MAPT Gene: Function, Mutations, and Associated Diseases | Tau Protein

The MAPT gene encodes the microtubule-associated protein tau, which is predominantly expressed in neurons and plays a critical role in microtubule assembly and stabilization. Tau protein undergoes alternative splicing to produce six major isoforms in the adult human brain, differing by the presence of zero, one, or two N-terminal inserts and three or four microtubule-binding repeats. Pathogenic variants in MAPT are associated with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and other tauopathies, including Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration. Tau pathology is characterized by hyperphosphorylation, aggregation, and formation of neurofibrillary tangles.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Alzheimer's disease pathway (KEGG hsa05010)

• Tauopathies (Reactome R-HSA-8863795)

• Microtubule cytoskeleton regulation (Reactome R-HSA-190840)

• Axonal transport (Reactome R-HSA-190828)

The MAPT gene encodes tau, a microtubule-associated protein that promotes microtubule assembly and stability. Tau is predominantly expressed in neurons, particularly in axons. Alternative splicing generates six isoforms in the CNS, which differ by the presence of 0, 1, or 2 N-terminal inserts and 3 or 4 microtubule-binding repeats (3R/4R). Tau is a phosphoprotein; hyperphosphorylation reduces its affinity for microtubules and leads to aggregation into paired helical filaments, a hallmark of Alzheimer's disease and other tauopathies. Pathogenic mutations in MAPT cause frontotemporal dementia with parkinsonism-17 (FTDP-17) by altering tau splicing or function. The protein is also involved in signal transduction, synaptic plasticity, and DNA protection under stress.