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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TLR6
toll like receptor 6
Chromosome 4 · 4p14
NCBI Gene: 10333Ensembl: ENSG00000174130.14HGNC: HGNC:16711UniProt: B2R933
175PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
detection of diacyl bacterial lipopeptideantibacterial innate immune responsenegative regulation of interleukin-8 productioncellular response to oxidised low-density lipoprotein particle stimulusresponse to stimulusasthmainborn error of immunityleprosy
✦AI Summary

TLR6 is a plasma membrane-localized pattern recognition receptor that plays a critical role in innate immune responses to gram-positive bacteria and fungi by recognizing diacylated lipopeptides 1. Upon ligand binding, TLR6 forms an activation complex with TLR2, CD14, and CD36 at the cell surface, which translocates to the Golgi in a lipid-raft-dependent manner 2. This triggers MyD88 and TRAF6-dependent signaling, activating NF-κB and promoting inflammatory cytokine secretion 1. TLR6 cooperatively recognizes multiple bacterial ligands including mycoplasmal MALP-2, tuberculosis factor, and Borrelia burgdorferi OspA-lipoprotein with TLR2 3. Additionally, TLR6 heterodimerizes with TLR4 to promote sterile inflammation in response to oxidized low-density lipoprotein and amyloid-beta 42, triggering NF-κB-dependent chemokine production 1. In lung adenocarcinoma, TLR6 overexpression is associated with neutrophil pro-tumor polarization, suggesting a pathological role in cancer progression 4. TLR6 polymorphisms (P249S) have been linked to increased susceptibility to complicated skin infections 5, indicating that genetic variation affects host defense capacity 6.

Sources cited
1
TLR6 recognizes diacylated and triacylated lipopeptides; forms TLR2:TLR6:CD14:CD36 activation cluster; signals via MyD88/TRAF6 to activate NF-κB; recognizes bacterial ligands cooperatively with TLR2; heterodimerizes with TLR4 in response to oxLDL and amyloid-beta
PMID: 20037584
2
TLR2:TLR6 activation cluster undergoes lipid-raft dependent translocation to the Golgi
PMID: 16880211
3
TLR6 cooperatively recognizes mycoplasmal MALP-2, tuberculosis factor, and B. burgdorferi OspA-lipoprotein with TLR2
PMID: 11441107
4
TLR6 is overexpressed in lung adenocarcinoma and associated with neutrophil pro-tumor effects
PMID: 38204755
5
TLR6 P249S polymorphism is associated with increased susceptibility to complicated skin and skin structure infections
PMID: 24511099
6
TLR6 polymorphisms influence disease susceptibility through effects on innate immunity
PMID: 25784622
Disease Associationsⓘ20
response to stimulusOpen Targets
0.48Moderate
asthmaOpen Targets
0.41Moderate
inborn error of immunityOpen Targets
0.37Weak
leprosyOpen Targets
0.34Weak
chronic rhinosinusitisOpen Targets
0.28Weak
CINCA syndromeOpen Targets
0.18Weak
cardiovascular diseaseOpen Targets
0.18Weak
conjunctivitisOpen Targets
0.12Weak
Lyme diseaseOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
restless legs syndromeOpen Targets
0.07Suggestive
infectionOpen Targets
0.07Suggestive
DNA methylationOpen Targets
0.07Suggestive
colitisOpen Targets
0.07Suggestive
Spirochaetales InfectionsOpen Targets
0.07Suggestive
dengue diseaseOpen Targets
0.07Suggestive
azoospermiaOpen Targets
0.06Suggestive
breast cancerOpen Targets
0.06Suggestive
movement disorderOpen Targets
0.05Suggestive
obstructive sleep apneaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SCARB1Protein interaction100%SCARB2Protein interaction100%HSPA9Protein interaction100%TLR5Protein interaction100%TIRAPProtein interaction100%CLEC7AProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
77%
Liver
30%
Ovary
24%
Brain
19%
Heart
16%
Gene Interaction Network
Click a node to explore
TLR6SCARB1SCARB2HSPA9TLR5TIRAPCLEC7A
PROTEIN STRUCTURE
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PDB4OM7 · 2.20 Å · X-ray
View on RCSB ↗
RankingsWhere TLR6 stands among ~20K protein-coding genes
  • #2,512of 20,598
    Most Researched175 · top quartile
Genes detectedTLR6
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
TLR10 and Its Role in Immunity.
PMID: 34595581
Handb Exp Pharmacol · 2022
1.00
2
Sequence variants in the TLR4 and TLR6-1-10 genes and prostate cancer risk. Results based on pooled analysis from three independent studies.
PMID: 20200442
Cancer Epidemiol Biomarkers Prev · 2010
0.90
3
Neutrophil infiltration associated genes on the prognosis and tumor immune microenvironment of lung adenocarcinoma.
PMID: 38204755
Front Immunol · 2023
0.80
4
Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk.
PMID: 15812078
J Natl Cancer Inst · 2005
0.80
5
Gene conversion limits divergence of mammalian TLR1 and TLR6.
PMID: 17727694
BMC Evol Biol · 2007
0.70