TLR9

protein-coding

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

Gene 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]

MANE transcript

NM_017442.4

Inheritance

—

ClinVar variants

P:1U:115B:25

Top phenotype

Meniere disease

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr3:52,221,080-52,225,645

External References & Databases

Ensembl (ENSG00000239732)

Transcript & Mutation Effects

hg38 • Region Span ~4.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TLR9 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 19

Meniere diseaseTotal: 2

Esophageal atresia/tracheoesophageal fistulaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017442.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar	7 clinvar	13
missense		1 clinvar	115 clinvar	10 clinvar	2 clinvar	128
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	115	16	9	141

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017442.4	RefSeq	NP_059138.1	2	MANE Select
ENST00000360658.3	Ensembl	ENSP00000353874.2	2	MANE Select
ENST00001144037.1	Ensembl	ENSP00000808858.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

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

Molecular Function

transmembrane signaling receptor activity
interleukin-1 receptor binding
signaling pattern recognition receptor activity
1-phosphatidylinositol-3-kinase activity
siRNA binding

Cellular Component

Golgi membrane
extracellular region
cytoplasm
lysosome
endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360658
Coding exons: 2
Length: 18088
Individuals with no LoFs: 125678
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125748
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.27	485	648	0.749	0.0000432	6692
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0013	0.0013	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00027	rare
South Asian	0.00024	0.00023	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.502

Intolerance Scores

LoFtool: 0.545
RVIS EVS: -1.61
RVIS percentile EVS: 3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.721

Gene Damage Prediction

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