TIRAP Gene - TIR Domain Containing Adaptor Protein
Key adaptor in TLR signaling and innate immunity
Gene Information Card
| Symbol | TIRAP |
|---|---|
| Full Name | TIR domain containing adaptor protein |
| Gene Type | protein-coding |
| Chromosomal Location | 11q24.2 |
| NCBI Gene ID | 114609 ncbi.nlm.nih.gov/gene/114609 |
| Ensembl ID | ENSG00000150455 |
| UniProt ID | P58753 |
| OMIM ID | 606252 |
| HGNC ID | 17192 |
| Aliases | MyD88-2, MyD88 adaptor-like, MAL, TIRAP |
Description
TIRAP (TIR domain containing adaptor protein) encodes an adaptor protein involved in Toll-like receptor (TLR) signaling pathways. It bridges TLR2 and TLR4 to the downstream adaptor MyD88, facilitating activation of NF-κB and MAP kinases. TIRAP is essential for innate immune responses to bacterial lipoproteins and lipopolysaccharide.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Meningococcal disease | Defective TIRAP impairs TLR4 signaling, reducing immune response to Neisseria meningitidis | ClinVar, PMID: 16818632 |
| Tuberculosis susceptibility | TIRAP variants (e.g., S180L) modulate TLR2 signaling and risk of Mycobacterium tuberculosis infection | ClinVar, PMID: 16818632 |
| Sepsis | Altered TIRAP expression affects TLR4-mediated cytokine production in sepsis | ClinVar, PMID: 20037584 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 11.8 | Medium |
| Lung | 8.2 | Medium |
| Bone marrow | 7.9 | Medium |
| Whole blood | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.3 | High expression |
| HEK293 (embryonic kidney) | 4.1 | Low expression |
| HeLa (cervical) | 3.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| S180L (rs8177374) | Missense | 5-10% (European) | Reduced TLR2 signaling, protective against some infections but increased risk for others |
| C197Y | Missense | Rare | Impaired TIRAP function, associated with meningococcal disease |
Mutation functional classification
Loss of Function (LOF)
S180L variant reduces TIRAP-mediated TLR2/4 signaling, leading to impaired cytokine production.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported.
Dominant Negative (DN)
C197Y may act as dominant negative by disrupting TIRAP-MyD88 interaction.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• MyD88-dependent cascade (Reactome: R-HSA-166058)
• TIRAP-mediated activation of NF-κB (Reactome: R-HSA-166059)
Protein Summary
TIRAP is a 235-amino acid adaptor protein containing an N-terminal phosphatidylinositol 4,5-bisphosphate (PIP2)-binding domain and a C-terminal TIR domain. It localizes to the plasma membrane and recruits MyD88 to activated TLR2 and TLR4 receptors. TIRAP is critical for initiating innate immune responses against bacterial pathogens.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TIRAP Knockout HEK293 Cell Line | EDJ-KQ594 | Human | 114609 | Details Get a Quote |
| TIRAP Knockout A-549 Cell Line | EDJ-KQ19032 | Human | 114609 | Details Get a Quote |
| TIRAP Knockout HCT 116 Cell Line | EDJ-KQ19033 | Human | 114609 | Details Get a Quote |
| TIRAP Knockout HeLa Cell Line | EDJ-KQ19034 | Human | 114609 | Details Get a Quote |
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