TLR1
protein-codingtoll like receptor 1, 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 ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [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 ~69.3 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 TLR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003263.4. 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 | 11 | 3 | 14 | |||
| missense | 2 | 113 | 11 | 4 | 130 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 2 | 0 | 114 | 22 | 7 | 145 |
Highest pathogenic variant AF is 0.0006374635
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003254.2 | 1 | MANE Select | |
| Ensembl | ENSP00000354932.2 | 1 | MANE Select | |
| Ensembl | ENSP00000421259.1 | 1 | Standard | |
| Ensembl | ENSP00000421259.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Toll-like receptor signaling pathway - Homo sapiens (human)
- Tuberculosis - Homo sapiens (human)
- Regulation of toll-like receptor signaling pathway
- IL1 and megakaryocytes in obesity
- Toll-like Receptor Signaling
Biological Process
- cell activation
- toll-like receptor signaling pathway
- MyD88-dependent toll-like receptor signaling pathway
- inflammatory response
- immune response
Molecular Function
- transmembrane signaling receptor activity
- protein binding
- Toll-like receptor 2 binding
- signaling receptor activity
- identical protein binding
Cellular Component
- Golgi apparatus
- plasma membrane
- integral component of plasma membrane
- membrane
- phagocytic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308979
- Coding exons
- 1
- Length
- 66141
- Individuals with no LoFs
- 125251
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 493
- Defined
- 125746
- p
- 0.00197
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.702 | 435 | 396 | 1.10 | 0.0000194 | 5247 |
| Missense (PolyPhen) | 146 | 122.09 | 1.1958 | 1746 | ||
| Synonymous | -0.827 | 167 | 154 | 1.08 | 0.00000800 | 1456 |
| Loss of Function | -1.73 | 29 | 20.6 | 1.41 | 8.75e-7 | 318 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.0013 | 0.0011 | notable |
| Ashkenazi Jewish | 0.0082 | 0.0079 | notable |
| East Asian | 0.0019 | 0.0019 | notable |
| Finnish | 0.0018 | 0.0018 | notable |
| European (Non-Finnish) | 0.0018 | 0.0015 | notable |
| South Asian | 0.0035 | 0.0034 | notable |
| Other | 0.0029 | 0.0026 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Participates in the innate immune response to microbial agents. Specifically recognizes diacylated and triacylated lipopeptides. Cooperates with TLR2 to mediate the innate immune response to bacterial lipoproteins or lipopeptides (PubMed:21078852). Forms the activation cluster TLR2:TLR1:CD14 in response to triacylated lipopeptides, 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. {ECO:0000269|PubMed:16880211, ECO:0000269|PubMed:21078852}.;
Recessive Scores
- pRec
- 0.354
Intolerance Scores
- LoFtool
- 0.963
- RVIS EVS
- 1.32
- RVIS percentile EVS
- 94.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.210
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |