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; AllianceGenome:HGNC:15633
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
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Genomic context

Location:: 3p21.2

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (52221080..52225645, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (52253966..52258531, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (52255096..52259661, 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Adenosine deaminase 2 regulates the activation of the toll-like receptor 9 in response to nucleic acids.
Title: Adenosine deaminase 2 regulates the activation of the toll-like receptor 9 in response to nucleic acids.
Impact of TLR9 and TLR7 gene polymorphisms on prognosis and survival of patients with oral squamous cell carcinoma.
Title: Impact of TLR9 and TLR7 gene polymorphisms on prognosis and survival of patients with oral squamous cell carcinoma.
Revealing of TLR-9 gene polymorphisms by qPCR HRM technique and their influence on TLR-9 serum level in acute myeloid leukemia patients: Case-control study.
Title: Revealing of TLR-9 gene polymorphisms by qPCR HRM technique and their influence on TLR-9 serum level in acute myeloid leukemia patients: Case-control study.
Loss of Toll-like receptor 9 protects from hepatocellular carcinoma in murine models of chronic liver disease.
Title: Loss of Toll-like receptor 9 protects from hepatocellular carcinoma in murine models of chronic liver disease.
Investigation of TLR2 (-196 to -174del) and TLR9 (T-1486C) Gene Polymorphisms Association with Inflammatory Bowel Diseases.
Title: Investigation of TLR2 (-196 to -174del) and TLR9 (T-1486C) Gene Polymorphisms Association with Inflammatory Bowel Diseases.
Synonymous mutations in TLR2 and TLR9 genes decrease COPD susceptibility in the Chinese Han population.
Title: Synonymous mutations in TLR2 and TLR9 genes decrease COPD susceptibility in the Chinese Han population.
Epstein-Barr virus suppresses N[6]-methyladenosine modification of TLR9 to promote immune evasion.
Title: Epstein-Barr virus suppresses N(6)-methyladenosine modification of TLR9 to promote immune evasion.
Tubular expression of Toll-like receptor 9 in lupus and primary membranous nephropathy.
Title: Tubular expression of Toll-like receptor 9 in lupus and primary membranous nephropathy.
Relationship of Toll-Like Receptor 7, 9, and 10 Polymorphisms and the Severity of Coronavirus Disease 2019.
Title: Relationship of Toll-Like Receptor 7, 9, and 10 Polymorphisms and the Severity of Coronavirus Disease 2019.
Mutated Toll-like receptor 9 increases Alzheimer's disease risk by compromising innate immunity protection.
Title: Mutated Toll-like receptor 9 increases Alzheimer's disease risk by compromising innate immunity protection.

Submit: New GeneRIF Correction See all GeneRIFs (724)

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

EBI GWAS Catalog

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

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in MyD88-dependent toll-like receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to chloroquine	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to metal ion	IEA Inferred from Electronic Annotation more info
involved_in defense response to Gram-negative bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to bacterium	NAS Non-traceable Author Statement more info	PubMed
involved_in defense response to virus	IBA Inferred from Biological aspect of Ancestor more info
involved_in detection of molecule of bacterial origin	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	TAS Traceable Author Statement more info	PubMed
involved_in maintenance of gastrointestinal epithelium	ISS Inferred from Sequence or Structural Similarity more info
involved_in male gonad development	IEA Inferred from Electronic Annotation more info
involved_in microglial cell activation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of ATPase-coupled calcium transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of B cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of B cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of JNK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of autophagy	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chemokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of granulocyte macrophage colony-stimulating factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of immunoglobulin production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
involved_in positive regulation of interferon-alpha production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interferon-beta production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interferon-beta production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-10 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-12 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-18 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-6 production	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of interleukin-6 production	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of intestinal epithelial cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of toll-like receptor 9 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of type II interferon production	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of B cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of dendritic cell cytokine production	IEA Inferred from Electronic Annotation more info
involved_in toll-like receptor 9 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in toll-like receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in toll-like receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed

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

5519..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

B3Y661, D1CS56, Q6UVZ2, Q9HD68, Q9HD69, Q9HD70, Q9NR96, Q9NYC2, Q9NYC3

UniProtKB/TrEMBL

B6CH46, C3W5P5, D1CS61, D1CS62

Related

ENSP00000353874.2, ENST00000360658.3

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: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

52221080..52225645 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

52253966..52258531 complement

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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.