Mutations Position Table
MAPT N296 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| N296N |
FTD : Pathogenic, PSP : Pathogenic | Substitution | Substitution | Silent | Coding | Exon 10 | 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. |
Increased inclusion of exon 10 in tau mRNA and thus increased the ratio of 4R/3R tau protein. |
Spillantini et al., 2000 |
| N296del |
Other Tauopathy : Pathogenic, PD : Not Classified | Deletion | Deletion | Deletion | Coding | Exon 10 | 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. |
Pastor et al., 2001 |
| N296D |
FTD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 10 | Unknown; imaging showed temporal atrophy. |
Unknown. |
Cohn-Hokke et al., 2014 |
| N296H |
FTD : Pathogenic | Substitution | Splicing Alteration | Isoform Shift; Missense | Coding | Exon 10 | Localized frontotemporal lobe atrophy; A proliferation of tau-positive astrocytes; An accumulation of phosphorylated tau in both neurons and glia; 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. |
Iseki et al., 2001 |
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