TLR9

Summary

TLR9 (toll like receptor 9, HGNC:15633) is a protein-coding gene on chromosome 3p21.2, encoding Toll-like receptor 9 (Q9NR96). Key component of innate and adaptive immunity.

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. Studies in mice and human indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response.

Source: NCBI Gene 54106 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 144 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 16 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 8 curated mechanism-of-action drugs; 5 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 1 — Hydroxychloroquine Sulfate
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.12 (unconstrained)
• MANE Select transcript: NM_017442
• Interaction hub: 2,800 STRING partners (top 3% of genes corpus-wide)
• Notable: 144 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15633
Approved symbol	TLR9
Name	toll like receptor 9
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Aliases	CD289
Ensembl gene	ENSG00000239732
Ensembl biotype	protein_coding
OMIM	605474
Entrez	54106

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000360658

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000360658, ENST00001144037

RefSeq mRNA: 1 — MANE Select: NM_017442 NM_017442

CCDS: CCDS2848

Canonical transcript exons

ENST00000360658 — 2 exons

Exon	Start	End
ENSE00001415425	52225527	52225645
ENSE00001931961	52221080	52224312

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 76.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7463 / max 131.5319, expressed in 85 samples.

Highest expression (Bgee): blood, granulocyte, lymph node, bone marrow cell, spleen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TLR9 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	2.0e-09	-0.57	3:52409264:A:G
Brain Cerebellum	eqtl	4.9e-09	-0.71	3:52373789:T:C
Thyroid	eqtl	6.6e-04	+0.16	3:52240726:A:C
Artery Tibial	eqtl	1.8e-03	-0.52	3:52221728:C:T
Esophagus Muscularis	eqtl	2.2e-03	+0.25	3:52474390:G:A
Colon Sigmoid	eqtl	3.1e-03	-0.31	3:52195079:C:G
Skin Sun Exposed Lower leg	eqtl	7.6e-03	+0.12	3:52433247:G:A
Lung	eqtl	1.5e-02	+0.46	3:51413173:A:T
Nerve Tibial	eqtl	2.0e-02	-0.41	3:51316888:T:C
Cells Cultured fibroblasts	eqtl	2.0e-02	+0.49	3:51409179:A:T
Spleen	eqtl	2.1e-02	+1.12	3:52687222:G:T
Artery Aorta	eqtl	2.4e-02	-0.73	3:52221728:C:T
Brain Amygdala	eqtl	2.8e-02	+0.35	3:52239405:G:A
Testis	eqtl	3.0e-02	-0.14	3:52306620:GGGGCTGGATA:G
Adipose Visceral Omentum	eqtl	4.0e-02	-0.11	3:52227015:A:G
Skin Not Sun Exposed Suprapubic	eqtl	4.0e-02	+0.24	3:52434924:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
42408	0.6697	82
42407	0.0766	41

Top tissues by expression

showing 100 of 128 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	76.24	gold quality
granulocyte	CL:0000094	69.54	gold quality
lymph node	UBERON:0000029	68.21	gold quality
bone marrow cell	CL:0002092	66.24	silver quality
spleen	UBERON:0002106	64.07	gold quality
bone marrow	UBERON:0002371	64.04	gold quality
monocyte	CL:0000576	63.82	gold quality
cerebellar hemisphere	UBERON:0002245	63.44	gold quality
cerebellum	UBERON:0002037	63.35	gold quality
cerebellar cortex	UBERON:0002129	63.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	63.02	gold quality
leukocyte	CL:0000738	62.85	gold quality
gastrocnemius	UBERON:0001388	62.56	gold quality
muscle of leg	UBERON:0001383	61.58	gold quality
skeletal muscle tissue	UBERON:0001134	61.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	60.13	gold quality
vermiform appendix	UBERON:0001154	59.70	gold quality
right coronary artery	UBERON:0001625	59.62	gold quality
descending thoracic aorta	UBERON:0002345	59.57	gold quality
right ovary	UBERON:0002118	59.08	gold quality
thoracic aorta	UBERON:0001515	57.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	57.15	gold quality
ascending aorta	UBERON:0001496	57.14	gold quality
apex of heart	UBERON:0002098	56.93	gold quality
left ovary	UBERON:0002119	56.80	gold quality
muscle tissue	UBERON:0002385	56.53	gold quality
ovary	UBERON:0000992	56.39	gold quality
urinary bladder	UBERON:0001255	55.99	gold quality
endocervix	UBERON:0000458	55.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	55.83	gold quality
small intestine	UBERON:0002108	55.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	55.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	55.34	gold quality
lower esophagus	UBERON:0013473	55.28	gold quality
body of uterus	UBERON:0009853	55.21	gold quality
gall bladder	UBERON:0002110	55.18	gold quality
popliteal artery	UBERON:0002250	54.62	gold quality
tibial artery	UBERON:0007610	54.55	gold quality
mucosa of stomach	UBERON:0001199	54.22	gold quality
myometrium	UBERON:0001296	53.75	gold quality
uterine cervix	UBERON:0000002	53.62	gold quality
vagina	UBERON:0000996	52.96	gold quality
duodenum	UBERON:0002114	52.73	gold quality
fundus of stomach	UBERON:0001160	52.71	gold quality
intestine	UBERON:0000160	52.46	gold quality
omental fat pad	UBERON:0010414	52.46	gold quality
colon	UBERON:0001155	52.40	gold quality
tonsil	UBERON:0002372	52.13	gold quality
tibial nerve	UBERON:0001323	52.12	gold quality
left coronary artery	UBERON:0001626	51.98	gold quality
adipose tissue	UBERON:0001013	51.77	gold quality
ectocervix	UBERON:0012249	51.73	gold quality
subcutaneous adipose tissue	UBERON:0002190	51.62	gold quality
transverse colon	UBERON:0001157	50.99	gold quality
multicellular organism	UBERON:0000468	50.70	gold quality
esophagus	UBERON:0001043	50.33	gold quality
lower esophagus mucosa	UBERON:0035834	50.17	gold quality
thoracic mammary gland	UBERON:0005200	49.79	gold quality
prostate gland	UBERON:0002367	49.77	gold quality
heart left ventricle	UBERON:0002084	49.32	gold quality
upper lobe of left lung	UBERON:0008952	49.32	gold quality
mucosa of transverse colon	UBERON:0004991	48.48	gold quality
right uterine tube	UBERON:0001302	48.43	gold quality
right frontal lobe	UBERON:0002810	48.32	gold quality
right lung	UBERON:0002167	48.18	gold quality
placenta	UBERON:0001987	47.58	gold quality
right lobe of liver	UBERON:0001114	47.52	silver quality
right adrenal gland cortex	UBERON:0035827	47.14	gold quality
nucleus accumbens	UBERON:0001882	47.11	gold quality
fallopian tube	UBERON:0003889	47.00	gold quality
brain	UBERON:0000955	46.96	gold quality
heart	UBERON:0000948	46.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	46.66	gold quality
thyroid gland	UBERON:0002046	46.63	gold quality
right adrenal gland	UBERON:0001233	46.57	gold quality
anterior cingulate cortex	UBERON:0009835	46.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.36	gold quality
left lobe of thyroid gland	UBERON:0001120	46.33	gold quality
left uterine tube	UBERON:0001303	46.27	gold quality
esophagus mucosa	UBERON:0002469	46.04	gold quality
colonic epithelium	UBERON:0000397	45.90	gold quality
caudate nucleus	UBERON:0001873	45.85	gold quality
body of stomach	UBERON:0001161	45.78	gold quality
saliva-secreting gland	UBERON:0001044	45.55	gold quality
lung	UBERON:0002048	45.51	gold quality
left adrenal gland	UBERON:0001234	45.47	gold quality
Ammon’s horn	UBERON:0001954	45.37	gold quality
putamen	UBERON:0001874	45.01	gold quality
stomach	UBERON:0000945	44.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	44.72	gold quality
minor salivary gland	UBERON:0001830	44.67	gold quality
adrenal gland	UBERON:0002369	44.54	gold quality
amygdala	UBERON:0001876	44.53	gold quality
cerebral cortex	UBERON:0000956	44.49	gold quality
left adrenal gland cortex	UBERON:0035825	44.45	gold quality
right lobe of thyroid gland	UBERON:0001119	44.41	gold quality
skin of abdomen	UBERON:0001416	44.41	gold quality
temporal lobe	UBERON:0001871	44.32	gold quality
substantia nigra	UBERON:0002038	44.23	gold quality
right atrium auricular region	UBERON:0006631	43.87	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	13.44
E-MTAB-8498	yes	12.09
E-MTAB-9801	yes	8.19
E-ANND-3	no	1.27

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 69 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Lymph node	tissue	5.6
Corpus callosum	tissue	4.5
Spinal cord	tissue	3.9
Tonsil	tissue	3.8
Periaqueductal gray	tissue	3.8
Hypothalamus	tissue	3.7
Substantia nigra	tissue	3.6
Medulla oblongata	tissue	3.5
Septum	tissue	3.4
Midbrain	tissue	3.2
Ventral forebrain	tissue	3.2
Putamen	tissue	3.1
Amygdala	tissue	3.1
Hippocampal formation	tissue	3.1
Cerebral cortex	tissue	3.0
Basal ganglia	tissue	3.0
Olfactory bulb	tissue	3.0
Insular cortex	tissue	3.0
Retrosplenial and cingulate cortex	tissue	2.9
Pons	tissue	2.8
Thalamus	tissue	2.8
Spleen	tissue	2.8
Retrosplenial cortex	tissue	2.8
Entorhinal cortex	tissue	2.7
Temporal cortex	tissue	2.7
Cerebellum	tissue	2.6
Prefrontal cortex	tissue	2.5
Motor cortex	tissue	2.5
Superior colliculi	tissue	2.5
Appendix	tissue	2.4
Occipital cortex	tissue	2.4
Somatosensory cortex	tissue	2.1
Nucleus accumbens	tissue	1.4
Thymus	tissue	1.4
Hippocampus	tissue	1.2
Bone marrow	tissue	1.2
Postcentral gyrus	tissue	1.2
Skeletal muscle	tissue	1.1
Vagina	tissue	1.0
Locus coeruleus	tissue	1.0
Caudate putamen	tissue	0.8
Salivary gland	tissue	0.7
Choroid plexus	tissue	0.7
Frontal cortex	tissue	0.6
Gallbladder	tissue	0.6
Stomach 1	tissue	0.5
Pituitary gland	tissue	0.4
Urinary bladder	tissue	0.4
Tongue	tissue	0.4
Small intestine	tissue	0.4
Duodenum	tissue	0.4
Cervix	tissue	0.3
Heart muscle	tissue	0.3
Ovary	tissue	0.3
Adipose tissue	tissue	0.3
Colon	tissue	0.3
Lung	tissue	0.3
Skin 1	tissue	0.2
Seminal vesicle	tissue	0.2
Endometrium 1	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Area parastriata, superior (10.3), White matter (4.5), Ventral spinal cord (3.9), Flocculonodular lobe (3.8), Vermis (3.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPA, CEBPB, CEBPD, CEBPE, CREB1, ELF1, ELK1, ESR1, ETS2, HDAC3, IRF3, IRF6, JUN, NFKB1, NFKB, PTMA, RELA, STAT3

miRNA regulators (miRDB)

Targeting TLR9 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

8 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6742-5P	96.32	64.01	869

Functional genomics

gnomAD constraint: pLI 1.05e-06, LOEUF 1.12, missense Z 3.13 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000360658 — one region, missense o/e 0.77.

Literature-anchored findings (GeneRIF, showing 40)

• TLR9 acts at the cell surface and engages an intracellular signaling pathway that includes MyD88, IRAK, and TRAF6 (PMID:11867692)
• Toll-like receptor 9 functions in the activation of RF expressing B-cells. (PMID:11976718)
• In naive B cells, the expression of TLR9 and TLR10 is rapidly induced following B-cell-receptor (BCR) triggering. In contrast, memory B cells express several TLRs at constitutively high levels. (PMID:12560217)
• All nine patients expressed all of the TLRs studied, whereas only five out of the nine patients had any granulomas positive for IL-4.The associations between TLRs 1, 5, and 9 were different in IL-4-negative compared with IL-4-positive patients. (PMID:12600829)
• normal and neoplastic human B lymphocytes express a distinct TLR repertoire including TLR9 and TLR10 and expression is increased upon engagement of the antigen receptor complex or TLR9 itself (PMID:12689944)
• Costimulation with TLR9 (or TLR2) and TLR4 induces synergistic release of Th1 cytokines, IFN-gamma and TNF-alpha, and additive HIV-LTR trans-activation and HIV replication, as measured by p24 antigen release from HIV-1 transgenic mouse spleen cells. (PMID:12734363)
• A synergistic role is played by the TLR9/CD40 system in the orchestration of CpG-ODN-induced responses in B lymphocytes. (PMID:12778475)
• peptidoglycan signaling through TLR2 and bacterial CpG DNA signaling through TLR9 are functionally equivalent at synergizing with IFN-gamma in regulating Tap-1 expression in macrophages (PMID:14694183)
• mechanism of cellular activation involving the recruitment of TLR9 from the ER to sites of CpG DNA uptake, where signal transduction is initiated (PMID:14716310)
• TLR signals that activate NF-kappaB are diverse among different TLRs, and TLR9 signaling uniquely depends on IRF-8 in DCs. (PMID:15153500)
• mechanism of TLR9 gene regulation (PMID:15294971)
• Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. (PMID:15307186)
• TLR9 expression may function as a proinflammatory activation marker during the transition from monocyte to dendritic cells. (PMID:15585868)
• Moreover, the TLR9 transfectant demonstrated its usefulness for evaluation of immunostimulation by bacterial DNA through the detection of T(H)-1, T(H)-2 type cytokine induction via TLR9 signaling. (PMID:15607737)
• The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology. (PMID:15631627)
• TLR9 gene polymorphisms were not significantly associated with the susceptibility to systemic lupus erythematosus in Korean patients. (PMID:15730519)
• The TLR9 was analyzed by ICS as it was reported to be expressed in an intracellular compartment. (PMID:15790341)
• a CpR dinucleotide is recognized by TLR9 and leads immune-cell activation and cytokine secretion in vitro and in vivo (PMID:15860583)
• Diminished expression and function of TLR9 is a likely consequence of chronic filarial antigen stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in lymphatic filariasis (PMID:16002719)
• results demonstrated that TLR9 expression is correlated with immune activation and differs between individuals with non-activated or chronically immune activated background (PMID:16024265)
• Data indicate that the two TLR-9 promotor polymorphisms are not involved in atherogenesis. (PMID:16125159)
• TLR9 may have a critical role in the promotion of lupus through the induction of IFN-alpha by predendritic cells. (PMID:16230478)
• TLR9- and FcepsilonRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression. (PMID:16237063)
• Activation of TLR-9 induces IL-8 secretion through peroxynitrite signaling in neutrophils. (PMID:16394009)
• Broad TLR9 activation defects in common variable immune deficiency prevent CpG-DNA-initiated innate immune responses; these defects may lead to impaired responses of plasmacytoid dendritic cells and loss of B cell function. (PMID:16424230)
• Bacterial DNA preparations from different species differ in their capacity to activate TLR-9, which is dependent on the individual [CG] content. Moreover, increased intracellular delivery results in a marked enhancement of immunostimulation. (PMID:16428738)
• significant increase of the combined carriership of the CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group suggests that these markers identify a subgroup of patients with a risk of developing chronic or refractory pouchitis (PMID:16437636)
• we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection with live pathogens may lead to activation of PRR not targeted by inactivated bacteria. (PMID:16731773)
• TLR4 and TLR9 polymorphisms increased the risk of low birth weight in infants; polymorphisms of TLR4 increased the risk of maternal anemia. (PMID:16779724)
• findings demonstrate that TLR-3 and TLR-9 mediate the activation of corneal cells by Herpes simplex virus 1, HSV-1 DNA and HSV-1-antibody complexes (PMID:16847112)
• Toll-like receptor 9 (TLR9) recognizes microbial DNA. We show here that TLR9 protein is expressed in human breast cancer cells and clinical breast cancer samples. (PMID:16849519)
• This establishes that the primary determinant of TLR9 signaling is not valency but endosomal location and demonstrates a strict compartmentalization of the biological response to TLR9 activation in plasmacytoid dendritic cells (PDCs). (PMID:16864658)
• Plays a role of in the recognition of M. bovis BCG by dendritic cells. (PMID:16920494)
• TLR2 and TLR9 cooperate in the control of parasite replication during Trypanosoma cruzi infection; TLR9 has a primary role in the MyD88-dependent induction of IL-12/IFN-gamma synthesis during infection with T. cruzi. (PMID:16951309)
• The results of this study suggest a model where modification of the cytoplasmic tail of TLR9 results in trafficking to early endosomes where it encounters CpG DNA. (PMID:16990271)
• reviews experience with two distinct therapeutic strategies: TLR9-based immunomodulation and TLR9-based vaccination (PMID:17000223)
• TLR8 inhibits TLR7 and TLR9, and TLR9 inhibits TLR7 but not vice versa in HEK293 cells transfected with TLRs in a pairwise combination. (PMID:17040905)
• In patients with active systemic lupus erythematosus, the proportion of peripheral blood memory B cells and plasma cells expressing TLR-9 is increased (PMID:17075805)
• HMGB1 suppresses PDC cytokine secretion and maturation in response to TLR9 agonists including the hypomethylated oligodeoxynucleotide CpG- and DNA-containing viruses (PMID:17142771)
• immune cells use several mechanisms to discriminate between stimulatory and nonstimulatory DNA; however, it appears that TLR9 itself binds rather indiscriminately to a broad range of DNAs (PMID:17145922)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tlr9	ENSMUSG00000045322
rattus_norvegicus	Tlr9	ENSRNOG00000048161

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRRN3 (ENSG00000173114), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), LRRN1 (ENSG00000175928), SLITRK1 (ENSG00000178235), GP5 (ENSG00000178732), SLITRK4 (ENSG00000179542), LRRC55 (ENSG00000183908), SLIT3 (ENSG00000184347), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), SLIT1 (ENSG00000187122), TPBGL (ENSG00000261594)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1932389) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 24 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal macrophage physiology	7
decreased tumor necrosis factor secretion	4
abnormal dendritic cell physiology	2
decreased B cell proliferation	2
decreased interferon-alpha secretion	2
decreased interferon-beta secretion	2
decreased interleukin-12b secretion	2
increased susceptibility to Herpesvirales infection	2
abnormal immune system physiology	1
decreased inflammatory response	1
abnormal B cell physiology	1
abnormal cytokine secretion	1
abnormal leukocyte migration	1
decreased susceptibility to experimental autoimmune encephalomyelitis	1
abnormal response to infection	1
decreased susceptibility to parasitic infection	1
impaired natural killer cell mediated cytotoxicity	1
abnormal T-helper 1 physiology	1
abnormal NK T cell physiology	1
increased susceptibility to induced colitis	1
decreased interferon-gamma secretion	1
abnormal plasmacytoid dendritic cell physiology	1
abnormal NK cell physiology	1
increased susceptibility to Herpesvirales infection induced morbidity/mortality	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Ovis aries	O46390	99.5%	Diamond
Bos taurus	P21809	99.5%	Diamond
Macaca mulatta	B3Y618	99.2%	Diamond
Macaca fascicularis	Q95M53	99.2%	Diamond
Capra ibex	B2LT62	98.0%	Diamond
Oryctolagus cuniculus	O46378	98.0%	Diamond
Sus scrofa	Q9TTB4	98.0%	Diamond
Canis lupus familiaris	O02678	97.8%	Diamond
Pongo abelii	Q5R6T0	97.5%	Diamond
Capra hircus	Q0GC71	96.8%	Diamond
Felis catus	Q5I2M7	89.6%	Diamond
Equus caballus	Q2EEY0	86.1%	Diamond
Xenopus laevis	Q9IB75	85.9%	Diamond
Cricetulus griseus	Q9R1F8	83.9%	Diamond
Gallus gallus	P51887	70.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TWF2	protein-coding	11344
PPM1M	protein-coding	132160
MIRLET7G	ncRNA	406890
WDR82	protein-coding	80335
ALAS1	protein-coding	211
POC1A	protein-coding	25886
TWF2-DT	ncRNA	101929054
LINC00696	ncRNA	100128378

Protein

Protein identifiers

Toll-like receptor 9 — Q9NR96 (reviewed: Q9NR96)

All UniProt accessions (1): Q9NR96

UniProt curated annotations — full annotation on UniProt →

Function. Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also acts via ADCY7, leading to cyclic di-AMP (c-di-AMP) synthesis and activation of the NLRP3 inflammasome. Plays a role in defense against systemic mouse cytomegalovirus infection. Controls lymphocyte response to Helicobacter infection. Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production.

Subunit / interactions. 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. Interacts with MYD88 via their respective TIR domains. Interacts with BTK. Interacts (via transmembrane domain) with UNC93B1. Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses. Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum. Interacts with SMPDL3B. Interacts with CD82; this interaction is essential for TLR9-dependent myddosome formation in response to CpG stimulation. Interacts with ADCY7; leading to ADCY7 activation, synthesis of cyclic di-AMP (c-di-AMP) and formation of the NLRP3 inflammasome.

Subcellular location. Endoplasmic reticulum membrane. Early endosome membrane. Lysosome. Cytoplasmic vesicle. Phagosome. Golgi apparatus membrane.

Tissue specificity. 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.

Post-translational modifications. Activated by proteolytic cleavage of the flexible loop between repeats LRR14 and LRR15 within the ectodomain. Cleavage requires UNC93B1. Proteolytically processed by first removing the majority of the ectodomain by either asparagine endopeptidase (AEP) or a cathepsin followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling. Phosphorylation of Tyr-870 by SYK and Tyr-980 by EGFR is essential for TLR9-mediated gene induction. Palmitoylated by ZDHHC3 in the Golgi regulates TLR9 trafficking from the Golgi to endosomes. Depalmitoylation by PPT1 controls the release of TLR9 from UNC93B1 in endosomes.

Similarity. Belongs to the Toll-like receptor family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9NR96-1	1, A	yes
Q9NR96-2	2, B
Q9NR96-3	3
Q9NR96-4	4
Q9NR96-5	5

RefSeq proteins (1): NP_059138* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000157	TIR_dom	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR035897	Toll_tir_struct_dom_sf	Homologous_superfamily
IPR041283	LRR_12	Repeat

Pfam: PF01582, PF13516, PF13855, PF18837

UniProt features (83 total): repeat 26, glycosylation site 13, disulfide bond 8, binding site 6, sequence variant 6, splice variant 4, sequence conflict 4, topological domain 2, modified residue 2, lipid moiety-binding region 2, mutagenesis site 2, helix 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, turn 1, strand 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
9L48	Crystal structure of HLA-C*12:02-RV9	X-RAY DIFFRACTION	1.9
9L49	Crystal structure of HLA-C*12:03-RV9	X-RAY DIFFRACTION	3
8AR3	Solution structure of TLR9 transmembrane and cytoplasmic juxtamembrane regions	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR96-F1	86.96	0.65

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6)

Position	Role
47–51	DNA
72–77	DNA
95–109	DNA
132	DNA
179–181	DNA
208	DNA

Post-translational modifications (4)

Type	Positions
Phosphotyrosine	870, 980
S-palmitoyl cysteine	258, 265

Disulfide bonds (8)

Type	Positions
Disulfide bond	35–45, 98–110, 178–184, 255–268, 258–265, 470–500, 764–790, 766–809

Glycosylation sites (13)

Type	Positions
N-linked (glcnac…) asparagine	64, 129, 200, 210, 242, 300, 340, 469, 474, 513, 567, 694, 731

Mutagenesis-validated functional residues (2)

Position	Phenotype
870	significant inhibition of tlr9-induced il1b, il6, tnfaip3, and ifnb1 levels in cpg-treated cells.
980	significant inhibition of tlr9-induced il1b, il6, tnfaip3, and ifnb1 levels in cpg-treated cells.

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 23; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

23 pathways:

ID	Pathway	Evidence
R-HSA-9679191	Potential therapeutics for SARS ⚕	curated
R-HSA-975155	MyD88 dependent cascade initiated on endosome	curated
R-HSA-109704	PI3K Cascade	curated
R-HSA-975110	TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	curated
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	curated
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade	curated
R-HSA-1679131	Trafficking and processing of endosomal TLR	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-2428924	IGF1R signaling cascade	—
R-HSA-112399	IRS-mediated signalling	—
R-HSA-2428928	IRS-related events triggered by IGF1R	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-74751	Insulin receptor signalling cascade	—
R-HSA-162582	Signal Transduction	—
R-HSA-74752	Signaling by Insulin receptor	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-2404192	Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	—
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade	—
R-HSA-168898	Toll-like Receptor Cascades	—

MSigDB gene sets: 323 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_DIGESTION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION

GO Biological Process (50): microglial cell activation (GO:0001774), toll-like receptor signaling pathway (GO:0002224), positive regulation of immunoglobulin production (GO:0002639), MyD88-dependent toll-like receptor signaling pathway (GO:0002755), canonical NF-kappaB signal transduction (GO:0007249), male gonad development (GO:0008584), positive regulation of autophagy (GO:0010508), positive regulation of gene expression (GO:0010628), maintenance of gastrointestinal epithelium (GO:0030277), positive regulation of B cell proliferation (GO:0030890), detection of molecule of bacterial origin (GO:0032490), positive regulation of chemokine production (GO:0032722), positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725), positive regulation of interferon-alpha production (GO:0032727), positive regulation of interferon-beta production (GO:0032728), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-18 production (GO:0032741), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), toll-like receptor 9 signaling pathway (GO:0034162), positive regulation of toll-like receptor 9 signaling pathway (GO:0034165), defense response to bacterium (GO:0042742), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAPK cascade (GO:0043410), innate immune response (GO:0045087), regulation of B cell differentiation (GO:0045577), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330), positive regulation of inflammatory response (GO:0050729), defense response to Gram-negative bacterium (GO:0050829), positive regulation of B cell activation (GO:0050871), defense response to virus (GO:0051607), cellular response to lipopolysaccharide (GO:0071222), cellular response to metal ion (GO:0071248), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), negative regulation of ATPase-coupled calcium transmembrane transporter activity (GO:1901895), positive regulation of intestinal epithelial cell development (GO:1905300), positive regulation of cytokine production (GO:0001819), activation of innate immune response (GO:0002218), immune system process (GO:0002376), defense response (GO:0006952), inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), regulation of inflammatory response (GO:0050727), response to other organism (GO:0051707), endolysosomal toll-like receptor signaling pathway (GO:0140894)

GO Molecular Function (6): interleukin-1 receptor binding (GO:0005149), siRNA binding (GO:0035197), pattern recognition receptor activity (GO:0038187), protein homodimerization activity (GO:0042803), unmethylated CpG binding (GO:0045322), protein binding (GO:0005515)

GO Cellular Component (17): Golgi membrane (GO:0000139), extracellular region (GO:0005576), cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), endosome membrane (GO:0010008), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), early endosome membrane (GO:0031901), early phagosome (GO:0032009), endolysosome (GO:0036019), endolysosome membrane (GO:0036020), cytoplasmic vesicle (GO:0031410), phagocytic vesicle (GO:0045335)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Toll-like Receptor Cascades	3
MyD88 dependent cascade initiated on endosome	2
Signaling by Receptor Tyrosine Kinases	2
IRS-mediated signalling	1
SARS-CoV Infections	1
Toll Like Receptor 9 (TLR9) Cascade	1
Toll Like Receptor 7/8 (TLR7/8) Cascade	1
IRS-related events triggered by IGF1R	1
Insulin receptor signalling cascade	1
Immune System	1
Innate Immune System	1
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	1
IGF1R signaling cascade	1
Disease	1
Signaling by Insulin receptor	1

GO top-level categories

showing 60 of 82 GO namespaces:

Category	Terms
positive regulation of cytokine production	7
positive regulation of type I interferon production	2
bounding membrane of organelle	2
cellular anatomical structure	2
endomembrane system	2
cytoplasm	2
endosome	2
plasma membrane region	2
endosome membrane	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
glial cell activation	1
pattern recognition receptor signaling pathway	1
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
toll-like receptor signaling pathway	1
intracellular signaling cassette	1
gonad development	1
development of primary male sexual characteristics	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
epithelial structure maintenance	1
digestive system process	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
response to molecule of bacterial origin	1
detection of chemical stimulus	1
detection of external biotic stimulus	1
chemokine production	1
regulation of chemokine production	1
granulocyte macrophage colony-stimulating factor production	1
regulation of granulocyte macrophage colony-stimulating factor production	1
positive regulation of protein metabolic process	1
interferon-alpha production	1
regulation of interferon-alpha production	1
interferon-beta production	1
regulation of interferon-beta production	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-18 production	1
regulation of interleukin-18 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
cytokine receptor binding	1
growth factor receptor binding	1
regulatory RNA binding	1
signaling receptor activity	1
identical protein binding	1
protein dimerization activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 30 of 73 annotations. The rest are phylogenetic / computational / electronic (IEA).

30 experimentally-supported GO terms:

GO term	NS	Evidence
defense response to Gram-negative bacterium	BP	mutant phenotype
detection of molecule of bacterial origin	BP	direct assay
negative regulation of ATPase-coupled calcium transmembrane transporter activity	BP	direct assay
positive regulation of B cell activation	BP	direct assay
positive regulation of B cell proliferation	BP	direct assay
positive regulation of JNK cascade	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of canonical NF-kappaB signal transduction	BP	direct assay
positive regulation of chemokine production	BP	direct assay
positive regulation of gene expression	BP	direct assay
positive regulation of granulocyte macrophage colony-stimulating factor production	BP	direct assay
positive regulation of immunoglobulin production	BP	direct assay
positive regulation of inflammatory response	BP	direct assay
positive regulation of interferon-alpha production	BP	direct assay
positive regulation of interferon-beta production	BP	direct assay
positive regulation of interleukin-6 production	BP	direct assay
positive regulation of interleukin-8 production	BP	direct assay
positive regulation of type II interferon production	BP	direct assay
regulation of B cell differentiation	BP	direct assay
toll-like receptor 9 signaling pathway	BP	direct assay
toll-like receptor signaling pathway	BP	direct assay
apical plasma membrane	CC	direct assay
basolateral plasma membrane	CC	direct assay
cytoplasm	CC	direct assay
early endosome membrane	CC	direct assay
endoplasmic reticulum	CC	direct assay
plasma membrane	CC	direct assay
interleukin-1 receptor binding	MF	physical interaction
pattern recognition receptor activity	MF	direct assay
siRNA binding	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 2,800 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLR9	MYD88	P78397	960
TLR9	IRF3	Q14653	888
TLR9	IRF7	Q92985	887
TLR9	TNF	P01375	881
TLR9	IL6	P05231	881
TLR9	IFNG	P01579	878
TLR9	IL1B	P01584	876
TLR9	IFNA13	P01562	872
TLR9	IFNB1	P01574	864
TLR9	RIGI	O95786	851
TLR9	IRAK1	P51617	849
TLR9	IL10	P22301	848
TLR9	CD4	P01730	844
TLR9	CD8A	P01732	833
TLR9	IRAK4	Q9NWZ3	833

IntAct

Human interaction partners of TLR9 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
NCK1	physical association	0.400	1
RBMX	physical association	0.400	1
SIGLEC5	physical association	0.400	1
SIGLEC6	physical association	0.400	1
SIGLEC9	physical association	0.400	1
TLR8	physical association	0.400	1
ABCD4	association	0.350	1
CLGN	association	0.350	1

BioGRID (71 interactions; top human partners by supporting records): MYD88 (Two-hybrid; 2 records), RNF216 (Two-hybrid; 2 records), TNFAIP3 (Affinity Capture-MS; 2 records), ABCB9 (Affinity Capture-MS), ABCD4 (Affinity Capture-MS), ACTG1 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), BSCL2 (Affinity Capture-MS), BTK (Two-hybrid), CLGN (Affinity Capture-MS), CNPY3 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), FAM69A (Affinity Capture-MS), GSK3A (Affinity Capture-MS), GSK3B (Affinity Capture-MS)

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
BGLF5	“down-regulates quantity by destabilization”	TLR9	“post transcriptional regulation”
LMP1	“down-regulates quantity by repression”	TLR9	“transcriptional regulation”
RNF216	“down-regulates quantity by destabilization”	TLR9	ubiquitination
TLR9	“up-regulates activity”	MYD88	binding
TLR9	“up-regulates activity”	TIRAP	binding
TLR9	“up-regulates activity”	TICAM1	binding
TLR9	“up-regulates activity”	TICAM2	binding

Disease & clinical

Genetic variants

Variant evidence for TLR9: 144 ClinVar records (1 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 15 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

144 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	115
Likely benign	17
Benign	9

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
916573	NM_017442.4(TLR9):c.548C>G (p.Pro183Arg)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore TLR9’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 44):

Position(s)	Effect	Δscore	Sites
3:52224313–52224314	acceptor_loss	0.9900	6
3:52225525–52225526	donor_loss	0.9900	5
3:52225525	donor_loss	0.9600
3:52225498	donor_gain	0.9400
3:52224315	acceptor_loss	0.8900
3:52224273	acceptor_gain	0.6100
3:52225514	donor_gain	0.6100
3:52224321	acceptor_gain	0.5700
3:52224292	acceptor_gain	0.5000
3:52224274	acceptor_gain	0.4500

AlphaMissense

1,737 missense substitutions predicted likely pathogenic (of 6,741 scored), across 475 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N97	8	0.954	0.995
N318	8	0.952	0.992
N482	8	0.946	0.988
N401	8	0.938	0.991
D964	8	0.919	0.973
N425	8	0.918	0.983
N687	8	0.908	0.975
N735	8	0.906	0.982
N760	8	0.901	0.984
N638	8	0.894	0.948
F376	8	0.893	0.969
N177	8	0.892	0.986
N254	8	0.892	0.990
D912	8	0.890	0.939
F624	8	0.887	0.931
F517	8	0.884	0.959
F935	8	0.877	0.970
F541	8	0.875	0.943
N608	8	0.874	0.963
F119	8	0.873	0.971

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:605474 | disease phenotypes: MIM:189960

GenCC curated gene-disease

Mondo (1): esophageal atresia/tracheoesophageal fistula (MONDO:0008586)

Orphanet (1): Esophageal atresia (Orphanet:1199)

GWAS associations

15 associations:

Study	Trait	p-value
GCST90020029_779	Waist circumference adjusted for body mass index	2e-14
GCST90020027_1138	Waist-hip index	3e-14
GCST90020025_1719	Waist-to-hip ratio adjusted for BMI	1e-13
GCST90020024_354	A body shape index	2e-12
GCST004521_274	Autism spectrum disorder or schizophrenia	3e-12
GCST006269_132	General cognitive ability	1e-9
GCST006948_58	Feeling nervous	2e-9
GCST012226_166	Waist circumference adjusted for body mass index	2e-9
GCST012228_362	Waist-hip index	7e-9
GCST002149_14	Schizophrenia	1e-8
GCST012203_2	Colon cancer	1e-8
GCST004902_20	Parkinson’s disease	3e-8
GCST004521_77	Autism spectrum disorder or schizophrenia	4e-8
GCST012205_2	Distal colorectal cancer	5e-7
GCST001241_15	Bipolar disorder	2e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009597	feeling nervous measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C531835	Esophageal atresia with or without tracheoesophageal fistula *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111471 (PROTEIN FAMILY), CHEMBL4106182 (PROTEIN FAMILY), CHEMBL5804 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the TLR9 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

8 curated-mechanism drugs:

Drug	Modality	Max phase
HYDROXYCHLOROQUINE SULFATE	Small molecule	4
1018 ISS	Unknown	3
AGATOLIMOD SODIUM	Oligonucleotide	3
COBITOLIMOD	Oligonucleotide	3
TILSOTOLIMOD	Unknown	3
BAZLITORAN	Unknown	2
EMD-1201081	Unknown	2
LEFITOLIMOD	Unknown	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 138,547 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1535	HYDROXYCHLOROQUINE	4	43,272
CHEMBL140	CURCUMIN	3	95,185
CHEMBL508338	THIMEROSAL	3
CHEMBL4650329	AFIMETORAN	2	60
CHEMBL5417170	MHV-370	2	30

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs352139	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Crohn Disease;Inflammatory Bowel Diseases
rs352139	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Psoriasis

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs352139	TLR9	3	3.50	2	Tumor necrosis factor alpha (TNF-alpha) inhibitors

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

3 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs352139	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Efficacy	Genotype TT is associated with decreased response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Crohn Disease or Inflammatory Bowel Diseases as compared to genotypes CC + CT.	PMID:24776844
rs352139	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Efficacy	Genotypes CT + TT is associated with increased response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Psoriasis as compared to genotype CC.	PMID:28696418
rs352139	adalimumab, etanercept, infliximab, Tumor necrosis factor alpha (TNF-alpha) inhibitors	Efficacy	Genotypes CT + TT is associated with increased response to adalimumab, etanercept, infliximab or Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid as compared to genotype CC.	PMID:34635730

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Toll-like receptor family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 41 [PMID: 42484069]	Antagonist	7.14	pIC50
hydroxychloroquine	Antagonist	7.1	pIC50

Binding affinities (BindingDB)

4142 measured of 4195 human assays (4377 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-[5-[(2R)-2,4-dimethylpiperazin-1-yl]-4-fluoro-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-2-yl]-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.05 nM	US-11912703: 6-azaindole compounds
N-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexyl]oxolan-3-amine	IC50	0.08 nM	US-10544143: 4-azaindole compounds
N-[3-methoxy-5-[6-methyl-5-[4-(oxolan-3-ylamino)cyclohexyl]-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl]-3H-pyridin-2-ylidene]methanimidamide	IC50	0.08 nM	US-11053244: 4-azaindole compounds
2-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexyl]-6-oxa-2-azaspiro[3.4]octane	IC50	0.09 nM	US-10544143: 4-azaindole compounds
3-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]pentane-1,5-diol	IC50	0.1 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
4-[6-fluoro-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-N-[(3-methyloxetan-3-yl)methyl]cyclohexan-1-amine	IC50	0.12 nM	US-10544143: 4-azaindole compounds
6-[5-[4-(azetidin-1-yl)cyclohexyl]-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl]-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.13 nM	US-10544143: 4-azaindole compounds
N-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexyl]-N-methyloxetan-3-amine	IC50	0.14 nM	US-10544143: 4-azaindole compounds
N-[4-[4-fluoro-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-5-yl]cyclohexyl]-3-methyloxetan-3-amine	IC50	0.15 nM	US-11912703: 6-azaindole compounds
8-methoxy-6-[3-propan-2-yl-5-(4-pyrrolidin-1-ylcyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.16 nM	US-10730877: 4-Azaindole compounds
8-methoxy-6-[3-propan-2-yl-5-(4-pyrrolidin-1-ylcyclohexyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.16 nM	US-10544143: 4-azaindole compounds
N-[4-[4-fluoro-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-5-yl]cyclohexyl]oxetan-3-amine	IC50	0.16 nM	US-11912703: 6-azaindole compounds
4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexan-1-amine	IC50	0.17 nM	US-10544143: 4-azaindole compounds
6-[5-[4-(3,3-dimethylazetidin-1-yl)cyclohexyl]-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl]-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.17 nM	US-10544143: 4-azaindole compounds
8-methyl-6-(6-methyl-5-piperidin-4-yl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.18 nM	US-10544143: 4-azaindole compounds
N-[4-[4-fluoro-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-5-yl]cyclohexyl]oxan-4-amine	IC50	0.18 nM	US-11912703: 6-azaindole compounds
6-[4-[6-fluoro-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexyl]-2-oxa-6-azaspiro[3.3]heptane	IC50	0.19 nM	US-10544143: 4-azaindole compounds
2-(dimethylamino)-1-[(3R)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-3-methylpiperazin-1-yl]ethanone	IC50	0.19 nM	US-10544143: 4-azaindole compounds
2-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-1-pyrrolidin-1-ylethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-chloro-7-methyl-6-(5-piperidin-4-yl-3-propan-2-yl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-methylpropan-2-ol	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-methoxy-6-[5-[1-(2-methylsulfonylethyl)piperidin-4-yl]-3-propan-2-yl-1H-indol-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[4-[2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-N-methylacetamide	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
3-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]propan-1-ol	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-(dimethylamino)-1-[4-[3-propan-2-yl-2-[8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-1H-indol-5-yl]piperidin-1-yl]ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-(dimethylamino)ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-(methylamino)ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[cyclopropyl(2-hydroxyethyl)amino]-1-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-[methyl(propan-2-yl)amino]ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-(3,3-difluoroazetidin-1-yl)-2-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[[3-[4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-3-oxopropyl]amino]acetamide	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
US10478424, Example 253	IC50	0.2 nM	US-10478424: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
3-[[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexyl]-methylamino]propanenitrile	IC50	0.2 nM	US-10544143: 4-azaindole compounds
N-ethyl-4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-N-methylcyclohexan-1-amine	IC50	0.21 nM	US-10544143: 4-azaindole compounds
N-[4-[6-fluoro-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexyl]oxetan-3-amine	IC50	0.21 nM	US-10544143: 4-azaindole compounds
8-methyl-6-(5-piperidin-4-yl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.22 nM	US-10544143: 4-azaindole compounds
N-[4-[4-fluoro-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-5-yl]cyclohexyl]-3-methyloxetan-3-amine	IC50	0.22 nM	US-11912703: 6-azaindole compounds
6-[5-[4-(azetidin-1-yl)piperidin-1-yl]-4-fluoro-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-2-yl]-8-methyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.23 nM	US-11912703: 6-azaindole compounds
2-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]piperidin-1-yl]-N,N-dimethylacetamide	IC50	0.24 nM	US-10544143: 4-azaindole compounds
N-ethyl-N-methyl-1-[4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-5-yl]piperidin-4-amine	IC50	0.24 nM	US-11912703: 6-azaindole compounds
4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-5-yl]-N-ethyl-N-methylcyclohexan-1-amine	IC50	0.24 nM	US-11912703: 6-azaindole compounds
8-methoxy-6-[6-methyl-5-[1-(oxan-4-yl)piperidin-4-yl]-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.25 nM	US-10544143: 4-azaindole compounds
4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-N-[(3-methyloxetan-3-yl)methyl]cyclohexan-1-amine	IC50	0.26 nM	US-10544143: 4-azaindole compounds
N-ethyl-1-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-3-propan-2-yl-1H-pyrrolo[2,3-c]pyridin-5-yl]-N-methylpiperidin-4-amine	IC50	0.26 nM	US-11912703: 6-azaindole compounds
4-[6-fluoro-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-N-methylcyclohexan-1-amine	IC50	0.27 nM	US-10544143: 4-azaindole compounds
2-methyl-1-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]piperidin-1-yl]propan-2-ol	IC50	0.27 nM	US-10544143: 4-azaindole compounds
1-[(2R,5S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]-3-(1-oxa-6-azaspiro[3.3]heptan-6-yl)propan-1-one	IC50	0.27 nM	US-10544143: 4-azaindole compounds
6-[5-[(2S,5S)-2,5-dimethylpiperazin-1-yl]-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl]-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.27 nM	US-10544143: 4-azaindole compounds
4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-N,N-dimethylcyclohexan-1-amine	IC50	0.28 nM	US-10544143: 4-azaindole compounds
4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-N,N-dimethylcyclohexan-1-amine	IC50	0.28 nM	US-10730877: 4-Azaindole compounds

ChEMBL bioactivities

5540 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.46	IC50	3.5	nM	CHEMBL3356618
8.41	IC50	3.9	nM	CHEMBL3357062
8.34	IC50	4.6	nM	CHEMBL2144205
8.30	IC50	5	nM	CHEMBL5169681
8.15	IC50	7	nM	CHEMBL5094930
8.07	IC50	8.6	nM	CHEMBL3357064
7.96	IC50	11	nM	CHEMBL3357065
7.96	IC50	11	nM	CHEMBL3356617
7.96	IC50	11	nM	CHEMBL4065452
7.89	IC50	13	nM	CHEMBL3357070
7.89	IC50	13	nM	CHEMBL6134015
7.82	IC50	15	nM	CHEMBL4065452
7.82	IC50	15	nM	CHEMBL5176310
7.82	IC50	15	nM	CHEMBL6108908
7.80	IC50	16	nM	CHEMBL3356616
7.80	IC50	16	nM	CHEMBL5855721
7.80	IC50	16	nM	CHEMBL6083133
7.77	IC50	17	nM	CHEMBL5177422
7.77	IC50	17	nM	CHEMBL6083131
7.72	IC50	19	nM	CHEMBL5193639
7.72	IC50	19	nM	CHEMBL5845501
7.70	IC50	20	nM	CHEMBL3356615
7.70	IC50	20	nM	CHEMBL4278635
7.70	IC50	20	nM	CHEMBL4276673
7.70	IC50	20	nM	CHEMBL4279467
7.70	IC50	20	nM	CHEMBL4282131
7.70	IC50	20	nM	CHEMBL457704
7.70	IC50	20	nM	CHEMBL6074579
7.70	IC50	20	nM	CHEMBL6078096
7.64	IC50	23	nM	CHEMBL5857884
7.60	IC50	25	nM	CHEMBL3905103
7.57	IC50	27	nM	CHEMBL3356611
7.55	IC50	28	nM	CHEMBL3357069
7.55	IC50	28	nM	CHEMBL5187807
7.55	IC50	28	nM	CHEMBL5183377
7.52	IC50	30	nM	CHEMBL4290314
7.52	IC50	30	nM	CHEMBL4279648
7.52	IC50	30	nM	CHEMBL4281194
7.52	IC50	30	nM	CHEMBL4278682
7.52	IC50	30	nM	CHEMBL4286933
7.52	IC50	30	nM	CHEMBL515364
7.50	IC50	32	nM	CHEMBL5092293
7.50	IC50	32	nM	CHEMBL5075053
7.50	IC50	32	nM	CHEMBL6052992
7.46	IC50	35	nM	CHEMBL3356614
7.46	IC50	35	nM	CHEMBL5197857
7.46	IC50	35	nM	CHEMBL5992876
7.43	IC50	37	nM	CHEMBL4082132
7.43	IC50	37	nM	CHEMBL5974999
7.42	IC50	38	nM	CHEMBL5175416

PubChem BioAssay actives

271 with measured affinity, of 742 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-2-[4-(4-methylpiperazin-1-yl)phenyl]-7-(3-pyrrolidin-1-ylpropyl)-5,6-dihydropyrrolo[2,3-d]pyrimidine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0035	uM
2-[4-(4-methylpiperazin-1-yl)phenyl]-7-(3-pyrrolidin-1-ylpropyl)-5,6-dihydropyrrolo[2,3-d]pyrimidine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0039	uM
6,7-dimethoxy-2-[4-(4-methylpiperazin-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)quinazolin-4-amine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0046	uM
N-[6-(4-cyclopentylpiperazin-1-yl)-9-(3-pyrrolidin-1-ylpropyl)purin-2-yl]-4-(methylaminomethyl)benzamide	1846684: Antagonist activity at TLR9 (unknown origin)	ic50	0.0050	uM
6-(4-cyclopentylpiperazin-1-yl)-N-[[4-[(dimethylamino)methyl]phenyl]methyl]-9-(3-pyrrolidin-1-ylpropyl)purin-2-amine	1814740: Antagonist activity at human TLR9 expressed in HEK-blue-HTLR7 cells assessed as inhibition of CpGB-induced NFkappaB activation measured after overnight incubation by SEAP-based spectrophotometry assay	ic50	0.0070	uM
4-[3-[2-[4-(4-methylpiperazin-1-yl)phenyl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]propyl]morpholine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0086	uM
6-(3-pyrrolidin-1-ylpropoxy)-2-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]-1,3-benzoxazole	1924741: Antagonist activity at human TLR9 expressed in HEK293 cells coexpressing firefly luciferase assessed as inhibition of CpGB-induced NFkappaB activation preincubated for 30 mins followed by Oligo CpG stimulation by Steady-Glo luciferase assay	ic50	0.0110	uM
4-[4-[2-[4-(4-methylpiperazin-1-yl)phenyl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]butyl]morpholine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0110	uM
4-methyl-2-[4-(4-methylpiperazin-1-yl)phenyl]-7-(2-pyrrolidin-1-ylethyl)-5,6-dihydropyrrolo[2,3-d]pyrimidine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0110	uM
N-(4,6-dimethyl-2-pyridinyl)-2-(1,1-dioxothian-4-yl)-1-methyl-6-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]benzimidazol-4-amine	2205792: Inhibition of TLR9 in HEK-Blue hTLR9 cells preincubated with compound for 60 mins followed by ODN2006 addition and measured after 22 hrs by inducible SEAP reporter gene based assay	ic50	0.0130	uM
2-[4-[4-[7-(3-morpholin-4-ylpropyl)-5,6-dihydropyrrolo[2,3-d]pyrimidin-2-yl]phenyl]piperazin-1-yl]ethanol	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0130	uM
2-(2,4-dimethoxyphenyl)-7-(4-propan-2-ylpiperazin-1-yl)-3-(pyrrolidin-1-ylmethyl)imidazo[1,2-a]pyridine	1874521: Antagonist activity at human TLR9 expressed in HEK-blue hTLR9 cells assessed as inhibition of CpGB-induced NFkappaB activation preincubated with compound for 1 hrs followed by CpGB addition and measured next day by SEAP-based spectrophotometry assay	ic50	0.0150	uM
N-(4,6-dimethyl-2-pyridinyl)-1-methyl-2-(4-methylsulfonylphenyl)-6-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]benzimidazol-4-amine	2205792: Inhibition of TLR9 in HEK-Blue hTLR9 cells preincubated with compound for 60 mins followed by ODN2006 addition and measured after 22 hrs by inducible SEAP reporter gene based assay	ic50	0.0150	uM
1-methyl-2-(4-methylsulfonylphenyl)-N-(6-morpholin-4-ylpyridazin-3-yl)-6-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]benzimidazol-4-amine	2205792: Inhibition of TLR9 in HEK-Blue hTLR9 cells preincubated with compound for 60 mins followed by ODN2006 addition and measured after 22 hrs by inducible SEAP reporter gene based assay	ic50	0.0160	uM
4-[3-[4-methyl-2-[4-(4-methylpiperazin-1-yl)phenyl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]propyl]morpholine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0160	uM
7-(4-cyclopentylpiperazin-1-yl)-2-[4-methoxy-2-(3-pyrrolidin-1-ylpropoxy)phenyl]imidazo[1,2-a]pyridine	1874521: Antagonist activity at human TLR9 expressed in HEK-blue hTLR9 cells assessed as inhibition of CpGB-induced NFkappaB activation preincubated with compound for 1 hrs followed by CpGB addition and measured next day by SEAP-based spectrophotometry assay	ic50	0.0170	uM
2-cyclopropyl-N-(4,6-dimethyl-2-pyridinyl)-1-methyl-6-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]benzimidazol-4-amine	2205792: Inhibition of TLR9 in HEK-Blue hTLR9 cells preincubated with compound for 60 mins followed by ODN2006 addition and measured after 22 hrs by inducible SEAP reporter gene based assay	ic50	0.0170	uM
2-(2,4-dimethoxyphenyl)-N-(3-pyrrolidin-1-ylpropyl)imidazo[1,2-a]pyridin-7-amine	1874521: Antagonist activity at human TLR9 expressed in HEK-blue hTLR9 cells assessed as inhibition of CpGB-induced NFkappaB activation preincubated with compound for 1 hrs followed by CpGB addition and measured next day by SEAP-based spectrophotometry assay	ic50	0.0190	uM
2-[4-(4-methylpiperazin-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)quinazolin-4-amine	1924740: Antagonist activity at human TLR9 expressed in HEK-Blue hTLR9 cells assessed as activation of NFkappaB incubated for 16 hrs by luciferase reporter gene assay	ic50	0.0200	uM
4-(4-cyclopentylpiperazin-1-yl)-6-methoxy-2-(4-methylpiperazin-1-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0200	uM
6-methoxy-N,N-dimethyl-4-piperazin-1-yl-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-amine	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0200	uM
[4-[2-(dimethylamino)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]piperazin-1-yl]-phenylmethanone	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0200	uM
4-(4-cyclopentylpiperazin-1-yl)-6-methoxy-N,N-dimethyl-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-amine	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0200	uM
1-methyl-N-[[4-(morpholin-4-ylmethyl)phenyl]methyl]-2-(oxetan-3-yl)-6-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]benzimidazol-4-amine	2205792: Inhibition of TLR9 in HEK-Blue hTLR9 cells preincubated with compound for 60 mins followed by ODN2006 addition and measured after 22 hrs by inducible SEAP reporter gene based assay	ic50	0.0200	uM
N-(4,6-dimethyl-2-pyridinyl)-1,2-dimethyl-6-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]benzimidazol-4-amine	2205792: Inhibition of TLR9 in HEK-Blue hTLR9 cells preincubated with compound for 60 mins followed by ODN2006 addition and measured after 22 hrs by inducible SEAP reporter gene based assay	ic50	0.0200	uM
4-[2-[4-methyl-2-[4-(4-methylpiperazin-1-yl)phenyl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]ethyl]morpholine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0200	uM
2-[4-(4-methylpiperazin-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)-5,6,7,8-tetrahydroquinazolin-4-amine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0270	uM
4-[3-[2-[7-(4-cyclopentylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]-5-methoxyphenoxy]propyl]morpholine	1874521: Antagonist activity at human TLR9 expressed in HEK-blue hTLR9 cells assessed as inhibition of CpGB-induced NFkappaB activation preincubated with compound for 1 hrs followed by CpGB addition and measured next day by SEAP-based spectrophotometry assay	ic50	0.0280	uM
2-(2,4-dimethoxyphenyl)-7-(4-propan-2-ylpiperazin-1-yl)imidazo[1,2-a]pyridine	1874527: Antagonist activity at TLR9 in human pDCs inhibition of CpGB-induced NFkappaB activation by measuring IFN-alpha levels preincubated with compound for 1 hrs followed by CpGB addition and measured after 18 hrs by ELISA analysis	ic50	0.0280	uM
4-[3-[2-[4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]propyl]morpholine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0280	uM
4-[4-(cyclopentylmethyl)piperazin-1-yl]-6-methoxy-N,N-dimethyl-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-amine	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0300	uM
4-(4-cyclopentylpiperazin-1-yl)-6-methoxy-N-[3-(4-methylpiperazin-1-yl)propyl]-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-amine	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0300	uM
[4-(aminomethyl)phenyl]-[4-[2-(dimethylamino)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]piperazin-1-yl]methanone	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0300	uM
[4-[2-(dimethylamino)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]piperazin-1-yl]-(4-fluorophenyl)methanone	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0300	uM
6-methoxy-4-(4-methylpiperazin-1-yl)-N-[3-(4-methylpiperazin-1-yl)propyl]-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-amine	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0300	uM
N’,N’-dimethyl-N-[2-[4-(4-methylpiperazin-1-yl)phenyl]quinazolin-4-yl]ethane-1,2-diamine	389404: Antagonist activity at human TLR9 expressed in HEK293 cells assessed as blockade of CpG oligonucleotide-induced immune response by NF-kappaB luciferase reporter gene assay	ic50	0.0300	uM
5-[(4R,10bS)-8-(3a-methoxy-1,2,3,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile	1846687: Antagonist activity at R848 stimulated TRL9 in HEK-Blue hTLR9 cells assessed as inhibition of NF kappa B/Ap-1 activation measured after 20 hrs by SEAP reporter assay	ic50	0.0320	uM
5-[(2S,6R)-2-[[8-(2,6-dimethyl-4-pyridinyl)-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl]methyl]-6-methylmorpholin-4-yl]quinoline-8-carbonitrile	1846687: Antagonist activity at R848 stimulated TRL9 in HEK-Blue hTLR9 cells assessed as inhibition of NF kappa B/Ap-1 activation measured after 20 hrs by SEAP reporter assay	ic50	0.0320	uM
2-deuterio-5-[(2R,6S)-2-methyl-6-[[6-(5-oxa-2,8-diazaspiro[3.5]nonan-2-yl)spiro[1H-2-benzofuran-3,3’-azetidine]-1’-yl]methyl]morpholin-4-yl]quinoline-8-carbonitrile	1817772: Inhibition of human TLR9 expressed in HEK-Blue hTLR9 cells assessed as inhibition of TLR9 by cell based assay	ic50	0.0320	uM
4-[(2R,6S)-2-methyl-6-[[6-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)spiro[1H-2-benzofuran-3,3’-azetidine]-1’-yl]methyl]morpholin-4-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile	1817772: Inhibition of human TLR9 expressed in HEK-Blue hTLR9 cells assessed as inhibition of TLR9 by cell based assay	ic50	0.0320	uM
4-[3-[5-methoxy-2-(7-piperazin-1-ylimidazo[1,2-a]pyridin-2-yl)phenoxy]propyl]morpholine	1874521: Antagonist activity at human TLR9 expressed in HEK-blue hTLR9 cells assessed as inhibition of CpGB-induced NFkappaB activation preincubated with compound for 1 hrs followed by CpGB addition and measured next day by SEAP-based spectrophotometry assay	ic50	0.0350	uM
5,6-dimethyl-2-[4-(4-methylpiperazin-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)pyrimidin-4-amine	1171366: Antagonist activity at human TLR9 transfected in HEK293 cells after 6 hrs by NF-kappaB luciferase reporter assay	ic50	0.0350	uM
1-methyl-N-[3-[6-(3-pyrrolidin-1-ylpropoxy)-1,3-benzoxazol-2-yl]phenyl]piperidin-4-amine	1452739: Antagonist activity at human TLR9 expressed in HEK293 cells assessed as inhibition of CpGB-induced NF-kappaB activation after 24 hrs by spectrophotometry based SEAP reporter gene assay	ic50	0.0370	uM
2-(2,4-dimethoxyphenyl)-N-(3-imidazol-1-ylpropyl)imidazo[1,2-a]pyridin-7-amine	1874521: Antagonist activity at human TLR9 expressed in HEK-blue hTLR9 cells assessed as inhibition of CpGB-induced NFkappaB activation preincubated with compound for 1 hrs followed by CpGB addition and measured next day by SEAP-based spectrophotometry assay	ic50	0.0380	uM
5-[(2S,6R)-2-[[3-[(4aR,7aR)-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazin-6-yl]spiro[5H-furo[3,4-b]pyridine-7,3’-azetidine]-1’-yl]methyl]-6-methylmorpholin-4-yl]-2-deuterioquinoline-8-carbonitrile	1817772: Inhibition of human TLR9 expressed in HEK-Blue hTLR9 cells assessed as inhibition of TLR9 by cell based assay	ic50	0.0390	uM
7-(4-cyclopentylpiperazin-1-yl)-2-(2,4-dimethoxyphenyl)-3-(pyrrolidin-1-ylmethyl)imidazo[1,2-a]pyridine	1874521: Antagonist activity at human TLR9 expressed in HEK-blue hTLR9 cells assessed as inhibition of CpGB-induced NFkappaB activation preincubated with compound for 1 hrs followed by CpGB addition and measured next day by SEAP-based spectrophotometry assay	ic50	0.0390	uM
4-(4-cyclopentylpiperazin-1-yl)-N-[(4-fluorophenyl)methyl]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-amine	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0400	uM
6-methoxy-N,N-dimethyl-4-(4-methylpiperazin-1-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-2-amine	1422466: Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis	ic50	0.0400	uM
6-(4-ethylpiperazin-1-yl)-N-[(4-fluorophenyl)methyl]-9-(3-pyrrolidin-1-ylpropyl)purin-2-amine	1814740: Antagonist activity at human TLR9 expressed in HEK-blue-HTLR7 cells assessed as inhibition of CpGB-induced NFkappaB activation measured after overnight incubation by SEAP-based spectrophotometry assay	ic50	0.0400	uM
2-(2,6-dimethyl-4-pyridinyl)-4-methyl-6-piperidin-4-yl-9H-carbazole	1768802: Inhibition of human TLR9 in HEK-Blue hTLR9 cells assessed as reduction in ODN2006-activated NF-KappaB by SEAP reporter assay	ic50	0.0400	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CPG-oligonucleotide	increases activity, affects localization, affects cotreatment, increases expression, increases reaction (+2 more)	4
Paraquat	increases secretion, affects cotreatment, affects reaction, increases expression, decreases reaction (+1 more)	3
CpG ODN 2216	increases activity	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
Chloroquine	increases activity, increases expression, decreases expression, increases reaction, decreases reaction	2
Cadmium Chloride	decreases expression, increases expression	2
2-anisidine	affects expression	1
hydroxyhydroquinone	decreases expression, decreases reaction	1
4-aminobenzhydrazide	decreases expression, decreases reaction	1
epigallocatechin gallate	increases expression, decreases reaction	1
CGP 52608	increases reaction, affects binding	1
lipopolysaccharide, E. coli O26-B6	increases expression	1
CpG ODN 2006	decreases reaction, increases activity, affects binding	1
CpG ODN 2395	affects binding, decreases reaction, increases activity	1
theaflavin-3,3’-digallate	affects expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Cisplatin	decreases response to substance, decreases expression	1
Hydroxychloroquine	decreases expression	1
Lipopolysaccharides	increases expression	1
Melatonin	decreases reaction, increases expression	1
Oxygen	decreases reaction, increases expression, increases reaction	1
Ozone	increases expression	1
Rotenone	increases expression	1
Silver Compounds	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

132 unique, capped per target: 125 binding, 7 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1247821	Binding	Inhibition of TLR7/TLR9-mediated activation of aldrithiol-2-treated HIV1 Ada-stimulated human PBMC assessed as CD86 expressing cells at 100 uM after 20 hrs by flow cytometry	Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation. — *Antimicrob Agents Chemother*
CHEMBL2169112	Functional	Agonist activity at human TLR9 expressed in Ramos blue cells assessed as stimulation of NF-kB/AP-1 activity at 20 uM incubated for 18 hrs using quanti blue assay based SEAP reporter gene assay	Immunomodulatory properties of novel nucleotide oligomerization domain 2 (nod2) agonistic desmuramyldipeptides. — *J Med Chem*

Cellosaurus cell lines

11 cell lines: 8 transformed cell line, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8CU	HEK-Blue-Lucia hTLR9 (NF/IL8)	Transformed cell line	Female
CVCL_D7A5	Leeporter HEK293 TLR9/NF-kB luciferase	Transformed cell line	Female
CVCL_E6V4	Genomeditech HEK-293 H_TLR9 Reporter	Transformed cell line	Female
CVCL_E8FD	THP1-Dual hTLR9	Cancer cell line	Male
CVCL_IM86	HEK-Blue hTLR9	Transformed cell line	Female
CVCL_RQ78	HEK 293/TLR9/NF-kB Luciferase Reporter	Transformed cell line	Female
CVCL_VI46	HEK-TLR9-YFP	Transformed cell line	Female
CVCL_XI46	CAL-1 TLR9 mCherry	Cancer cell line	Male
CVCL_XI47	THP-1 TLR9 mCherry	Cancer cell line	Male
CVCL_Y412	293XL/hTLR9-HA	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

37 trials:

NCT	Phase	Status	Title
NCT01574313	Phase 4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	Phase 4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	Phase 4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT03664674	Phase 3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	Phase 3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	Phase 3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT05420350	Phase 2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	Phase 2	UNKNOWN	Laser Acupuncture for Meniere Disease
NCT04674735	Phase 1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT03792360	Phase 1	WITHDRAWN	Adipose Derived SVF for Aero-digestive & Enterocutaneous Fistulae
NCT04218123	Phase 2/3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	Phase 1/2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	Early Phase 1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	UNKNOWN	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?
NCT04935970	Not specified	UNKNOWN	Metabolic Disorders and Vertigo
NCT05322538	Not specified	NOT_YET_RECRUITING	Menier’s Disease - Bone Density Study
NCT05328895	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT05424302	Not specified	RECRUITING	Effect of Peripheral Vestibular Disease Location on Outcomes Following Home-based Virtual Reality Vestibular Therapy
NCT05582148	Not specified	UNKNOWN	Meniere Disease and Hearing Aids
NCT05844657	Not specified	COMPLETED	Comprehensive Evaluation in Patients With Meniere’s Disease
NCT05960786	Not specified	COMPLETED	Treating the Symptoms of Vertigo in a Real-world Setting Using the OtoBand
NCT06278129	Not specified	UNKNOWN	Evaluation of the Diagnostic and Prognostic Efficacy of MRI in Acute Sensorineural Hearing Loss and Ménière’s Disease
NCT06544590	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT07272473	Not specified	RECRUITING	Effects of Cervical Mobilization on Dizziness, Balance, and Joint Position Sense in Patients With Meniere’s Disease
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02364843	Not specified	TERMINATED	A Physiological Study to Determine the Enteral Threonine Requirements in Infants Aged 1 to 6 Months
NCT03455881	Not specified	UNKNOWN	Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
NCT03730454	Not specified	ACTIVE_NOT_RECRUITING	Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair
NCT07687628	Not specified	RECRUITING	Camera-based Endoscopy Allows Spontaneous Breathing Diagnostic Management in Neonates With Tracheoesophageal Fistula

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TLR9 across ~30M SureChEMBL compounds — explore on Sugi Predict.