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 and accelerates the formation of paired helical filament; Does not affect exon 10 splicing. |
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 | Frontotemporal atrophy and extensive inclusions of hyperphosphorylated tau in neurons and glia. |
Recombinant tau protein with the P301S mutation showed a greatly impaired ability to promote microtubule assembly. |
Bugiani et al., 1999; Sperfeld et al., 1999; Lossos et al., 2003 |
| 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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