Mutations Position Table
MAPT P301 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| P301P |
FTD : Benign | Substitution | Substitution | Silent | Coding | Exon 10 | Patient had severe neuronal loss in the frontal and temporal cortices, globus pallidus, substantia nigra, red nucleus, and dentate nucleus. Tau-positive fibrillar structures in neurons and glia in these regions. The pathology was attributed to the IVS10+11 mutation in MAPT, which the patient also carried. |
No change in the ratio of 3-repeat (3R) to 4-repeat (4R) tau isoforms. |
Miyamoto et al., 2001 |
| P301L |
FTD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 10 | Tau aggregates consisting mainly of 4-repeat (4R) isoforms. Numerous intracytoplasmic tau deposits in neurons and glia in multiple brain regions, including the hippocampus, neocortex, and substantia nigra. Severe neuronal loss, gliosis, and a few ballooned cells in the frontal and temporal cortices. |
Strongly promotes β-sheet formation in 4R tau and accelerates the formation of paired helical filament. Decreases tau's ability to promote microtubule assembly. |
Hutton et al., 1998; Dumanchin et al., 1998; Clark et al., 1998; Spillantini et al., 1998 |
| P301S |
FTD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 10 | Heterogenous. Frontotemporal atrophy and extensive inclusions of hyperphosphorylated tau in neurons and glia. Subcortical regions also affected. |
Enhances tau's ability to aggregate and seeding potency. Reduces tau's ability to promote microtubule assembly and bind to microtubules, with increased binding of tubulin dimers. Reduces binding to protein phosphatase 2A. |
Bugiani et al., 1999; Sperfeld et al., 1999 |
| P301T |
FTD : Pathogenic, CBS : Pathogenic, GGT : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 10 | Globular deposits composed of four-repeat tau in astrocytes and oligodendrocytes, characteristic of globular glial tauopathy. Neuron loss in frontal cortex, substantia nigra, and spinal cord; spongiosis and astrogliosis in cortex and subcortical regions; neurofibrillary tangles; and demyelination of the corticospinal tracts. |
Unknown. |
Lladó et al., 2007; Erro et al., 2019 |
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