TLR3
Chr 4ADARtoll like receptor 3
Also known as: CD283, IIAE2, IMD83
TLR3 encodes a Toll-like receptor that recognizes double-stranded RNA from viruses and activates innate immune responses through NF-kappaB and interferon pathways. Mutations cause immunodeficiency with increased susceptibility to viral infections, particularly severe complications from common viruses like HSV and influenza. The gene shows both autosomal dominant and autosomal recessive inheritance patterns depending on the specific variant.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
435 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 47 | 0 | 47 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 13 | 230 | 27 | 2 | 272 |
Likely Benign | 0 | 2 | 12 | 89 | 103 |
Benign | 0 | 0 | 3 | 0 | 3 |
Conflicting | — | 1 | |||
| Total | 13 | 232 | 93 | 91 | 430 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TLR3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy
RECRUITINGSKIN Disease Profiling by an Exploratory, pRospective, Biomarker Study in dermatoloGY Practice (SKINERGY)
RECRUITINGAutoantibodies Against Type I Interferon in Patients Affected With Ph-negative Myeloproliferative Neoplasms (MPN-IFN Study)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools