TLR2
toll like receptor 2, the group of CD molecules|Toll like receptors
Basic information
Region (hg38): 4:153684050-153706260
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLR2 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 | 7 | |||||
| missense | 49 | 55 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 50 | 10 | 3 |
Variants in TLR2
This is a list of pathogenic ClinVar variants found in the TLR2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-153702929-G-T | not specified | Uncertain significance (May 18, 2022) | ||
| 4-153702960-C-A | not specified | Uncertain significance (Apr 13, 2023) | ||
| 4-153702978-A-G | not specified | Uncertain significance (May 16, 2023) | ||
| 4-153702984-C-T | TLR2-related disorder | Likely benign (Jun 02, 2019) | ||
| 4-153703020-G-A | not specified | Uncertain significance (Oct 07, 2024) | ||
| 4-153703021-C-A | Benign (Jun 26, 2018) | |||
| 4-153703026-C-T | Uncertain significance (-) | |||
| 4-153703094-A-G | not specified | Uncertain significance (Nov 12, 2024) | ||
| 4-153703102-C-T | TLR2-related disorder | Likely benign (Feb 21, 2019) | ||
| 4-153703136-A-T | not specified | Uncertain significance (Dec 03, 2024) | ||
| 4-153703149-T-C | TLR2-related disorder | Likely benign (Nov 12, 2019) | ||
| 4-153703172-A-G | not provided (-) | |||
| 4-153703178-A-G | Leprosy, susceptibility to, 3;Colorectal cancer;Mycobacterium tuberculosis, susceptibility to • TLR2-related disorder | Conflicting classifications of pathogenicity (Oct 05, 2022) | ||
| 4-153703207-CA-C | Colorectal cancer | Uncertain significance (Sep 28, 2022) | ||
| 4-153703287-C-T | not specified | Uncertain significance (Jun 16, 2024) | ||
| 4-153703295-A-G | not specified | Uncertain significance (Oct 13, 2023) | ||
| 4-153703296-A-G | not specified | Uncertain significance (Oct 01, 2024) | ||
| 4-153703337-C-T | not specified | Uncertain significance (Dec 20, 2023) | ||
| 4-153703344-C-G | not specified | Uncertain significance (Nov 15, 2021) | ||
| 4-153703356-A-T | not specified | Uncertain significance (Nov 24, 2024) | ||
| 4-153703380-A-C | not specified | Uncertain significance (Nov 14, 2024) | ||
| 4-153703386-A-G | not specified | Uncertain significance (Aug 04, 2024) | ||
| 4-153703396-T-A | Likely benign (Mar 02, 2018) | |||
| 4-153703412-G-T | not specified | Uncertain significance (Jul 05, 2023) | ||
| 4-153703489-G-C | Hereditary angioedema with normal C1Inh | not provided (Feb 01, 2020) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TLR2 | protein_coding | protein_coding | ENST00000260010 | 1 | 4200 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00000102 | 0.937 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.407 | 380 | 403 | 0.943 | 0.0000202 | 5175 |
| Missense in Polyphen | 134 | 146.32 | 0.9158 | 1978 | ||
| Synonymous | 0.936 | 144 | 159 | 0.906 | 0.00000791 | 1508 |
| Loss of Function | 1.80 | 13 | 22.1 | 0.587 | 0.00000111 | 318 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides (PubMed:21078852, PubMed:17889651). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins (PubMed:10426995, PubMed:10426996). 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 TLR6 (PubMed:11441107). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4 (PubMed:16622205). MAPK activation in response to bacterial peptidoglycan also occurs via this receptor (PubMed:16622205). Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression (PubMed:15809303). Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse) (By similarity). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides (PubMed:16880211). Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (By similarity). {ECO:0000250|UniProtKB:Q9QUN7, ECO:0000269|PubMed:10426995, ECO:0000269|PubMed:10426996, ECO:0000269|PubMed:11441107, ECO:0000269|PubMed:15809303, ECO:0000269|PubMed:16622205, ECO:0000269|PubMed:16880211, ECO:0000269|PubMed:17889651, ECO:0000269|PubMed:19362712, ECO:0000269|PubMed:21078852}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Legionellosis - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Phagosome - Homo sapiens (human);Amoebiasis - 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);Leishmaniasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Human Complement System;IL1 and megakaryocytes in obesity;Toll-like Receptor Signaling;Simplified Depiction of MYD88 Distinct Input-Output Pathway;ApoE and miR-146 in inflammation and atherosclerosis;PI3K-Akt Signaling Pathway;Toll-like Receptor Signaling Pathway;Neutrophil degranulation;nfkb activation by nontypeable hemophilus influenzae;toll-like receptor pathway;Toll-Like Receptors Cascades;Antimicrobial peptides;Innate Immune System;Immune System;Adaptive Immune System;Beta defensins;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;Defensins;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
- 0.705
Intolerance Scores
- loftool
- rvis_EVS
- -0.15
- rvis_percentile_EVS
- 42.28
Haploinsufficiency Scores
- pHI
- 0.244
- hipred
- N
- hipred_score
- 0.313
- ghis
- 0.517
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.537
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tlr2
- Phenotype
- normal 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- response to hypoxia;microglial cell activation;cell activation;toll-like receptor signaling pathway;cytokine secretion involved in immune response;MyD88-dependent toll-like receptor signaling pathway;leukotriene metabolic process;apoptotic process;inflammatory response;immune response;signal transduction;I-kappaB phosphorylation;learning;negative regulation of cell population proliferation;response to toxic substance;positive regulation of gene expression;microglia development;positive regulation of Wnt signaling pathway;lipopolysaccharide-mediated signaling pathway;central nervous system myelin formation;response to progesterone;interleukin-10 production;tumor necrosis factor production;positive regulation of chemokine 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;response to insulin;positive regulation of toll-like receptor signaling pathway;toll-like receptor 2 signaling pathway;toll-like receptor TLR1:TLR2 signaling pathway;toll-like receptor TLR6:TLR2 signaling pathway;detection of triacyl bacterial lipopeptide;detection of diacyl bacterial lipopeptide;neutrophil degranulation;innate immune response;positive regulation of transcription by RNA polymerase II;nitric oxide metabolic process;positive regulation of oligodendrocyte differentiation;positive regulation of inflammatory response;negative regulation of phagocytosis;defense response to Gram-positive bacterium;positive regulation of NF-kappaB transcription factor activity;positive regulation of nitric-oxide synthase biosynthetic process;negative regulation of synapse assembly;response to fatty acid;cellular response to bacterial lipopeptide;cellular response to lipoteichoic acid;cellular response to interferon-gamma;cellular response to diacyl bacterial lipopeptide;cellular response to triacyl bacterial lipopeptide;positive regulation of NIK/NF-kappaB signaling;positive regulation of cellular response to macrophage colony-stimulating factor stimulus;positive regulation of interleukin-8 secretion
- Cellular component
- cytoplasm;Golgi apparatus;plasma membrane;integral component of plasma membrane;cell surface;secretory granule membrane;phagocytic vesicle membrane;intrinsic component of plasma membrane;Toll-like receptor 1-Toll-like receptor 2 protein complex;cell projection;cell body;membrane raft
- Molecular function
- lipopolysaccharide binding;amyloid-beta binding;lipopolysaccharide receptor activity;protein binding;signaling pattern recognition receptor activity;Toll-like receptor binding;signaling receptor activity;triacyl lipopeptide binding;identical protein binding;peptidoglycan binding;protein-containing complex binding;protein heterodimerization activity