Alt. symbols: CD283

Approved name: toll like receptor 3
Alt. names: toll-like receptor 3

Location: 4q35.1: 186068911 - 186088073 (+)
Gene type: protein_coding, 9 transcripts.

Scores: LoFtool: 0.780000 | pLI: 0.00121124 | LOEUF: 0.801

HGNC: 11849

NCBI: 7098, RefSeq: NG_007278.1

Ensembl: ENSG00000164342.14

LRG_117 | Status: public

OMIM: 603029

Expression | ProteinAtlas

Toll-like receptor 3 (TLR3), also known as CD283, is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved across species since they recognize pathogen-associated molecular patterns (PAMPs) expressed by infectious agents. When activated, they mediate the production of the cytokines necessary for the development of effective immunity. TLR3 is most abundantly expressed in placenta, pancreas and the central nervous system (CNS), and is restricted to dendritic cells in leukocytes. TLR3 is a nucleotide-sensing TLR, as it recognizes dsRNA associated with viral infection. Upon engagement it induces the activation of NF-kappaB, the nuclear translocation of IRF3, and the production of type I interferons. It may thus play a role in host defence against viruses.

At least 10 different mutations have been associated with TLR3 deficiency in humans (PMID: 21911422, 25339207, 26513235, 28368532, 23290562, 31217193, 32936395). TLR3 deficiency was first described in 2007 as an autosomal dominant form of herpes simplex virus 1 (HSV-1) encephalitis (HSE), caused by a dominant-negative variant (p.P554S) (PMID: 17872438). However, in 2011, complete TLR3 deficiency was also reported as an autosomal recessive form of HSE (PMID: 21911422) in a patient with the p.P554 S allele and the p.E746X allele. Patient's fibroblasts had an impaired IFN-beta and IFN-lambda response upon HSV-1 infection, but they responded normally in other TLR3-deficient leukocyte subpopulations, thus showing a specific effect on epithelial cells expressing TLR3. The findings suggested a protective role of TLR3 against HSV-1 in the CNS during primary infection in childhood (PMID: 21911422). Subsequent publications from 2014 to 2107 have reported additional cases with HSE caused by monoallelic or biallelic SNV in TLR3 (PMID: 25339207,26513235, 28368532). In all families described in these studies there is an incomplete disease penetrance, that is, many carriers do not develop HSE. This could likely be attributed to additional factors such as the age at infection with HSV-1, the viral inoculum, or modifier genes. However patients with meningoencephalitis or encephalitis due to varicella zoster virus (VZV) (PMID: 28368532) or hantavirus (PMID: 32936395); or cases of severe pneumonitis due to influenza A (IAV) infection (PMID: 31217193) have also been reported. Other groups have shown that polymorphisms in TLR3, like the p.L412F, could confer protection against HIV1 infection (PMID: 22174453). [Load More]