Protein / target

Toll-like receptor 9

Encoded byTLR9Q9NR96Homo sapiensSwiss-Prot

UniProt: Q9NR96 Ensembl: ENSG00000239732 HGNC: HGNC:15633 NCBI Gene: 54106

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

Small-molecule tractable

Druggability

Approved Drug

Research papers

Protein at a glance

Biological role

Pattern recognition receptor

Strongest disease association

Arthritis, Rheumatoid

Via encoding gene TLR9 · Clinical evidence · score 0.62

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

6 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Key component of innate and adaptive immunity.

View complete UniProt function annotation

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, PubMed:40980882). 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)

Subcellular location

Endoplasmic reticulum membraneEarly endosome membraneLysosomeCytoplasmic vesicle, phagosomeGolgi apparatus membrane

Domains and Gene Ontology detail (61)

Domains & features

TIR

Gene Ontology

Capical plasma membrane
Cbasolateral plasma membrane
Ccytoplasm
Cearly endosome membrane
Cearly phagosome
Cendolysosome
Cendolysosome membrane
Cendoplasmic reticulum
Cendoplasmic reticulum membrane
Cendosome
Cendosome membrane
Cextracellular region

1032 aa · 116 kDa · 5 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Immune signallingUniProt · GOTranscriptional regulationGO

View supporting evidence

Immune signalling

·Key component of innate and adaptive immunity (PubMed:14716310). TLRs (Toll-like recepto…
·interleukin-1 receptor binding
·innate immune response
·positive regulation of B cell activation

Transcriptional regulation

·positive regulation of gene expression
·positive regulation of transcription by RNA polymerase II

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene TLR9

Gene-level evidence surfaced through the gene TLR9that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Arthritis, Rheumatoid

0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Malaria

0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

Lupus Erythematosus, Systemic

0.65Moderately supported

Clinical evidence dominant · Open Targets 0.51

COVID-19

0.57Moderately supported

Clinical evidence dominant · Open Targets 0.44

Cutaneous lupus erythematosus

0.54Moderately supported

Clinical evidence dominant · Open Targets 0.43

View evidence synthesis (5)

Arthritis, RheumatoidWell supported

0.77

agreement 0.61–0.92

Clinical86%Literature14%

Open Targets aggregate 0.62 · 2 independent evidence families

MalariaModerately supported

0.72

agreement 0.56–0.87

Clinical85%Literature15%

Open Targets aggregate 0.58 · 2 independent evidence families

Lupus Erythematosus, SystemicModerately supported

0.65

agreement 0.50–0.81

Clinical80%Literature20%

Open Targets aggregate 0.51 · 2 independent evidence families

COVID-19Moderately supported

0.57

agreement 0.42–0.73

Clinical82%Literature18%

Open Targets aggregate 0.44 · 2 independent evidence families

Cutaneous lupus erythematosusModerately supported

0.54

agreement 0.38–0.69

Clinical100%Literature0%

Open Targets aggregate 0.43 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Arthritis, Rheumatoid0.62

Malaria0.58

Lupus Erythematosus, Systemic0.51

COVID-190.44

Cutaneous lupus erythematosus0.43

Carcinoma, Non-Small-Cell Lung0.38

Colorectal Neoplasms0.37

Pneumonia0.37

Melanoma0.36

Sjogren's Syndrome0.36

Drug development

11 compounds recorded · 2 approved · 9 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (10)

LEFITOLIMODPhase 3

HYDROXYCHLOROQUINE SULFATEApproval

BAZLITORANPhase 2

AGATOLIMODPhase 3

EMD-1201081Phase 2

AGATOLIMOD SODIUMPhase 3

1018 ISSPhase 3

HYDROXYCHLOROQUINEApproval

TILSOTOLIMOD SODIUMPhase 2

TILSOTOLIMODPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and High-Quality Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (8)

SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.