TLR4
Chr 9toll like receptor 4
Also known as: ARMD10, CD284, TLR-4, TOLL
The TLR4 protein functions as a transmembrane pattern recognition receptor that recognizes bacterial lipopolysaccharide and other pathogen-associated molecular patterns to activate innate immune responses and cytokine production. Mutations in TLR4 have been associated with altered lipopolysaccharide responsiveness and susceptibility to infectious diseases, though well-defined Mendelian disorders are not established. This gene shows very low constraint against loss-of-function variants, suggesting that complete loss of TLR4 function may be tolerated in humans.
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 (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TLR4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Adipose Tissue and Inflammation in Coronary Heart Disease
ACTIVE NOT RECRUITINGTributyrin Treatment in Mild Alzheimer Disease: Assessment of Butyrate Effects Via the Gut-Brain
NOT YET RECRUITINGThe Role of Toll-like Receptor-4 in Periodontitis Patients With End-stage Renal Disease in a Sample of Egyptian Population
RECRUITINGEvaluation of the Effect of Smoking on Pyroptosis in Periodontal Pathogenesis
ACTIVE NOT RECRUITINGThe Effect of Quadratus Lumborum (QL) Block on the Incidence of Chronic Neuropathic Pain After Retroperitoneal Laparoscopic Donor Nephrectomy: A Study on Neuroinflammation and Neurophysiology
NOT YET RECRUITINGA Randomized, Double-Blind, Placebo Controlled Study to Assess the Efficacy and Safety of SNP-610 for the Treatment of Patients With Non-alcoholic Steatohepatitis
NOT YET RECRUITINGAssessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components
ACTIVE NOT RECRUITINGStudy of the Effect of Innate on the Inflammatory Response to Endotoxin
RECRUITINGEffects of Propolis Flavonoids on TLR4 Signaling and Inflammation in Human PDLSCs In Vitro
NOT YET RECRUITINGThe Developmental Origins of Obesity
RECRUITINGExternal Resources
Links to major genomics databases and tools