Mutations Position Table

MAPT N296 Mutations

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Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
N296D
Frontotemporal Dementia Frontotemporal Dementia : Pathogenic

Unknown; imaging showed temporal atrophy.

Unknown.


Coding
Exon 10
Point, Missense
AAT to GAT
0 Cohn-Hokke 2014
N296del
(ΔN296)
Progressive Supranuclear Palsy, Parkinson's Disease Other Tauopathy : Pathogenic

Atrophy of the right precentral gyrus and the brainstem, as well as neuron loss and gliosis in the substantia nigra, several brainstem nuclei, and diencephalon. Hyperphosphorylated tau and neurofibrillary tangles in neurons in many brain regions. Accumulated tau in astrocytes and oligodendrocytes.

The N296del mutation has little or no effect on exon 10 splicing, but substantially reduces tau's ability to promote microtubule assembly and increases its aggregation into filaments.

rs63751392
Coding
Exon 10
Deletion
AAT to ---
0 Pastor 2001
N296H
Frontotemporal Dementia Frontotemporal Dementia : Pathogenic

Localized frontotemporal lobe atrophy, a proliferation of tau-positive astrocytes, an accumulation of phosphorylated tau in both neurons and glia, and an accumulation of four-repeat (4R) tau.

This mutation increases the inclusion of exon 10 in tau mRNA and therefore increases the ratio of 4R/3R tau. It reduces tau's ability to promote tubulin polymerization and microtubule assembly. It has little to no effect on tau filament formation.

rs63750416
Coding
Exon 10
Point, Missense
AAT to CAT
0 Iseki 2001
N296N
Frontotemporal Dementia, Progressive Supranuclear Palsy Frontotemporal Dementia : Pathogenic, Progressive Supranuclear Palsy : Pathogenic

Frontotemporal atrophy. Neuronal loss in the globus pallidus, substantia nigra, and locus ceruleus. Swollen achromatic neurons and tau-positive inclusions throughout the brain. Plaques and tangles were rare in the hippocampus and cerebral cortex.

This silent mutation increases the inclusion of exon 10 in tau mRNA and therefore increases the ratio of 4R/3R tau protein.

rs63750912
Coding
Exon 10
Point, Silent
AAT to AAC
0 Spillantini 2000