Mutations Position Table

MAPT P301 Mutations

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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 filaments. Does not affect exon 10 splicing.

[MET1] g.123790C>T
[NT1] g.120969C>T
rs63751273
Coding
Exon 10
Point, Missense
CCG to CTG
7 Hutton 1998;
Dumanchin 1998;
Clark 1998;
Spillantini 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.

[MET1] g.123791G>A
[NT1] g.120970G>A
rs63751395
Coding
Exon 10
Point, Silent
CCG to CCA
0 Miyamoto 2001
P301S
Frontotemporal Dementia Frontotemporal Dementia : Pathogenic

Extensive filamentous hyperphosphorylated tau protein 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 1999;
Sperfeld 1999;
Lossos 2003
P301T
Frontotemporal Dementia Frontotemporal Dementia : Pathogenic

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

Unknown.

[MET1] g.123789C>A
[NT1] g.120968C>A
rs63751438
Coding
Exon 10
Point, Missense
CCG to ACG
0 Llad├│ 2007