TLR9 Gene (Toll Like Receptor 9)
Key innate immune sensor for microbial DNA, implicated in infectious and autoimmune diseases
Gene Information Card
| Symbol | TLR9 |
|---|---|
| Full Name | Toll Like Receptor 9 |
| Gene Type | protein coding |
| Chromosomal Location | 3p21.2 |
| NCBI Gene ID | 54106 ncbi.nlm.nih.gov/gene/54106 |
| Ensembl ID | ENSG00000173366 |
| UniProt ID | Q9NR96 |
| OMIM ID | 605474 |
| HGNC ID | 15633 |
| Aliases | CD289 |
Description
TLR9 (Toll-like receptor 9) is a transmembrane receptor that plays a critical role in innate immunity by recognizing unmethylated CpG dinucleotides in microbial DNA. Upon activation, it triggers signaling cascades leading to the production of pro-inflammatory cytokines and type I interferons. TLR9 is primarily expressed in endosomal compartments of immune cells such as plasmacytoid dendritic cells and B cells. It is involved in defense against bacterial and viral infections, and its dysregulation has been linked to autoimmune diseases, cancer, and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic lupus erythematosus (SLE) | TLR9 activation by self-DNA-containing immune complexes leads to type I interferon production and autoantibody generation. | ClinVar, OMIM |
| Infectious diseases (e.g., bacterial sepsis) | TLR9 recognizes bacterial CpG DNA, triggering pro-inflammatory responses that can contribute to sepsis pathology. | NCBI Gene, PubMed |
| Cancer (e.g., gastric cancer) | TLR9 expression in tumor cells may promote tumor progression via NF-κB activation and cytokine secretion. | COSMIC, PubMed |
| Asthma | TLR9 polymorphisms may influence susceptibility to asthma and allergic inflammation. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 10.2 | Medium |
| Lymph node | 8.5 | Medium |
| Bone marrow | 7.1 | Low |
| Lung | 3.4 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Plasmacytoid dendritic cells | High | Key TLR9-expressing cells |
| B lymphocytes | Medium | TLR9 activation induces B cell proliferation |
| Monocytes | Low | Expression inducible by stimulation |
| HEK293 | Not detected | Common cell line for transfection studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs5743836 (promoter variant) | SNP | ~20% in some populations | May affect TLR9 expression and disease susceptibility |
| rs352140 (missense variant) | SNP | ~30% in some populations | Alters receptor function; associated with autoimmune risk |
| c.1635A>G (p.Ile545Val) | Missense | Rare | Reported in ClinVar; functional impact uncertain |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TLR9 are rare; they may impair CpG recognition and reduce cytokine responses, leading to increased susceptibility to certain infections.
Gain of Function (GOF)
Gain-of-function variants could enhance TLR9 signaling, potentially contributing to excessive inflammation and autoimmunity, though specific variants are not well characterized.
Dominant Negative (DN)
Dominant-negative effects have not been clearly documented for TLR9; however, some variants may interfere with receptor dimerization or signaling.
View complete mutation data：
Gene Ontology (GO)
| • pattern recognition receptor activity | • CpG DNA binding |
| • innate immune response | • signal transduction |
| • inflammatory response | • endosome membrane |
Pathways
• Toll-like receptor signaling pathway
• MyD88-dependent pathway
• NF-kappa B signaling
• Cytosolic DNA-sensing pathway
Protein Summary
TLR9 is a type I transmembrane protein with an extracellular leucine-rich repeat domain and a cytoplasmic Toll/IL-1 receptor (TIR) domain. It resides in the endoplasmic reticulum and translocates to endosomes upon stimulation. The protein recognizes unmethylated CpG DNA, leading to recruitment of MyD88 and activation of IRAK kinases, ultimately triggering NF-κB and IRF7 pathways. This results in the production of pro-inflammatory cytokines and type I interferons. TLR9 is crucial for immune defense against pathogens and is a target for therapeutic modulation in autoimmune diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TLR9 Knockout HEK293 Cell Line | EDJ-KQ51358 | Human | 54106 | Details Get a Quote |
| TLR9 Knockout HeLa Cell Line | EDJ-KQ56397 | Human | 54106 | Details Get a Quote |
| TLR9 Knockout A-549 Cell Line | EDJ-KQ64889 | Human | 54106 | Details Get a Quote |
| TLR9 Knockout HCT 116 Cell Line | EDJ-KQ73333 | Human | 54106 | Details Get a Quote |
