Mutations Position Table

PSEN1 M139 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
M139I (G>A)
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Possible mislocalization of presenilin-1 protein; co-localization with tangles.

Increased Aβ42/Aβ total ratio.

rs63750522
Coding
Exon 5
Point, Missense
ATG to ATA
0 Boteva et al., 1996
M139I (G>C)
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Possible mislocalization of presenilin-1 protein; co-localization with tangles.

Increased Aβ42/Aβ total ratio.

rs63750522
Coding
Exon 5
Point, Missense
ATG to ATC
0 Kim et al., 2010
M139K
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown.

Unknown.

rs63751106
Coding
Exon 5
Point, Missense
ATG to AAG
0 Dumanchin et al., 1998
M139L
Alzheimer's Disease Alzheimer's Disease : Pathogenic

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.


Coding
Exon 5
Point, Missense
ATG to TTG
0 Qiu et al., 2019
M139T
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown.

Increased Aβ42/Aβ40 ratio and decreased Aβ38/Aβ42 ratio in in vitro assay using patient brain samples. Increased Aβ42/Aβ total ratio in transfected cells.

 

rs63751106
Coding
Exon 5
Point, Missense
ATG to ACG
0 Campion et al., 1995
M139V
Alzheimer's Disease, Atypical Dementia Alzheimer's Disease : Pathogenic

Neuropathology consistent with AD.

Increased Aβ42/Aβ40, Aβ42/Aβ38, Aβ43/Aβ40, and Aβ2-40:Aβ40; decreased Aβ38/Aβ40, Aβ38/Aβ42, Aβ40/Aβ43, and Aβ11-40:Aβ40. Decreases Aβ40 and Aβ38 levels, while increasing Aβ42 and Aβ43 levels. Mutant protein levels were variable in iPSC-derived neurons suggesting protein instability.

 

 

rs63751037
Coding
Exon 5
Point, Missense
ATG to GTG
0 , 1995

Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.