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
N296del
(ΔN296)
Progressive Supranuclear Palsy Other Tauopathy : Pathogenic, Frontotemporal Dementia : Not 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 the ability of tau to promote microtubule assembly and increases aggregation of tau into filaments.

rs63751392
Coding
Exon 10
Deletion
ATA 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 4-repeat (4R) tau.

Position 296 falls within a region that regulates exon 10 splicing. This mutation increases the splicing of exon 10 and reduces the ability of tau to promote tubulin polymerization and microtubule assembly without affecting tau filament formation.

[MET1] g.123774A>C
[NT1] g.120953A>C
rs63750416
Coding
Exon 10
Point, Missense
AAT to CAT
0 Iseki 2001
N296N
Frontotemporal Dementia Frontotemporal Dementia : Pathogenic

Characterized by abundant neuronal and glial tau protein deposits.

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

[MET1] g.123776T>C
[NT1] g.120955T>C
rs63750912
Coding
Exon 4a
Point, Silent
AAT to AAC
0 Spillantini 2000;
Grover 2002