TLR3 Gene: Toll-Like Receptor 3
Key innate immune sensor for double-stranded RNA, implicated in antiviral defense and autoimmune disease
Gene Information Card
| Symbol | TLR3 |
|---|---|
| Full Name | Toll Like Receptor 3 |
| Gene Type | protein coding |
| Chromosomal Location | 4q35.1 |
| NCBI Gene ID | 7098 ncbi.nlm.nih.gov/gene/7098 |
| Ensembl ID | ENSG00000164342 |
| UniProt ID | O15455 |
| OMIM ID | 603029 |
| HGNC ID | 11849 |
| Aliases | CD283, IIAE5, IMD83 |
Description
The TLR3 gene encodes Toll-like receptor 3, a member of the Toll-like receptor family that plays a critical role in innate immune recognition. TLR3 specifically detects double-stranded RNA (dsRNA), a molecular pattern associated with viral infection, and triggers signaling cascades that lead to the production of type I interferons and inflammatory cytokines. This receptor is expressed primarily in endosomal compartments of immune cells and also in various non-immune tissues. Mutations in TLR3 are linked to increased susceptibility to viral infections, particularly herpes simplex encephalitis, and have been implicated in autoimmune and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Herpes simplex encephalitis | Loss-of-function mutations impair TLR3-mediated type I interferon response, leading to uncontrolled HSV-1 replication in the CNS. | ClinVar, OMIM |
| Influenza A virus infection | TLR3 deficiency may increase severity of influenza infection due to impaired antiviral response. | ClinVar, PubMed |
| Systemic lupus erythematosus | TLR3 activation by endogenous RNA may contribute to aberrant interferon production and autoimmunity. | OMIM, PubMed |
| Autoimmune thyroid disease | Polymorphisms in TLR3 have been associated with increased risk of Graves' disease and Hashimoto's thyroiditis. | PubMed |
| Viral myocarditis | TLR3 signaling influences cardiac inflammation and viral clearance in coxsackievirus infection. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 5.2 | Low |
| Spleen | 4.1 | Low |
| Liver | 3.8 | Low |
| Brain | 2.5 | Not detected |
| Kidney | 1.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 12.3 | High expression; responds to poly(I:C) |
| A549 (lung epithelial) | 8.7 | Moderate expression; involved in antiviral response |
| HeLa (cervical) | 6.4 | Moderate expression |
| HepG2 (liver) | 3.2 | Low expression |
| K562 (leukemia) | 1.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1660C>T (p.Pro554Ser) | Missense | Rare (MAF <0.01) | Impaired TLR3 signaling; associated with HSE susceptibility |
| c.2236C>T (p.Arg740Cys) | Missense | Rare | Loss of function; reduces dsRNA binding and signaling |
| c.2404G>A (p.Glu802Lys) | Missense | Rare | Dominant-negative effect; disrupts TLR3 trafficking |
| c.1377C>A (p.Tyr459Ter) | Nonsense | Very rare | Truncated protein; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TLR3 impair dsRNA recognition and downstream signaling, leading to reduced type I interferon production and increased susceptibility to viral infections, particularly herpes simplex encephalitis.
Gain of Function (GOF)
Gain-of-function mutations are rare but may lead to enhanced TLR3 signaling, potentially contributing to excessive inflammation and autoimmune pathology.
Dominant Negative (DN)
Dominant-negative mutations, such as p.Glu802Lys, interfere with wild-type TLR3 function by disrupting receptor dimerization or trafficking, leading to haploinsufficiency and increased infection risk.
View complete mutation data：
Gene Ontology (GO)
| • double-stranded RNA binding | • protein heterodimerization activity |
| • innate immune response | • signal transduction |
| • inflammatory response | • endosome |
| • plasma membrane | • response to virus |
| • I-kappaB kinase/NF-kappaB signaling | • positive regulation of type I interferon production |
Pathways
• Toll-like receptor signaling pathway
• RIG-I-like receptor signaling pathway
• Cytosolic DNA-sensing pathway
• Innate Immune System
• Herpes simplex infection
Protein Summary
TLR3 is a type I transmembrane protein of 904 amino acids with an extracellular domain containing leucine-rich repeats that recognize dsRNA, a transmembrane domain, and a cytoplasmic Toll/interleukin-1 receptor (TIR) domain. Upon binding dsRNA in endosomes, TLR3 recruits the adaptor protein TICAM1 (TRIF), leading to activation of IRF3 and NF-κB, which induce type I interferons and pro-inflammatory cytokines. The protein is ubiquitously expressed but most abundant in immune cells and tissues exposed to pathogens. Post-translational modifications include glycosylation and ubiquitination, which regulate its stability and signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TLR3 Knockout HEK293 Cell Line | EDJ-KQ15746 | Human | 7098 | Details Get a Quote |
| TLR3 Knockout HCT 116 Cell Line | EDJ-KQ46668 | Human | 7098 | Details Get a Quote |
| TLR3 Knockout HeLa Cell Line | EDJ-KQ46669 | Human | 7098 | Details Get a Quote |
| TLR3 Knockout A-431 Cell Line | EDJ-KZ510 | Human | 7098 | Details Get a Quote |
| TLR3 Knockout A-549 Cell Line | EDJ-KQ63148 | Human | 7098 | Details Get a Quote |
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