TICAM1
TIR Domain Containing Adaptor Molecule 1
Gene Information Card
| Symbol | TICAM1 |
|---|---|
| Full Name | TIR Domain Containing Adaptor Molecule 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 148022 ncbi.nlm.nih.gov/gene/148022 |
| Ensembl ID | ENSG00000127666 |
| UniProt ID | Q8IUC6 |
| OMIM ID | 607601 |
| HGNC ID | 18348 |
| Aliases | TRIF, MyD88-3, TICAM-1, PRO2165 |
Description
TICAM1 encodes the TIR-domain-containing adaptor molecule 1 (TRIF), a key adaptor protein in the Toll-like receptor (TLR) signaling pathway. TRIF mediates MyD88-independent signaling downstream of TLR3 and TLR4, leading to activation of IRF3 and NF-kB transcription factors, which induce type I interferons and pro-inflammatory cytokines. This gene is critical for antiviral and antibacterial innate immune responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Herpes simplex encephalitis | Deficient TLR3-TRIF signaling impairs interferon production, increasing susceptibility to HSV-1 infection in the CNS. | PMID: 21217753, ClinVar |
| Primary immunodeficiency with susceptibility to viral infections | Loss-of-function mutations in TICAM1 impair interferon induction, leading to severe viral illnesses. | PMID: 21217753, OMIM |
| Influenza susceptibility | Impaired TRIF function reduces antiviral responses, increasing risk of severe influenza. | PMID: 25944712 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 2.1 | Low |
| Spleen | 1.8 | Low |
| Whole blood | 1.5 | Low |
| Brain | 0.9 | Not detected |
| Liver | 0.7 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.5 | Low expression |
| THP-1 | 1.2 | Monocyte line, moderate |
| A549 | 0.8 | Lung epithelial, low |
| Jurkat | 0.3 | T-cell line, very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1660C>T (p.Arg554*) | Nonsense | Rare | Loss of function; truncation of TRIF protein |
| c.1174C>T (p.Arg392*) | Nonsense | Rare | Loss of function; impaired TLR3 signaling |
| c.2155C>T (p.Arg719Trp) | Missense | Rare | Reduced IRF3 activation |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg554*, p.Arg392*) result in truncated, non-functional TRIF protein, impairing TLR3/TLR4 signaling and interferon production.
Gain of Function (GOF)
No gain-of-function mutations are currently reported in TICAM1.
Dominant Negative (DN)
Some missense variants may act in a dominant-negative manner by interfering with wild-type TRIF function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005737 (cytoplasm) | • GO:0005829 (cytosol) |
| • GO:0035662 (Toll-like receptor 4 binding) | • GO:0035663 (Toll-like receptor 3 binding) |
| • GO:0042802 (identical protein binding) | • GO:0007165 (signal transduction) |
| • GO:0034138 (toll-like receptor 3 signaling pathway) | • GO:0034142 (toll-like receptor 4 signaling pathway) |
| • GO:0045087 (innate immune response) | • GO:0060333 (type I interferon production) |
Pathways
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• RIG-I-like receptor signaling pathway (KEGG: hsa04622)
• Cytosolic DNA-sensing pathway (KEGG: hsa04623)
• TRIF-dependent TLR signaling (Reactome: R-HSA-166016)
Protein Summary
The TICAM1 protein, also known as TRIF, is a 712-amino acid adaptor molecule containing an N-terminal TIR domain, a central proline-rich region, and a C-terminal RHIM motif. It interacts with TLR3 and TLR4 via TIR-TIR interactions, recruiting downstream kinases TBK1 and IKKε to phosphorylate IRF3, and also activates NF-kB via TRAF6. TRIF is essential for the MyD88-independent arm of TLR signaling, leading to type I interferon production and inflammatory cytokine expression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TICAM1 Knockout HEK293 Cell Line | EDJ-KQ593 | Human | 148022 | Details Get a Quote |
| TICAM1 Knockout HeLa Cell Line | EDJ-KQ18035 | Human | 148022 | Details Get a Quote |
| TICAM1 Knockout A-549 Cell Line | EDC07592 | Human | 148022 | Details Get a Quote |
| TICAM1 Knockout HCT 116 Cell Line | EDJ-KQ19030 | Human | 148022 | Details Get a Quote |
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