TLR6

toll like receptor 6, the group of CD molecules|Toll like receptors

Basic information

Region (hg38): 4:38822896-38856817

Links

ENSG00000174130 ∙ NCBI:10333 ∙ OMIM:605403 ∙ HGNC:16711 ∙ Uniprot:Q9Y2C9 ∙ 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 TLR6 gene.

• Inborn genetic diseases (27 variants)
• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLR6 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					1	1
missense			25	2	2	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	25	2	3

Variants in TLR6

This is a list of pathogenic ClinVar variants found in the TLR6 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-38827147-T-C		not specified	Uncertain significance (May 25, 2022)
4-38827166-G-A		not specified	Uncertain significance (Sep 29, 2023)
4-38827234-T-C		not specified	Uncertain significance (Mar 01, 2023)
4-38827252-T-C		not specified	Uncertain significance (Nov 09, 2021)
4-38827348-C-G		not specified	Uncertain significance (Nov 15, 2021)
4-38827350-C-G			not provided (-)
4-38827433-C-G		not specified	Uncertain significance (Nov 18, 2022)
4-38827444-T-C		not specified	Uncertain significance (Oct 05, 2023)
4-38827472-C-A		not specified	Uncertain significance (Dec 11, 2023)
4-38827522-T-C		not specified	Uncertain significance (Aug 08, 2022)
4-38827543-G-T		not specified	Uncertain significance (May 27, 2022)
4-38827564-T-C		not specified	Uncertain significance (Mar 24, 2023)
4-38827583-T-A		not specified	Uncertain significance (Apr 12, 2023)
4-38827597-C-T		not specified	Likely benign (Jan 18, 2022)
4-38827615-T-G		not specified	Uncertain significance (May 15, 2023)
4-38827699-C-A			Benign (Jul 04, 2018)
4-38827708-A-G		not specified	Uncertain significance (Mar 07, 2023)
4-38827743-CAT-C		Abnormality of neuronal migration	Benign (Oct 31, 2014)
4-38827798-T-C		not specified	Uncertain significance (Oct 04, 2022)
4-38827844-T-C		not specified	Uncertain significance (Dec 20, 2021)
4-38827850-T-G		not specified	Likely benign (Feb 28, 2024)
4-38828081-C-T			Benign (Jul 31, 2018)
4-38828149-T-G			not provided (-)
4-38828384-C-T		not specified	Uncertain significance (Dec 06, 2022)
4-38828461-A-C		not specified	Uncertain significance (Nov 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLR6	protein_coding	protein_coding	ENST00000436693	1	33103

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000225	0.980	125648	1	99	125748	0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.936	347	400	0.868	0.0000198	5313
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00173	0.00173
Ashkenazi Jewish	0.00	0.00
East Asian	0.000652	0.000653
Finnish	0.00	0.00
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.000652	0.000653
South Asian	0.000524	0.000490
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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;Toll-like Receptor Signaling;Simplified Depiction of MYD88 Distinct Input-Output Pathway;Toll-like Receptor Signaling Pathway;toll-like receptor pathway;Toll-Like Receptors Cascades;Innate Immune System;Immune System;Adaptive Immune System;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;Regulation of TLR by endogenous ligand;ER-Phagosome pathway;Toll Like Receptor 4 (TLR4) Cascade;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Endogenous TLR signaling (Consensus)

Recessive Scores

• pRec: 0.243

Intolerance Scores

• loftool: 0.596
• rvis_EVS: 0.89
• rvis_percentile_EVS: 89.29

Haploinsufficiency Scores

• pHI: 0.102
• hipred: N
• hipred_score: 0.132
• ghis: 0.460

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.180

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tlr6
• Phenotype: hematopoietic system phenotype; reproductive system phenotype; immune system phenotype

Gene ontology

• Biological process: microglial cell activation;cell activation;toll-like receptor signaling pathway;MyD88-dependent toll-like receptor signaling pathway;inflammatory response;immune response;signal transduction;activation of NF-kappaB-inducing kinase activity;positive regulation of gene expression;negative regulation of toll-like receptor 2 signaling pathway;toll-like receptor 6 signaling pathway;TRIF-dependent toll-like receptor signaling pathway;toll-like receptor TLR6:TLR2 signaling pathway;detection of diacyl bacterial lipopeptide;defense response to bacterium;positive regulation of macrophage activation;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of JUN kinase activity;innate immune response;positive regulation of interleukin-6 biosynthetic process;positive regulation of nitric oxide biosynthetic process;nitric oxide metabolic process;interleukin-1 beta secretion;positive regulation of NF-kappaB transcription factor activity;cellular response to diacyl bacterial lipopeptide;cellular response to oxidised low-density lipoprotein particle stimulus;positive regulation of cytokine production involved in inflammatory response;positive regulation of NLRP3 inflammasome complex assembly;positive regulation of oxidative stress-induced neuron death;positive regulation of reactive oxygen species biosynthetic process;cellular response to amyloid-beta;negative regulation of interleukin-8 secretion
• Cellular component: Golgi apparatus;plasma membrane;integral component of plasma membrane;phagocytic vesicle membrane;Toll-like receptor 2-Toll-like receptor 6 protein complex;receptor complex;membrane raft
• Molecular function: amyloid-beta binding;transmembrane signaling receptor activity;signaling receptor binding;protein binding;Toll-like receptor 2 binding;signaling receptor activity;identical protein binding;protein heterodimerization activity;lipopeptide binding