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	3.80.10.10, 3.40.50.10140
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)

Immuno Process:  Inflammation

Immuno Process:  Immune system development

Immuno Process:  Immune regulation

Immuno Process:  Cytokine production & signalling

Immuno Process:  Chemotaxis & migration

Immuno Process:  Cellular signalling

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].