TBK1 (TANK-Binding Kinase 1): Gene, Function, and Disease Associations
A comprehensive overview of the TBK1 gene, including its genomic context, protein function, expression patterns, mutations, and clinical significance.
Gene Information Card
| Symbol | TBK1 |
|---|---|
| Full Name | TANK-binding kinase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q14.2 |
| NCBI Gene ID | 29110 ncbi.nlm.nih.gov/gene/29110 |
| Ensembl ID | ENSG00000183747 |
| UniProt ID | Q9UHD2 |
| OMIM ID | 604834 |
| HGNC ID | 11584 |
| Aliases | NAK, T2K, FTDALS4 |
Description
The TBK1 gene encodes TANK-binding kinase 1, a serine/threonine kinase that plays a critical role in innate immune signaling, particularly in the Toll-like receptor (TLR) and RIG-I-like receptor (RLR) pathways. It phosphorylates and activates IRF3 and IRF7, leading to type I interferon production. TBK1 also regulates autophagy and is involved in cell proliferation and survival. Mutations in TBK1 are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic lateral sclerosis (ALS) | Loss-of-function mutations impair autophagy and innate immune signaling, leading to neurodegeneration. | ClinVar, OMIM |
| Frontotemporal dementia (FTD) | Haploinsufficiency or dominant-negative effects disrupt TBK1-mediated neuroprotection. | ClinVar, OMIM |
| Primary open-angle glaucoma (POAG) | Rare variants may affect TBK1 copy number, influencing disease risk. | OMIM, ClinVar |
| Viral infections (e.g., influenza) | TBK1 is essential for antiviral interferon response; mutations may increase susceptibility. | UniProt, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.4 | Medium |
| Spleen | 11.8 | Medium |
| Blood | 10.2 | Medium |
| Brain | 8.5 | Low |
| Liver | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical carcinoma; high expression |
| A549 | 13.8 | Lung carcinoma; moderate-high |
| HEK293 | 12.1 | Embryonic kidney; moderate |
| K562 | 9.5 | Leukemia; low-moderate |
| MCF7 | 8.7 | Breast carcinoma; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg47His | Missense | 0.01% (gnomAD) | Impaired kinase activity; associated with ALS |
| p.Leu33Phe | Missense | 0.005% | Reduced autophosphorylation; ALS-linked |
| p.Glu696Lys | Missense | 0.02% | Disrupts protein-protein interactions; FTD |
| c.1365_1366delAG | Frameshift | Rare | Loss-of-function; ALS/FTD |
| p.Arg228His | Missense | 0.008% | Altered substrate specificity; glaucoma |
Mutation functional classification
Loss of Function (LOF)
Many ALS/FTD mutations are loss-of-function, leading to reduced kinase activity or protein stability, impairing autophagy and immune signaling.
Gain of Function (GOF)
Some rare variants may exhibit gain-of-function effects, but evidence is limited; mainly implicated in cancer contexts.
Dominant Negative (DN)
Certain missense mutations can act in a dominant-negative manner, interfering with wild-type TBK1 function in oligomeric complexes.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • protein kinase activity | • signal transducer activity |
| • identical protein binding | • autophagy |
| • innate immune response | • type I interferon production |
| • cytoplasm | • nucleus |
Pathways
• Toll-like receptor signaling pathway
• RIG-I-like receptor signaling pathway
• Cytosolic DNA-sensing pathway
• Autophagy pathway
• NF-kappa B signaling pathway
Protein Summary
TBK1 is a 729-amino acid protein with an N-terminal kinase domain, a ubiquitin-like domain, and a C-terminal coiled-coil domain. It forms homodimers and interacts with TANK, TBKBP1, and other adaptors. The kinase phosphorylates IRF3/7 and also phosphorylates optineurin (OPTN) to regulate autophagy. TBK1 is ubiquitously expressed and is a key node in innate immunity and selective autophagy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TTBK1 Knockout HEK293 Cell Line | EDJ-KQ10137 | Human | 84630 | Details Get a Quote |
| TBK1 Knockout HEK293 Cell Line | EDJ-KQ17906 | Human | 29110 | Details Get a Quote |
| TBK1 Knockout A-549 Cell Line | EDJ-KQ19269 | Human | 29110 | Details Get a Quote |
| TBK1 Knockout HCT 116 Cell Line | EDJ-KQ20629 | Human | 29110 | Details Get a Quote |
| TBK1 Knockout HeLa Cell Line | EDJ-KQ20630 | Human | 29110 | Details Get a Quote |
| Tbk1 Knockout RAW 264.7 Cell Line | EDJ-KZ50 | Mouse | 56480 | Details Get a Quote |
| TTBK1 Knockout HeLa Cell Line | EDJ-KQ57623 | Human | 84630 | Details Get a Quote |
| TTBK1 Knockout A-549 Cell Line | EDJ-KQ66121 | Human | 84630 | Details Get a Quote |
| TTBK1 Knockout HCT 116 Cell Line | EDJ-KQ74546 | Human | 84630 | Details Get a Quote |
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