Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	1	1032	3p21.2	TLR9	toll like receptor 9
Mouse	1	1032	9 F1	Tlr9	toll-like receptor 9
Rat	-	-	8	Tlr9	toll-like receptor 9

Previous and Unofficial Names

CD289 | toll-like receptor 9

Database Links
Alphafold	Q9NR96 (Hs), Q9EQU3 (Mm)
CATH/Gene3D	3.40.50.10140, 3.80.10.10
ChEMBL Target	CHEMBL5804 (Hs), CHEMBL6128 (Mm)
DrugBank Target	Q9NR96 (Hs)
Ensembl Gene	ENSG00000239732 (Hs), ENSMUSG00000045322 (Mm), ENSRNOG00000048161 (Rn)
Entrez Gene	54106 (Hs), 81897 (Mm), 338457 (Rn)
Human Protein Atlas	ENSG00000239732 (Hs)
KEGG Gene	hsa:54106 (Hs), mmu:81897 (Mm), rno:338457 (Rn)
OMIM	605474 (Hs)
Pharos	Q9NR96 (Hs)
UniProtKB	Q9NR96 (Hs), Q9EQU3 (Mm)
Wikipedia	TLR9 (Hs)

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference agatolimod Hs Agonist - - 5 ⤷ [5]

Antagonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference hydroxychloroquine Hs Antagonist 7.1 pIC50 3 ⤷ pIC50 7.1 (IC50 8x10-8 M) [3] Description: Inhibition of hTLR9 CpG2006-induced luciferase reporter gene activation.

Immunopharmacology Comments

TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [4]. Activated TLR9 receptors expressed by B cells and plasmacytoid dendritic cells, stimulate human B-cell proliferation, enhance antigen-specific antibody production and induce IFN-α production, IL-10 secretion and natural killer cell activity.

Immuno Process Associations

Immuno Process:  B cell (activation) GO Annotations:  Associated to 3 GO processes GO:0030890 positive regulation of B cell proliferation IDA GO:0045577 regulation of B cell differentiation IDA GO:0050871 positive regulation of B cell activation IDA

Immuno Process:  Inflammation GO Annotations:  Associated to 12 GO processes GO:0002224 toll-like receptor signaling pathway IBA GO:0034122 negative regulation of toll-like receptor signaling pathway IDA GO:0034123 positive regulation of toll-like receptor signaling pathway IDA GO:0034163 regulation of toll-like receptor 9 signaling pathway IDA GO:0038187 pattern recognition receptor activity IBA GO:0045087 innate immune response TAS GO:0050729 positive regulation of inflammatory response IC click arrow to show/hide IEA associations GO:0001774 microglial cell activation IEA GO:0002218 activation of innate immune response IEA GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA GO:0034162 toll-like receptor 9 signaling pathway IEA GO:0034165 positive regulation of toll-like receptor 9 signaling pathway IEA

Immuno Process:  Immune system development GO Annotations:  Associated to 1 GO processes GO:0045577 regulation of B cell differentiation IDA

Immuno Process:  Immune regulation GO Annotations:  Associated to 14 GO processes GO:0002224 toll-like receptor signaling pathway IBA GO:0002639 positive regulation of immunoglobulin production IDA GO:0030890 positive regulation of B cell proliferation IDA GO:0034122 negative regulation of toll-like receptor signaling pathway IDA GO:0034123 positive regulation of toll-like receptor signaling pathway IDA GO:0034163 regulation of toll-like receptor 9 signaling pathway IDA GO:0045577 regulation of B cell differentiation IDA GO:0050729 positive regulation of inflammatory response IC GO:0050871 positive regulation of B cell activation IDA click arrow to show/hide IEA associations GO:0002218 activation of innate immune response IEA GO:0002730 regulation of dendritic cell cytokine production IEA GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA GO:0034162 toll-like receptor 9 signaling pathway IEA GO:0034165 positive regulation of toll-like receptor 9 signaling pathway IEA

Immuno Process:  Cytokine production & signalling GO Annotations:  Associated to 17 GO processes GO:0032715 negative regulation of interleukin-6 production ISS GO:0032717 negative regulation of interleukin-8 production IDA GO:0032722 positive regulation of chemokine production IDA GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production IDA GO:0032727 positive regulation of interferon-alpha production IDA GO:0032728 positive regulation of interferon-beta production IDA GO:0032729 positive regulation of type II interferon production IDA GO:0032733 positive regulation of interleukin-10 production ISS GO:0032735 positive regulation of interleukin-12 production ISS GO:0032741 positive regulation of interleukin-18 production ISS GO:0032755 positive regulation of interleukin-6 production IDA GO:0032757 positive regulation of interleukin-8 production IDA GO:0032760 positive regulation of tumor necrosis factor production ISS GO:0034163 regulation of toll-like receptor 9 signaling pathway IDA click arrow to show/hide IEA associations GO:0002730 regulation of dendritic cell cytokine production IEA GO:0034162 toll-like receptor 9 signaling pathway IEA GO:0034165 positive regulation of toll-like receptor 9 signaling pathway IEA

Immuno Process:  Chemotaxis & migration GO Annotations:  Associated to 1 GO processes GO:0032722 positive regulation of chemokine production IDA

Immuno Process:  Cellular signalling GO Annotations:  Associated to 11 GO processes GO:0002224 toll-like receptor signaling pathway IBA GO:0030890 positive regulation of B cell proliferation IDA GO:0034122 negative regulation of toll-like receptor signaling pathway IDA GO:0034123 positive regulation of toll-like receptor signaling pathway IDA GO:0034163 regulation of toll-like receptor 9 signaling pathway IDA GO:0045577 regulation of B cell differentiation IDA GO:0050871 positive regulation of B cell activation IDA click arrow to show/hide IEA associations GO:0001774 microglial cell activation IEA GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA GO:0034162 toll-like receptor 9 signaling pathway IEA GO:0034165 positive regulation of toll-like receptor 9 signaling pathway IEA

Clinically-Relevant Mutations and Pathophysiology
Disease:  Asthma, susceptibility to Disease Ontology: DOID:2841 OMIM: 600807
Disease:  Cerebral malaria Synonyms: Malaria, susceptibility to [OMIM: 611162] Disease Ontology: DOID:14069 OMIM: 611162
Disease:  Cervical cancer Disease Ontology: DOID:4362 OMIM: 603956
Disease:  Endometrial cancer Disease Ontology: DOID:1380 OMIM: 608089
Disease:  Human immunodeficiency virus type 1, susceptibility to Synonyms: Human immunodeficiency virus infectious disease [Disease Ontology: DOID:526] Disease Ontology: DOID:526 OMIM: 609423 Orphanet: ORPHA319269
Disease:  Lupus nephritis
Disease:  Lymphoma, non-hodgkin, familial Description: A lymphoma that is characterized as any kind of lymphoma except Hodgkin's lymphoma. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and lethargy. Synonyms: Non-Hodgkin lymphoma [Disease Ontology: DOID:0060060] Disease Ontology: DOID:0060060 OMIM: 605027
Disease:  Prostate cancer Disease Ontology: DOID:10283 OMIM: 176807
Disease:  Systemic lupus erythematosus Description: SLE is a complex autoimmune disease that is characterised by inflammation of various connective tissues, and symptoms include dermatitis, arthritis, inflammation of the kidneys (glomerulonephritis), vasculitis, inflammation of the tissue surrounding the heart, and seizures. It is caused by the production of autoantibodies against widely expressed nuclear, cytoplasmic, and cell surface molecules. Extracellular RNA in the circulation in combination with the presence of autoantibodies potently stimulates interferon production and immune system activation. Disease Ontology: DOID:9074 OMIM: 152700 Orphanet: ORPHA536

General Comments
TLR9 is an intracellular detector for pathogen-derived nucleic acids, in particular CpG dinucleotides. Trafficking of endosomal TLR9 is tightly controlled to prevent inappropriate activation [2]. The potential role of TLR9 in immuno-oncology is reviewed in [1].