MAPT

Microtubule-associated protein tau UniProt accession P10636

Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome.

The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization

Source: UniProt

Interacts with MARK1, MARK2, MARK3 and MARK4 (PubMed:23666762). Interacts with PSMC2 through SQSTM1 (By similarity). Interacts with SQSTM1 when polyubiquitinated (PubMed:15953362).

Interacts with FKBP4 (By similarity). Binds to CSNK1D (PubMed:14761950). Interacts with SGK1 (PubMed:16982696).

Interacts with EPM2A; the interaction dephosphorylates MAPT at Ser-396 (PubMed:19542233). Interacts with PIN1 (PubMed:11313338). Interacts with LRRK2 (PubMed:26014385).

Interacts with LRP1, leading to endocytosis; this interaction is reduced in the presence of LRPAP1/RAP (PubMed:32296178)

Source: UniProt
Cytoplasm, cytosol, Cell membrane — Peripheral membrane protein, Cytoplasm, cytoskeleton, Cell projection, axon, Cell projection, dendrite, Secreted
Source: UniProt

Expressed in neurons. Isoform PNS-tau is expressed in the peripheral nervous system while the others are expressed in the central nervous system

Source: UniProt

The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats

Source: UniProt
  • Unknown disease
  • Frontotemporal dementia 1 (FTD1)

    A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala.

    In most cases, protein tau deposits are found in glial cells and/or neurons.

  • Pick disease of the brain (PIDB)

    A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration.

  • Unknown disease
  • Progressive supranuclear palsy 1 (PSNP1)

    Characterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions.

    Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance; genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613.

  • Parkinson-dementia syndrome (PARDE)

    A syndrome characterized by parkinsonism, tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei.

Source: UniProt
  • Caspase-mediated cleavage of cytoskeletal proteins
  • Activation of AMPK downstream of NMDARs
  • PKR-mediated signaling
Source: Reactome via UniProt

Mutations

No mutation information available.

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to MAPT, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 51

NCT ID Condition Brief Title Phase Status
NCT04305210 Alzheimer's Disease Alzheimer's Disease: Clinical Investigation and Neuroimage Studies Including 18F-PM-PBB3 and 18F-florbetapir (AV-45) PET Examination PHASE2 UNKNOWN
NCT03545789 Healthy Volunteers, Alzheimer Disease, Progressive Supranuclear Palsy Phase 1 Test-retest Evaluation of [18F]MNI-958 PET PHASE1 COMPLETED
NCT05942404 POCD - Postoperative Cognitive Dysfunction, Mechanical Bowel Preparation Investigation of the Effect of Preoperative Bowel Cleansing on Postoperative Cognitive Impairment NA COMPLETED
NCT07498426 Progressive Supranuclear Palsy Richardson Syndrome (PSP-RS) A Study to Evaluate the Efficacy of NIO752 in Participants With Progressive Supranuclear Palsy PHASE3 NOT_YET_RECRUITING
NCT00978536 Disseminated Sclerosis A Monocenter, Cross-sectional Study to Compare Different Type of Cognitive Impairment in Multiple Sclerosis Patients and Cerebrospinal Fluid Biomarkers (Beta Amyloid, Total Tau Protein and Tau-phosphorylated Protein). NA TERMINATED
NCT03430869 Major Depressive Disorder Pathophysiology of Neurodegeneration in Late-life Depression (AV45+THK) PHASE2 COMPLETED
NCT07458620 Alzheimer's Disease (AD) Prospective Single-Arm Safety Study of Cervical LVA in AD Patients PHASE1 NOT_YET_RECRUITING
NCT04363684 Frontotemporal Lobar Degeneration (FTLD), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), Behavioral Variant Frontotemporal Dementia (bvFTD), Semantic Variant Primary Progressive Aphasia (svPPA), Nonfluent Variant Primary Progressive Aphasia (nfvPPA), FTD With Amyotrophic Lateral Sclerosis (FTD/ALS), Amyotrophic Lateral Sclerosis, Oligosymptomatic PSP (oPSP), C9orf72, GRN Related Frontotemporal Dementia, MAPT Gene Mutation, TBK1 Gene Mutation, Oligosymptomatic Progressive Supranuclear Palsy ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) N/A RECRUITING
NCT02531360 Alzheimer's Disease (AD), Progressive Supranuclear Palsy (PSP), Cortical Basal Syndrome (CBS), Frontal Temporal Dementia (FTD) Evaluation of [18F]MNI-815 as a Potential PET Radioligand for Imaging Tau Protein in the Brain of Patients With Tauopathies EARLY_PHASE1 COMPLETED
NCT05464355 Delirium, Postoperative Cognitive Dysfunction, Cognitive Decline, Cognitive Impairment Biomarkers Associated With Postoperative Cognitive Dysfunction N/A ACTIVE_NOT_RECRUITING