TLR3

Chr 4ADAR

toll like receptor 3

Also known as: CD283, IIAE2, IMD83

NCBI Gene: 7098ENSG00000164342UniProt: O15455OMIM: 603029

The protein encoded by this gene 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 from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It thus plays a role in host defense against multiple viruses. [provided by RefSeq, Jul 2021]

OMIMResearchGenerating clinical summary…
MultiplemechanismAD/ARLOEUF 0.802 OMIM phenotypes
Clinical Summary— TLR3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
397 VUS of 590 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.80LOEUF
pLI 0.000
Z-score 2.41
OE 0.53 (0.36–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.51Z-score
OE missense 0.93 (0.86–1.01)
427 obs / 457.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.53 (0.36–0.80)
0≤0.351.4
Missense OE?0.93 (0.86–1.01)
0≤0.61.4
Synonymous OE?1.03
0≤1.21.6
LoF obs/exp: 16 / 30.3Missense obs/exp: 427 / 457.9Syn Z: -0.31

This gene — mechanism propensity

DN
0.74top 25%
GOF
0.75top 25%
LOF
0.2386th %ile

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.

GOFprediction above median
DNprediction above median

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

590 submitted variants in ClinVar

ClinVar

Classification Summary

VUS397
Likely Benign166
Benign17
Conflicting5
397
VUS
166
Likely Benign
17
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
32
355
8
2
397
Likely Benign
0
8
20
138
166
Benign
0
5
5
7
17
Conflicting
—5
Total3236833147585

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

118 pathogenic / likely-pathogenic (of 144) ClinVar copy-number / structural variants overlap TLR3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients