Alt. symbols: TRIF | TICAM-1 | MGC35334 | PRVTIRB

Approved name: TIR domain containing adaptor molecule 1
Alt. names: toll-like receptor adaptor molecule 1 | TIR domain-containing adapter molecule 1, TIR domain-containing adaptor-inducing interferon-?

Location: 19p13.3: 4815932 - 4831712 (-)
Gene type: protein_coding, 1 transcripts.

Scores: LoFtool: 0.350000 | pLI: 0.85247731 | LOEUF: 0.000

HGNC: 18348

NCBI: 148022, RefSeq: NG_031998.1

Ensembl: ENSG00000127666.11

LRG_358 | Status: public

OMIM: 607601

Expression | ProteinAtlas

This gene encodes TRIF an adaptor protein containing a Toll/interleukin-1 receptor (TIR) homology domain, which mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. TRIF is involved in native immunity against invading pathogens because it interacts directly with toll-like receptor 3 (TLR3) and TLR5, and indirectly (through TRAM) with TLR4. TRIF then transmits the signalling cascade to TRAF molecules (TRAF3, TRAF6) which mediate the induction of type-1-interferon and the production of inflammatory cytokines through NFkB activation, during an antiviral immune response.

Both monoallelic and biallelic mutations in TICAM1 have been associated with herpes simplex encephalitis (HSE) type 6 [MIM:614850]. In 2011, Sancho-Shimizu and colleagues reported 2 unrelated HSE cases (with no other infections) due to TRIF deficiency. The first case was a boy born to a consanguineous family, who carried a homozygous nonsense mutation (p.R141X) that resulted in a complete absence of the TRIF protein. The authors showed that both the TLR3- and the (TRIF-dependent) TLR4 signalling pathways were abolished. The second case was a girl who carried an heterozygous missense mutation (p.S186L) which had been transmitted in the family in an autosomal dominant manner. This mutation led to an impaired TLR3 signalling but did not alter the TLR4 pathway. However, both patients displayed reduced capacity to respond to stimulation of the DExD/H-box helicases pathway. In the second family, the mutation showed incomplete penetrance. In 2015, Mork et al. reported 2 individuals with adult-onset HSE who respectively carried the p.A568T and the p.S160F missense mutations; thus suggesting that TICAM1 mutation may also confer susceptibility to HSE in adulthood. [Load More]