The [MAPT](/proteins/tau) (Microtubule-Associated Protein Tau) gene encodes the tau protein, which plays a critical role in microtubule stabilization and neuronal function. Mutations in MAPT are a major cause of frontotemporal dementia and related neurodegenerative disorders, including Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD). [@hutton1998][@spillantini1998]
Gene Overview
| Property | Value | |----------|-------| | Gene Symbol | MAPT | | Full Name | Microtubule-Associated Protein Tau | | Chromosomal Location | 17q21.31 | | NCBI Gene ID | 4137 | | OMIM | [157140](https://www.omim.org/entry/157140) | | Ensembl ID | ENSG00000186868 | | UniProt ID | [P10636](https://www.uniprot.org/uniprotkb/P10636) | | Inheritance | Autosomal Dominant | | Exons | 16 (major isoform transcripts) | | Protein Length | 352-441 amino acids (6 isoforms) |
Function
The MAPT gene produces the tau protein, which is primarily expressed in [neurons](/entities/neurons). Tau functions to:
Stabilize microtubules: Tau binds to microtubules and promotes their assembly and stability, essential for axonal transport
Regulate axonal transport: By modulating microtubule dynamics, tau facilitates the trafficking of organelles and vesicles along axons
Signal transduction: Tau interacts with various signaling molecules and participates in neuronal signaling pathways [@ballatore2007][@leybns2022]
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MAPT Gene Variants and Mutations
The [MAPT](/proteins/tau) (Microtubule-Associated Protein Tau) gene encodes the tau protein, which plays a critical role in microtubule stabilization and neuronal function. Mutations in MAPT are a major cause of frontotemporal dementia and related neurodegenerative disorders, including Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD). [@hutton1998][@spillantini1998]
Gene Overview
| Property | Value | |----------|-------| | Gene Symbol | MAPT | | Full Name | Microtubule-Associated Protein Tau | | Chromosomal Location | 17q21.31 | | NCBI Gene ID | 4137 | | OMIM | [157140](https://www.omim.org/entry/157140) | | Ensembl ID | ENSG00000186868 | | UniProt ID | [P10636](https://www.uniprot.org/uniprotkb/P10636) | | Inheritance | Autosomal Dominant | | Exons | 16 (major isoform transcripts) | | Protein Length | 352-441 amino acids (6 isoforms) |
Function
The MAPT gene produces the tau protein, which is primarily expressed in [neurons](/entities/neurons). Tau functions to:
Stabilize microtubules: Tau binds to microtubules and promotes their assembly and stability, essential for axonal transport
Regulate axonal transport: By modulating microtubule dynamics, tau facilitates the trafficking of organelles and vesicles along axons
Signal transduction: Tau interacts with various signaling molecules and participates in neuronal signaling pathways [@ballatore2007][@leybns2022]
The tau protein has six isoforms ranging from 352 to 441 amino acids, generated by alternative splicing of exons 2, 3, and 10. Inclusion of exon 10 results in 3-repeat (3R) tau isoforms, while exclusion produces 4-repeat (4R) isoforms. The 4R/3R balance is critical for normal neuronal function. [@wang2024]
Disease Associations
Mutations in MAPT cause a group of clinically and pathologically heterogeneous disorders collectively termed frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). These include: [@ghetti2015]
Frontotemporal Dementia (FTD) — The most common cause of early-onset dementia, characterized by behavioral changes and language impairment
Progressive Supranuclear Palsy (PSP) — A disorder causing vertical gaze palsy, parkinsonism, and cognitive decline [@spillantini1998]
Corticobasal Degeneration (CBD) — Features include asymmetric rigidity, apraxia, and cortical sensory loss
Pick's Disease — A form of FTD with characteristic Pick bodies (tau inclusions)
MAPT H1 Haplotype
The MAPT gene exists in two major haplotypes: H1 and H2. The H1 haplotype is the ancestral form and is strongly associated with increased risk of PSP and CBD. The H1 haplotype spans a region including the MAPT gene and surrounding sequences, creating specific linkage disequilibrium patterns. [@caim2022]
H1/H1 genotype: Increases risk of PSP by 3-5 fold, CBD by 2-3 fold
H2 haplotype: More common in European populations, associated with reduced PSP risk