Mutations Position Table

MAPT P301 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
P301L
Frontotemporal Dementia Frontotemporal Dementia : Pathogenic

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 ╬▓-sheet formation and accelerates the formation of paired helical filament; Does not affect exon 10 splicing.

rs63751273
Coding
Exon 10
Point, Missense
CCG to CTG
8 Hutton et al., 1998;
Dumanchin et al., 1998;
Clark et al., 1998;
Spillantini et al., 1998
P301P
Frontotemporal Dementia Frontotemporal Dementia : Not Pathogenic

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.

rs63751395
Coding
Exon 10
Point, Silent
CCG to CCA
0 Miyamoto et al., 2001
P301S
Frontotemporal Dementia Frontotemporal Dementia : Pathogenic

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.

rs63751438
Coding
Exon 10
Point, Missense
CCG to TCG
3 Bugiani et al., 1999;
Sperfeld et al., 1999;
Lossos et al., 2003
P301T
Frontotemporal Dementia Frontotemporal Dementia : Pathogenic

Mild global atrophy that was more prominent in the frontal and temporal lobes.

Unknown.

rs63751438
Coding
Exon 10
Point, Missense
CCG to ACG
0 Llad├│ et al., 2007