M

Nature 2012
Normal reaction
Functional status

Loss of function of UNC93B1 variants [endoplasmic reticulum membrane]

Name Identifier Synonyms
primary immunodeficiency disease DOID:612 immune deficiency disorder, immunodeficiency syndrome, hypoimmunity
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