TLR9

Toll-like receptor 9 • UniProt accession Q9NR96

Key component of innate and adaptive immunity (PubMed:14716310). TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms (PubMed:14716310). TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides (PubMed:14716310).

Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:11564765, PubMed:17932028). Also acts via ADCY7, leading to cyclic di-AMP (c-di-AMP) synthesis and activation of the NLRP3 inflammasome (By similarity). Plays a role in defense against systemic mouse cytomegalovirus infection (By similarity).

Controls lymphocyte response to Helicobacter infection (By similarity). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (PubMed:23857366)

Source: UniProt

Monomer and homodimer. Exists as a monomer in the absence of unmethylated cytidine-phosphate-guanosine (CpG) ligand. Proteolytic processing of an insertion loop (Z-loop) is required for homodimerization upon binding to the unmethylated CpG ligand leading to its activation (By similarity).

Interacts with MYD88 via their respective TIR domains (By similarity). Interacts with BTK (PubMed:17932028). Interacts (via transmembrane domain) with UNC93B1.

Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses (By similarity). Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:20865800). Interacts with SMPDL3B (By similarity).

Interacts with CD82; this interaction is essential for TLR9-dependent myddosome formation in response to CpG stimulation (By similarity). Interacts with ADCY7; leading to ADCY7 activation, synthesis of cyclic di-AMP (c-di-AMP) and formation of the NLRP3 inflammasome (By similarity)

Source: UniProt
Endoplasmic reticulum membrane — Single-pass type I membrane protein, Early endosome membrane, Lysosome, Cytoplasmic vesicle, phagosome, Golgi apparatus membrane
Source: UniProt

Highly expressed in spleen, lymph node, tonsil and peripheral blood leukocytes, especially in plasmacytoid pre-dendritic cells. Levels are much lower in monocytes and CD11c+ immature dendritic cells. Also detected in lung and liver

Source: UniProt
  • PI3K Cascade
  • Trafficking and processing of endosomal TLR
  • Toll Like Receptor 9 (TLR9) Cascade
  • Potential therapeutics for SARS
  • TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
  • TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
  • MyD88 dependent cascade initiated on endosome
Source: Reactome via UniProt

Mutations

No mutation information available.

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to TLR9, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 7

NCT ID Condition Brief Title Phase Status
NCT02927964 Grade 1 Follicular Lymphoma, Grade 2 Follicular Lymphoma, Grade 3a Follicular Lymphoma, Recurrent Follicular Lymphoma, Refractory Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma PHASE1, PHASE2 COMPLETED
NCT03618641 Melanoma, Lymph Node Cancer CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease PHASE2 COMPLETED
NCT03507699 Colorectal Neoplasms Malignant, Liver Metastases Combined Immunotherapy and Radiosurgery for Metastatic Colorectal Cancer PHASE1 COMPLETED
NCT06710223 Hepatocellular Carcinoma Cryoablation and Arterial Infusion of SD-101 in Combination With Durvalumab and Tremelimumab PHASE1 RECRUITING
NCT02898662 Asthma AZD1419 Ph2a Study PHASE2 COMPLETED
NCT04985968 Ulcerative Colitis The Efficacy and Safety of Cobitolimod in Participants With Moderate to Severe Active Left-Sided Ulcerative Colitis PHASE3 TERMINATED
NCT04270864 Advanced Cancer Intratumoral Tilsotolimod, a TLR-9 Agonist, Together With Intratumoral Ipilimumab and Intravenous Nivolumab in Patients With Advanced Cancers PHASE1 TERMINATED
NCT02087644 Asthma CYT003 in Patients With Mild to Moderate Allergic Asthma Not Sufficiently Controlled on Inhaled Glucocorticosteroids PHASE2 WITHDRAWN
NCT02452697 Myeloid Malignancies, Lymphoid Malignancies Ph2 NK Cell Enriched DCIs w/wo RLR9 Agonist, DUK-CPG-001 From Donors Following Allogeneic SCT PHASE2 UNKNOWN
NCT04401995 Melanoma Study of TLR9 Agonist Vidutolimod (CMP-001) in Combination with Nivolumab Vs. Nivolumab PHASE2 COMPLETED