TLR9 toll like receptor 9 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TLR9provided by HGNC
Official Full Name: toll like receptor 9provided by HGNC
Primary source: HGNC:HGNC:15633
See related: Ensembl:ENSG00000239732 MIM:605474
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CD289
Summary: 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. [provided by RefSeq, Aug 2017]
Expression: Broad expression in lymph node (RPKM 2.9), spleen (RPKM 1.9) and 16 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 3p21.2

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	3	NC_000003.12 (52221080..52226163, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (52255096..52260179, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Study report that bacterial CpG DNA and mtDNA, a pathogen-associated molecular pattern, impair phagocytosis through Toll-like receptor 9 (TLR9)-mediated release of NE and proteinase 3 (PR3) and subsequent down-regulation of C5aR, thereby reducing phagocytosis-induced apoptosis in human polymorphonuclear neutrophil granulocytes.
Title: 15-Epi-LXA4 and 17-epi-RvD1 restore TLR9-mediated impaired neutrophil phagocytosis and accelerate resolution of lung inflammation.
Increased signaling potentials in peripheral B cells of pSS patients in response to TLR7 and -9 stimulation.
Title: Single Cell Based Phosphorylation Profiling Identifies Alterations in Toll-Like Receptor 7 and 9 Signaling in Patients With Primary Sjögren's Syndrome.
These findings indicate that TLR7 SNP (rs2074109) could be one of the factors for predisposition to HIV-1 and TLR9 1635A/G genotype and allele might have a role in HIV-1 disease progression in Indian population.
Title: Polymorphisms in Toll-Like Receptors (TLRs)-7 and 9 Genes in Indian Population with Progressive and Nonprogressive HIV-1 Infection.
An abnormal increase in TLR9 expression was observed in systemic lupus erythematosus patients compared to controls.
Title: Expression Level of TLR9, but not Hypomethylation, Is Correlated With SLE Disease Activity.
TLR9 plays critical roles in regulating peritoneal immunity via suppression of chemokine production by fibroblastic reticular cells
Title: TLR9 signaling in fibroblastic reticular cells regulates peritoneal immunity.
Investigated the effect of serum cell-free DNA (cfDNA) and placental cell free-fetal DNA (cffDNA) on inflammatory responses using normal pregnant women and preeclampsia patients; found the expression levels of toll like receptor 9 (TLR9) and amount of cffDNA from the placenta were higher in the preeclampsia patients.
Title: Preeclamptic patient-derived circulating cell-free DNA activates the production of inflammatory cytokines via toll-like receptor 9 signalling in the human placenta.
TLR9-1486TT genotype was associated with a decreased risk of hepatocellular carcinoma recurrence.
Title: TLR9-1486C/T polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation.
Our results indicated for the first time that the functional -1237 T/C polymorphism and mRNA expression of TLR9 gene may be considered as protective factors for NPC severity and progression.
Title: Functional Polymorphisms and Gene Expression of TLR9 Gene as Protective Factors for Nasopharyngeal Carcinoma Severity and Progression.
TLR9 mediates autophagy and apoptosis in salivary gland cells via p38/JNK pathway.
Title: Toll-like receptor 9 signaling promotes autophagy and apoptosis via divergent functions of the p38/JNK pathway in human salivary gland cells.
We show that, when macrophages are stimulated with the TLR9 agonist CpG oligodeoxynucleotides (ODN), the secreted EVs transport ODN into naive macrophages and induce the release of chemokine TNF-alpha. In addition, these EVs transfer Cdc42 into recipient cells, resulting in further enhancement of their cellular uptake
Title: Extracellular vesicles derived from ODN-stimulated macrophages transfer and activate Cdc42 in recipient cells and thereby increase cellular permissiveness to EV uptake.

Submit: New GeneRIF Correction See all GeneRIFs (615)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Genome-wide association analysis identifies 13 new risk loci for schizophrenia. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 inhibits TLR9-mediated upregulation of CD83 and the secretion of inflammatory cytokines TNF-alpha and IL-6, and chemokine IP10 in plasmacytoid dendritic cells (pDC)	PubMed
	env	TLR-9-induced IFN-alpha production is inhibited by both monomeric and trimeric HIV-1 gp120 in plasmacytoid dendritic cells (pDC)	PubMed
	env	Treatment of HIV-1 gp120 to astroglia displays significant decreases in TLR9	PubMed
Envelope surface glycoprotein gp160, precursor	env	Combined activation of TLR7/8 and TLR9 by TLR7/8 and TLR9 agonists induces the highest titers of binding, neutralizing, and antibody-dependent cellular cytotoxicity-mediating antibodies against HIV-1 Env/gp140	PubMed
Tat	tat	Treatment of HIV-1 Tat to astroglia displays significant decreases in TLR9 expression	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

TLR9_1094 (e-PCR)
- UniSTS:277823

PMC55404P4 (e-PCR)
- UniSTS:273343

PMC128073P9 (e-PCR)
- UniSTS:270571

Homology

Homologs of the TLR9 gene: The TLR9 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, and frog.
Orthologs from Annotation Pipeline: 81 organisms have orthologs with human gene TLR9
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
interleukin-1 receptor binding	IPI Inferred from Physical Interaction more info	PubMed
pattern recognition receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
siRNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
transmembrane signaling receptor activity	IEA Inferred from Electronic Annotation more info
unmethylated CpG binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
I-kappaB kinase/NF-kappaB signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
I-kappaB phosphorylation	IDA Inferred from Direct Assay more info	PubMed
MyD88-dependent toll-like receptor signaling pathway	IEA Inferred from Electronic Annotation more info
defense response to Gram-negative bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
defense response to bacterium	NAS Non-traceable Author Statement more info	PubMed
defense response to virus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
immune response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
inflammatory response	IEA Inferred from Electronic Annotation more info
innate immune response	TAS Traceable Author Statement more info	PubMed
maintenance of gastrointestinal epithelium	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of calcium-transporting ATPase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of toll-like receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of B cell activation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of B cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	IDA Inferred from Direct Assay more info	PubMed
positive regulation of JNK cascade	IC Inferred by Curator more info	PubMed
positive regulation of JUN kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
positive regulation of NF-kappaB transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of NIK/NF-kappaB signaling	IDA Inferred from Direct Assay more info	PubMed
positive regulation of chemokine production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
positive regulation of granulocyte macrophage colony-stimulating factor production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of immunoglobulin production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
positive regulation of interferon-alpha production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interferon-beta production	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of interferon-beta production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interferon-beta production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interferon-gamma production	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of interferon-gamma production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interleukin-10 production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-12 production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-18 production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-6 production	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of interleukin-6 production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interleukin-8 production	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of nitric-oxide synthase biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of toll-like receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
regulation of B cell differentiation	IDA Inferred from Direct Assay more info	PubMed
regulation of cytokine secretion	IEA Inferred from Electronic Annotation more info
regulation of toll-like receptor 9 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
response to molecule of bacterial origin	TAS Traceable Author Statement more info	PubMed
toll-like receptor 9 signaling pathway	TAS Traceable Author Statement more info
toll-like receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
toll-like receptor signaling pathway	TAS Traceable Author Statement more info
tumor necrosis factor production	IBA Inferred from Biological aspect of Ancestor more info	PubMed
tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
Golgi membrane	TAS Traceable Author Statement more info
apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
early phagosome	ISS Inferred from Sequence or Structural Similarity more info
endolysosome	ISS Inferred from Sequence or Structural Similarity more info
endolysosome membrane	TAS Traceable Author Statement more info
endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
endosome	ISS Inferred from Sequence or Structural Similarity more info
endosome membrane	TAS Traceable Author Statement more info
extracellular region	NAS Non-traceable Author Statement more info	PubMed
integral component of membrane	IEA Inferred from Electronic Annotation more info
lysosome	ISS Inferred from Sequence or Structural Similarity more info
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: toll-like receptor 9

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033933.1 RefSeqGene

Range

5001..10084

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_017442.4 → NP_059138.1 toll-like receptor 9 precursor

See identical proteins and their annotated locations for NP_059138.1

Status: REVIEWED

Source sequence(s)

AF245704, AF259262, BC032713

Consensus CDS

CCDS2848.1

UniProtKB/Swiss-Prot

Q9NR96

Related

ENSP00000353874.2, ENST00000360658.2

Conserved Domains (4) summary

cd00116
Location:476 → 739

LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...

sd00033
Location:476 → 497

LRR_RI; leucine-rich repeat [structural motif]

pfam13855
Location:496 → 555

LRR_8; Leucine rich repeat

cl23749
Location:870 → 1009

TIR_2; TIR domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20200522

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p13 Primary Assembly

Range

52221080..52226163 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_138688.1: Suppressed sequence

Description

NM_138688.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.