| BTK | |
|---|---|
| Gene | [BTK](/genes/btk) |
| UniProt ID | [Q06187](https://www.uniprot.org/uniprot/Q06187) |
| Molecular Weight | 76 kDa |
| Subcellular Localization | Cytoplasm, plasma membrane |
| Protein Family | Tec family tyrosine kinase |
| Disease | X-linked agammaglobulinemia |
BTK (Bruton's Tyrosine Kinase) is a non-receptor tyrosine kinase belonging to the Tec family. The BTK gene encodes a 659-amino acid protein originally characterized for its essential role in B cell receptor signaling and B cell development. Recently, BTK has emerged as a significant player in neuroinflammation and neurodegenerative diseases.
BTK contains multiple functional domains:
| Domain | Position | Function |
|---|---|---|
| PH domain | N-terminal | Phosphoinositide binding, membrane localization |
| TH domain | Proline-rich | Proline-rich motifs for SH3 interactions |
| SH3 domain | Middle | Protein-protein interactions |
| SH2 domain | Middle | Phosphotyrosine binding |
| Kinase domain | C-terminal | Catalytic tyrosine kinase activity |
BTK is essential for B cell development:
BTK activates multiple downstream pathways:
BTK is expressed in:
BTK in microglia contributes to AD pathogenesis:
BTK inhibitors show promise:
FDA-approved and experimental BTK inhibitors:
| Drug | Status | Indication |
|---|---|---|
| Ibrutinib | Approved | CLL, MCL, Waldenstrom |
| Acalabrutinib | Approved | CLL, MCL |
| Evobrutinib | Phase 3 | MS |
| Rilzabrutinib | Phase 3 | ITP, MS |
BTK inhibitors in development for:
Microglial BTK contributes to:
Current BTK inhibitor trials for neurodegeneration:
| Trial | Compound | Phase | Indication |
|---|---|---|---|
| HERO | Evobrutinib | Phase 3 | MS |
| Evolution | Tolebrutinib | Phase 3 | MS |
| NCT04848260 | Fenebrutinib | Phase 2 | MS |
| NCT04681833 | BIIB091 | Phase 1 | AD |
BTK inhibitor side effects: