TOLLIP: Toll Interacting Protein – Key Regulator of Innate Immunity and Inflammation
Comprehensive gene card for TOLLIP, including genomic data, expression, mutations, and disease associations.
Gene Information Card
| Symbol | TOLLIP |
|---|---|
| Full Name | toll interacting protein |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 54472 ncbi.nlm.nih.gov/gene/54472 |
| Ensembl ID | ENSG00000149418 |
| UniProt ID | Q9H0E2 |
| OMIM ID | 606296 |
| HGNC ID | 16476 |
| Aliases | IL-1RAcPIP, TOLLIP1 |
Description
TOLLIP (toll interacting protein) encodes a ubiquitin-binding protein that negatively regulates Toll-like receptor (TLR) signaling by interacting with the cytoplasmic domain of TLRs and the interleukin-1 receptor-associated kinase (IRAK) complex. It is involved in innate immune responses, inflammation, and autophagy. The gene is located on chromosome 11p15.5 and is expressed in multiple tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tuberculosis | TOLLIP polymorphisms affect TLR signaling and autophagy, influencing susceptibility to Mycobacterium tuberculosis. | ClinVar, NCBI |
| Asthma | Variants in TOLLIP are associated with altered TLR2/4 signaling and airway inflammation. | ClinVar, NCBI |
| Inflammatory bowel disease | TOLLIP expression changes modulate NF-κB activation and cytokine production in intestinal epithelium. | NCBI, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Spleen | 15.2 | Medium |
| Whole blood | 8.1 | Low |
| Liver | 10.3 | Medium |
| Kidney | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.0 | Embryonic kidney cells |
| HeLa | 11.2 | Cervical cancer cells |
| THP-1 | 18.5 | Monocytic leukemia cells |
| A549 | 13.8 | Lung carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs5743899 | SNP | 0.15 (global) | Intronic variant associated with tuberculosis susceptibility |
| rs5743854 | SNP | 0.10 (global) | Missense variant (p.Arg105Cys) affecting protein function |
| c.1A>G | SNP | 0.02 (global) | Start codon loss, likely loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Variants such as c.1A>G and p.Arg105Cys reduce TOLLIP protein expression or disrupt TLR binding, impairing negative regulation of inflammation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TOLLIP.
Dominant Negative (DN)
No dominant-negative mutations described for TOLLIP.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • cytoplasm (GO:0005737) |
| • endosome (GO:0005768) | • autophagy (GO:0006914) |
| • negative regulation of NF-κB transcription factor activity (GO:0032088) | • negative regulation of I-kappaB kinase/NF-κB signaling (GO:0043124) |
| • innate immune response (GO:0045087) |
Pathways
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• NF-kappa B signaling pathway (KEGG: hsa04064)
• Autophagy (KEGG: hsa04140)
Protein Summary
TOLLIP is a 274-amino-acid protein containing a C2 domain and a ubiquitin-binding domain. It acts as a negative regulator of TLR signaling by recruiting IRAK1 to the TLR complex and promoting its ubiquitination and degradation. TOLLIP also participates in autophagy by facilitating the delivery of ubiquitinated cargo to autophagosomes. Its expression is ubiquitous, with highest levels in immune tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOLLIP Knockout HEK293 Cell Line | EDJ-KQ11428 | Human | 54472 | Details Get a Quote |
| TOLLIP Knockout A-549 Cell Line | EDJ-KQ38346 | Human | 54472 | Details Get a Quote |
| TOLLIP Knockout HCT 116 Cell Line | EDJ-KQ39682 | Human | 54472 | Details Get a Quote |
| TOLLIP Knockout HeLa Cell Line | EDJ-KQ39683 | Human | 54472 | Details Get a Quote |
| Tollip Knockout MPC-5 Cell Line | EDJ-KZ58 | Mouse | 54473 | Details Get a Quote |
