Mutations Position Table
MAPT S305 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| S305S |
FTD : Pathogenic, Other Tauopathy : Pathogenic | Substitution | Splicing Alteration | Isoform Shift; Silent | Coding | Exon 10 | Variable, but associated with cell loss, ballooned neurons, and tau-positive astrocytes, but limited cortical atrophy. Silver-positive neurofibrillary tangles associated with PSP diagnosis but not with FTDP-17 diagnosis. |
This silent mutation increases the splicing in of exon 10 and results in overproduction of tau isoforms containing four repeats (4R). |
Stanford et al., 2000; Skoglund et al., 2008 |
| S305I |
Other Tauopathy : Unclear Pathogenicity | Substitution | Splicing Alteration | Isoform Shift; Missense | Coding | Exon 10 | Extensive neuronal loss in the medial temporal cortex, hippocampus, and amygdala. No classical neurofibrillary tangles, Pick bodies, or neuritic plaques. Diffuse cytoplasmic tau in neurons, coiled bodies in oligodendrocytes, and argyrophilic grains. The tau-positive structures were composed only of 4-repeat (4R) isoforms. |
Affects exon 10 splicing, causing an overproduction of 4-repeat (4R) tau isoforms. |
Kovacs et al., 2008 |
| S305N |
FTD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 10 | Numerous neurofibrillary tangles including some with an unusual, ring-shaped morphology around the nucleus, especially in the frontal, temporal, insular, and postcentral cortices, as well as in the dentate gyrus. Neurofibrillary tangles in neurons and glia. |
Stem-loop instability leading to alterations in the ratio of 3-repeat (3R) tau to 4-repeat (4R) tau. Reduced lysosomal degradation of tau. |
Iijima et al., 1999; Kobayashi et al., 2002 |
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