TLR8
protein-codingtoll like receptor 8, 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 gene is predominantly expressed in lung and peripheral blood leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0024777
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0024777
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: Individuals may be susceptible to infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TLR8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138636.5. 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 | 6 | 6 | 3 | 15 | ||
| missense | 4 | 1 | 100 | 8 | 1 | 114 |
| nonsense | 3 | 3 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 4 | 2 | 114 | 14 | 4 | 138 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_619542.1 | 2 | MANE Select | |
| Ensembl | ENSP00000218032.7 | 2 | MANE Select | |
| RefSeq | NP_057694.2 | 2 | Standard | |
| Ensembl | ENSP00000312082.5 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Toll-like receptor signaling pathway - 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
Biological Process
- microglial cell activation
- regulation of protein phosphorylation
- toll-like receptor signaling pathway
- MyD88-dependent toll-like receptor signaling pathway
- immune response
Molecular Function
- DNA binding
- RNA binding
- double-stranded RNA binding
- single-stranded RNA binding
- transmembrane signaling receptor activity
Cellular Component
- Golgi membrane
- endoplasmic reticulum membrane
- plasma membrane
- external side of plasma membrane
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000218032
- Coding exons
- 2
- Length
- 16550
- Individuals with no LoFs
- 125679
- Homozygous LoFs
- 5
- Heterozygous LoFs
- 8
- Defined
- 125692
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.08 | 218 | 389 | 0.560 | 0.0000300 | 6923 |
| Missense (PolyPhen) | 31 | 121.33 | 0.2555 | 2399 | ||
| Synonymous | -0.0189 | 154 | 154 | 1.00 | 0.0000118 | 2003 |
| Loss of Function | 3.31 | 5 | 21.6 | 0.231 | 0.00000171 | 410 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000076 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00027 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00019 | 0.00014 | rare |
| European (Non-Finnish) | 0.000074 | 0.000053 | rare |
| South Asian | 0.000053 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. {ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:23520111}.;
Recessive Scores
- pRec
- 0.193
Intolerance Scores
- LoFtool
- 0.288
- RVIS EVS
- -0.24
- RVIS percentile EVS
- 36.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.962
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |