TICAM1 deficiency blocks TLR3 pathway

Stable Identifier
Reaction [transition]
Homo sapiens
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Toll/IL-1R (TIR) domain-containing adaptor inducing IFN-beta (TRIF) protein, also known as TIR domain-containing adaptor molecule 1 (TICAM1), functions as an adaptor molecule in TLR3 and TLR4 signaling pathways. TRIF recruits to the activated receptor complex the downstream mediators such as TRAF3, TANK-binding kinase 1 (TBK1), receptor-interacting protein 1 (RIP1) and IFN regulatory factor 3 (IRF3). Sequencing the TRIF gene in a cohort of children with herpes simplex virus type 1 (HSV1) encephalitis (HSE) revealed two abnormalities that may predispose to HSE (Sancho-Shimizu V et al. 2011). The autosomal recessive form of TRIF deficiency was found to be due to a homozygous nonsense mutation (R141*) that resulted in a complete absence of the TRIF protein. Both the TLR3- and the TRIF-dependent TLR4 signaling pathways were abolished. The autosomal dominant form of the disease was found to be due to a heterozygous missense mutation (S186L), resulting in a dysfunctional protein. In this form of the disease, the TLR3 signaling pathway was impaired, whereas the TRIF-dependent TLR4 pathway was unaffected (Sancho-Shimizu V et al. 2011).

Literature References
PubMed ID Title Journal Year
22105173 Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency

Alkhamis, N, Abel, L, Halwani, R, Ghadiri, A, Lebon, P, Al-Muhsen, S, Alangari, A, Lorenzo, L, Maluenda, J, Plancoulaine, S, Mahvelati, F, Cardon, A, Rozenberg, F, Sancho-Shimizu, V, Al-Makadma, AS, Ciancanelli, M, Chaussabel, D, Fabrega, S, Rezaei, N, AlSum, Z, PĂ©rez de Diego, R, Herman, M, Seya, T, Jouanguy, E, Matsumoto, M, Puel, A, Picard, C, Boucherit, S, Tatematsu, M, Zhang, SY, Guo, Y, Casanova, JL, Israelsson, E, Tardieu, M

J. Clin. Invest. 2011
Normal reaction
Functional status

Loss of function of TICAM1 variants [cytosol]

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