TLR6
protein-codingtoll like receptor 6, the group of CD molecules|Toll like receptors
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. The various TLRs exhibit different patterns of expression. This receptor functionally interacts with toll-like receptor 2 to mediate cellular response to bacterial lipoproteins. A Ser249Pro polymorphism in the extracellular domain of the encoded protein may be associated with an increased of asthma is some populations.[provided by RefSeq, Jan 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.9 kbGenCC 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 TLR6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006068.5. 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 | 1 | 1 | ||||
| missense | 89 | 4 | 2 | 95 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 91 | 4 | 4 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006059.2 | 1 | MANE Select | |
| Ensembl | ENSP00000424718.2 | 1 | MANE Select | |
| RefSeq | NP_001381482.1 | 1 | Standard | |
| Ensembl | ENSP00000371376.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Phagosome - Homo sapiens (human)
- Chagas disease (American trypanosomiasis) - Homo sapiens (human)
- Toll-like receptor signaling pathway - Homo sapiens (human)
- Tuberculosis - Homo sapiens (human)
- Regulation of toll-like receptor signaling pathway
Biological Process
- microglial cell activation
- cell activation
- toll-like receptor signaling pathway
- MyD88-dependent toll-like receptor signaling pathway
- inflammatory response
Molecular Function
- amyloid-beta binding
- transmembrane signaling receptor activity
- signaling receptor binding
- protein binding
- Toll-like receptor 2 binding
Cellular Component
- Golgi apparatus
- plasma membrane
- integral component of plasma membrane
- phagocytic vesicle membrane
- Toll-like receptor 2-Toll-like receptor 6 protein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000436693
- Coding exons
- 1
- Length
- 33103
- Individuals with no LoFs
- 125648
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 99
- Defined
- 125748
- p
- 0.000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.936 | 347 | 400 | 0.868 | 0.0000198 | 5313 |
| Missense (PolyPhen) | 65 | 80.616 | 0.80629 | 1203 | ||
| Synonymous | 0.516 | 149 | 157 | 0.948 | 0.00000852 | 1470 |
| Loss of Function | 2.10 | 11 | 21.5 | 0.512 | 9.19e-7 | 335 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00086 | 0.00086 | rare |
| Latino/Admixed American | 0.00087 | 0.00087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00052 | 0.00049 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Participates in the innate immune response to Gram- positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides (PubMed:20037584). In response to diacylated lipopeptides, forms the activation cluster TLR2:TLR6:CD14:CD36, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (PubMed:16880211). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR2 (PubMed:11441107). In complex with TLR4, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid- beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B- dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion (PubMed:11441107, PubMed:20037584). {ECO:0000269|PubMed:11441107, ECO:0000269|PubMed:16880211, ECO:0000269|PubMed:20037584}.;
Recessive Scores
- pRec
- 0.243
Intolerance Scores
- LoFtool
- 0.596
- RVIS EVS
- 0.89
- RVIS percentile EVS
- 89.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.180
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |