Mutations Position Table
PSEN1 M139 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| M139I (G>A) |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Possible mislocalization of presenilin-1 protein; co-localization with tangles. |
Increased Aβ42/Aβ total ratio. |
Boteva et al., 1996 |
| M139I (G>C) |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Possible mislocalization of presenilin-1 protein; co-localization with tangles. |
Increased Aβ42/Aβ total ratio. |
Kim et al., 2010 |
| M139K |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown. |
Unknown, but multiple in silico algorithms predicted a damaging effect. |
Dumanchin et al., 1998 |
| M139R |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown |
Unknown, but an in silico algorithm predicted it is damaging (PHRED-scaled CADD score >20). |
|
| M139T |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown. |
Increased Aβ42/Aβ40 ratio and decreased Aβ (37 + 38 + 40) / (42 + 43), Aβ37/Aβ42, and Aβ38/Aβ42 ratios in cells. |
Campion et al., 1995 |
| M139L |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Unknown, but MRI in two individuals revealed bilateral atrophy in the hippocampus and cerebral cortex. |
Aβ40 levels moderately decreased; Aβ42/Aβ40 ratio increased in cultured cells. |
Qiu et al., 2019; Gao et al., 2019 |
| M139V |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 5 | Neuropathology consistent with AD. |
Increased Aβ42/Aβ40, Aβ42/Aβ38, Aβ43/Aβ40, and Aβ2-40:Aβ40; decreased Aβ (37 + 38 + 40) / (42 + 43) and Aβ37/Aβ42, Aβ38/Aβ40, Aβ38/Aβ42, Aβ40/Aβ43, and Aβ11-40/Aβ40 ratios. Decreased Aβ40, Aβ38, and Aβ37 levels, while increasing Aβ42 and Aβ43. Mutant protein levels were variable in iPSC-derived neurons suggesting protein instability.
|
Alzheimer's Disease Collaborative Group, 1995 |
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