TLR9

toll like receptor 9, the group of CD molecules|Toll like receptors|My-T-BRC complex

Basic information

Region (hg38): 3:52221079-52225645

Links

ENSG00000239732 ∙ NCBI:54106 ∙ OMIM:605474 ∙ HGNC:15633 ∙ Uniprot:Q9NR96 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLR9 gene.

• Inborn genetic diseases (40 variants)
• not provided (17 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLR9 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	7	12
missense			38	5	2	45
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	38	10	9

Variants in TLR9

This is a list of pathogenic ClinVar variants found in the TLR9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-52221223-G-A			Benign (Jul 27, 2018)
3-52221264-G-T		not specified	Uncertain significance (Nov 10, 2022)
3-52221273-T-C		not specified	Uncertain significance (Apr 22, 2022)
3-52221285-T-C		not specified	Uncertain significance (Dec 28, 2022)
3-52221372-G-A		not specified	Uncertain significance (Apr 26, 2023)
3-52221380-C-T		not specified	Uncertain significance (Jan 11, 2023)
3-52221387-G-A		not specified	Uncertain significance (Dec 16, 2022)
3-52221399-G-A		not specified	Uncertain significance (Aug 13, 2021)
3-52221447-G-A		not specified	Uncertain significance (Jun 28, 2022)
3-52221474-G-A		not specified	Uncertain significance (Oct 28, 2023)
3-52221602-C-T		not specified	Uncertain significance (Jan 27, 2022)
3-52221648-C-T			Uncertain significance (Feb 28, 2023)
3-52221687-C-T		not specified	Uncertain significance (Mar 01, 2023)
3-52221710-G-C		not specified	Uncertain significance (Jan 10, 2022)
3-52221728-C-T			Benign (Jul 20, 2018)
3-52221740-C-T		not specified	Uncertain significance (Jun 12, 2023)
3-52221814-C-A		not specified	Uncertain significance (Aug 15, 2023)
3-52221897-G-A		not specified	Uncertain significance (Mar 29, 2022)
3-52221904-C-T			Benign (May 03, 2018)
3-52221936-C-T		not specified	Uncertain significance (Feb 07, 2023)
3-52221938-G-A		not specified	Uncertain significance (Aug 02, 2023)
3-52221956-C-G		not specified	Uncertain significance (Sep 29, 2023)
3-52221957-G-A		not specified	Uncertain significance (Sep 27, 2021)
3-52222068-T-C		not specified	Likely benign (Aug 02, 2021)
3-52222165-G-T			Likely benign (Jul 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLR9	protein_coding	protein_coding	ENST00000360658	2	18088

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000981	0.997	125678	0	70	125748	0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	485	648	0.749	0.0000432	6692
Missense in Polyphen		145	240.51	0.60289		2804
Synonymous	-0.212	296	291	1.02	0.0000187	2238
Loss of Function	2.63	13	28.0	0.464	0.00000155	252

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000337	0.000336
Ashkenazi Jewish	0.00	0.00
East Asian	0.00125	0.00125
Finnish	0.00	0.00
European (Non-Finnish)	0.000283	0.000273
Middle Eastern	0.00125	0.00125
South Asian	0.000237	0.000229
Other	0.000339	0.000326

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:11564765, PubMed:17932028). Controls lymphocyte response to Helicobacter infection (By similarity). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (PubMed:23857366). {ECO:0000250|UniProtKB:Q9EQU3, ECO:0000269|PubMed:11564765, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:23857366}.
• Pathway: African trypanosomiasis - Homo sapiens (human);Malaria - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Measles - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Toll-like Receptor Signaling;Simplified Depiction of MYD88 Distinct Input-Output Pathway;Toll-like Receptor Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;Signal Transduction;TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling;toll-like receptor pathway;Toll Like Receptor 9 (TLR9) Cascade;Trafficking and processing of endosomal TLR;Toll-Like Receptors Cascades;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Innate Immune System;Immune System;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) (Consensus)

Recessive Scores

• pRec: 0.502

Intolerance Scores

• loftool: 0.545
• rvis_EVS: -1.61
• rvis_percentile_EVS: 3

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.432
• ghis: 0.397

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.721

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tlr9
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; immune system phenotype; renal/urinary system phenotype; digestive/alimentary phenotype

Gene ontology

• Biological process: toll-like receptor signaling pathway;response to molecule of bacterial origin;positive regulation of immunoglobulin production;MyD88-dependent toll-like receptor signaling pathway;inflammatory response;immune response;I-kappaB kinase/NF-kappaB signaling;I-kappaB phosphorylation;positive regulation of gene expression;maintenance of gastrointestinal epithelium;positive regulation of B cell proliferation;negative regulation of NF-kappaB transcription factor activity;tumor necrosis factor production;negative regulation of interleukin-6 production;negative regulation of interleukin-8 production;positive regulation of chemokine production;positive regulation of granulocyte macrophage colony-stimulating factor production;positive regulation of interferon-beta production;positive regulation of interleukin-10 production;positive regulation of interleukin-12 production;positive regulation of interleukin-18 production;positive regulation of interleukin-6 production;positive regulation of interleukin-8 production;positive regulation of tumor necrosis factor production;negative regulation of toll-like receptor signaling pathway;positive regulation of toll-like receptor signaling pathway;toll-like receptor 9 signaling pathway;regulation of toll-like receptor 9 signaling pathway;phosphatidylinositol-3-phosphate biosynthetic process;defense response to bacterium;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of MAPK cascade;positive regulation of JUN kinase activity;positive regulation of interferon-gamma biosynthetic process;innate immune response;positive regulation of interferon-alpha biosynthetic process;positive regulation of interferon-beta biosynthetic process;positive regulation of interleukin-8 biosynthetic process;regulation of B cell differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of JNK cascade;regulation of cytokine secretion;positive regulation of inflammatory response;defense response to Gram-negative bacterium;positive regulation of B cell activation;positive regulation of NF-kappaB transcription factor activity;defense response to virus;positive regulation of nitric-oxide synthase biosynthetic process;positive regulation of NIK/NF-kappaB signaling;negative regulation of calcium-transporting ATPase activity
• Cellular component: Golgi membrane;extracellular region;cytoplasm;lysosome;endosome;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;endosome membrane;integral component of membrane;basolateral plasma membrane;apical plasma membrane;early phagosome;endolysosome membrane
• Molecular function: transmembrane signaling receptor activity;interleukin-1 receptor binding;signaling pattern recognition receptor activity;1-phosphatidylinositol-3-kinase activity;siRNA binding;protein homodimerization activity;unmethylated CpG binding