TLR3

toll like receptor 3, the group of CD molecules|Toll like receptors

Basic information

Region (hg38): 4:186068911-186088073

Links

ENSG00000164342NCBI:7098OMIM:603029HGNC:11849Uniprot:O15455AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • immunodeficiency 83, susceptibility to viral infections (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Immunodeficiency 83, susceptibility to viral infectionsAD/ARAllergy/Immunology/InfectiousIndividuals may be susceptible to HSV and other viral infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficialAllergy/Immunology/Infectious17872438; 21911422; 23290562; 25339207; 26513235; 31217193; 32936395

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLR3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLR3 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
4
clinvar
105
clinvar
7
clinvar
116
missense
237
clinvar
9
clinvar
5
clinvar
251
nonsense
9
clinvar
9
start loss
1
clinvar
1
frameshift
11
clinvar
11
inframe indel
2
clinvar
2
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
3
4
2
9
non coding
2
clinvar
14
clinvar
3
clinvar
19
Total 0 0 267 128 15

Variants in TLR3

This is a list of pathogenic ClinVar variants found in the TLR3 region.

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

Position Type Phenotype Significance ClinVar
4-186076613-C-A Herpes simplex encephalitis, susceptibility to, 1 • not specified Benign (Jan 29, 2024)1166908
4-186076620-A-G Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Nov 03, 2022)2988880
4-186076630-CTT-C Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Sep 23, 2022)1973336
4-186076636-C-T Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Nov 01, 2022)1051423
4-186076643-C-T Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Aug 02, 2023)1079617
4-186076651-G-T Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (May 09, 2023)2914462
4-186076652-G-C Herpes simplex encephalitis, susceptibility to, 1 • not specified Uncertain significance (Jan 28, 2023)2150749
4-186076652-G-T Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Apr 10, 2022)2069362
4-186076653-G-C Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Nov 28, 2023)470484
4-186076657-G-A Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Oct 07, 2022)1504695
4-186076657-G-C Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Jun 08, 2022)1980829
4-186076658-C-A Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Sep 27, 2019)1124955
4-186076658-C-T Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Jul 17, 2023)1101924
4-186076663-T-G Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Jan 08, 2024)714646
4-186076680-T-C Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Aug 27, 2023)2972920
4-186076685-A-G Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Jan 22, 2024)1087415
4-186076690-C-T Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Nov 01, 2022)647020
4-186076691-C-T Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Mar 22, 2020)1146308
4-186076705-C-T Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Oct 27, 2023)1018948
4-186076708-T-G Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Dec 25, 2023)3012030
4-186076709-T-C Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Aug 21, 2022)2148502
4-186076722-GCTGACTGCAGCCACCTGAAGTTGA-G Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Jul 19, 2022)1465072
4-186076728-T-C Herpes simplex encephalitis, susceptibility to, 1 Uncertain significance (Jun 20, 2023)956119
4-186076757-C-T Herpes simplex encephalitis, susceptibility to, 1 Likely benign (Jan 31, 2024)2160918
4-186076758-G-A Herpes simplex encephalitis, susceptibility to, 1 • TLR3-related disorder Uncertain significance (Jan 26, 2024)1416387

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TLR3protein_codingprotein_codingENST00000296795 418918
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.63e-70.9921256820661257480.000262
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.5144274580.9320.00002296006
Missense in Polyphen114142.50.81982
Synonymous-0.3111881831.030.000009601725
Loss of Function2.411630.30.5270.00000171379

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005180.000516
Ashkenazi Jewish0.000.00
East Asian0.0007070.000707
Finnish0.00009240.0000924
European (Non-Finnish)0.0002030.000202
Middle Eastern0.0007070.000707
South Asian0.0005560.000555
Other0.000.00

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. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response. {ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043, ECO:0000269|PubMed:16043704, ECO:0000269|PubMed:16144834, ECO:0000269|PubMed:16720699, ECO:0000269|PubMed:16858407, ECO:0000269|PubMed:17178723, ECO:0000269|PubMed:18172197, ECO:0000269|PubMed:22611194}.;
Disease
DISEASE: Encephalopathy, acute, infection-induced, Herpes- specific, 2 (IIAE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:17872438}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.;
Pathway
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Influenza A - Homo sapiens (human);Necroptosis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Toll-like Receptor Signaling;Fibrin Complement Receptor 3 Signaling Pathway;Toll-like Receptor Signaling Pathway;toll-like receptor pathway;TICAM1-dependent activation of IRF3/IRF7;TICAM1, RIP1-mediated IKK complex recruitment ;Toll Like Receptor 3 (TLR3) Cascade;ZBP1(DAI) mediated induction of type I IFNs;Trafficking and processing of endosomal TLR;Toll-Like Receptors Cascades;Innate Immune System;Immune System;RIP-mediated NFkB activation via ZBP1;TLR3-mediated TICAM1-dependent programmed cell death;Cytosolic sensors of pathogen-associated DNA ;Endogenous TLR signaling;TICAM1,TRAF6-dependent induction of TAK1 complex (Consensus)

Recessive Scores

pRec
0.533

Intolerance Scores

loftool
0.780
rvis_EVS
-0.24
rvis_percentile_EVS
36.28

Haploinsufficiency Scores

pHI
0.0933
hipred
Y
hipred_score
0.756
ghis
0.457

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.475

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tlr3
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); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; neoplasm; 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); reproductive system phenotype; 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; muscle phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype;

Gene ontology

Biological process
microglial cell activation;toll-like receptor signaling pathway;regulation of dendritic cell cytokine production;MyD88-independent toll-like receptor signaling pathway;hyperosmotic response;signal transduction;I-kappaB kinase/NF-kappaB signaling;activation of NF-kappaB-inducing kinase activity;I-kappaB phosphorylation;male gonad development;detection of virus;positive regulation of gene expression;positive regulation of chemokine production;positive regulation of interferon-beta production;positive regulation of interleukin-12 production;positive regulation of interleukin-6 production;positive regulation of interleukin-8 production;positive regulation of tumor necrosis factor production;positive regulation of toll-like receptor signaling pathway;negative regulation of MyD88-independent toll-like receptor signaling pathway;toll-like receptor 3 signaling pathway;positive regulation of type III interferon production;cellular response to interferon-beta;TRIF-dependent toll-like receptor signaling pathway;cellular response to drug;defense response to bacterium;positive regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to exogenous dsRNA;positive regulation of interferon-gamma biosynthetic process;positive regulation of chemokine biosynthetic process;innate immune response;positive regulation of interferon-alpha biosynthetic process;positive regulation of interferon-beta biosynthetic process;negative regulation of osteoclast differentiation;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;positive regulation of JNK cascade;positive regulation of inflammatory response;positive regulation of NF-kappaB transcription factor activity;defense response to virus;necroptotic process;cellular response to mechanical stimulus;cellular response to interferon-gamma;cellular response to exogenous dsRNA;apoptotic signaling pathway;extrinsic apoptotic signaling pathway;necroptotic signaling pathway;positive regulation of NIK/NF-kappaB signaling
Cellular component
Golgi membrane;extracellular space;cytoplasm;lysosomal membrane;early endosome;endoplasmic reticulum membrane;integral component of plasma membrane;cell surface;endosome membrane;membrane;extracellular matrix;endolysosome membrane
Molecular function
double-stranded RNA binding;transmembrane signaling receptor activity;protein binding;signaling receptor activity;identical protein binding