| TYROBP — TYRO Binding Protein | |
|---|---|
| Symbol | TYROBP |
| Full Name | TYRO Protein Tyrosine Kinase Binding Protein (DAP12) |
| Chromosome | 19q13.12 |
| NCBI Gene | 7305 |
| Ensembl | ENSG00000111653 |
| OMIM | 605712 |
| UniProt | Q9Y241 |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers), [Frontotemporal Dementia](/diseases/ftd), [Nasu-Hakola Disease](/diseases/nasu-hakola-disease) |
| Expression | [Microglia](/cell-types/microglia-neuroinflammation), Monocytes, NK cells, Osteoclasts |
Tyrobp — Tyro Binding Protein (Dap12) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
TYROBP (TYRO Protein Tyrosine Kinase Binding Protein, also known as DAP12) is a gene located on chromosome 19q13.12 that encodes a transmembrane signaling adaptor protein. TYROBP/DAP12 is a critical component of the innate immune signaling pathway, associating with multiple activating receptors on microglia and other immune cells to regulate inflammatory responses in the brain[1].
TYROBP forms a signaling complex with TREM2 and other triggering receptors, making it essential for microglial function in neurodegenerative disease contexts. Mutations in TYROBP cause a form of Nasu-Hakola disease (PLOSL), characterized by early-onset dementia and bone cysts.
TYROBP/DAP12 serves as a signaling adaptor protein with the following characteristics:
In microglia, TYROBP partners with several critical receptors:
Biallelic loss-of-function mutations in TYROBP cause a recessive form of Nasu-Hakola disease (PLOSL1):
TYROBP genetic variants influence Alzheimer's Disease risk:
TYROBP is implicated in FTD pathogenesis:
The TYROBP-TREM2 signaling axis is a major therapeutic target:
The study of Tyrobp — Tyro Binding Protein (Dap12) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.