PSEN1 E120D (A>C)


Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73640295 A>C
dbSNP ID: rs63751272
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GAA to GAC
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 5


This mutation was described in a British kindred, known as family V. The reported pedigree had 10 affected individuals over four generations, four of whom were known to have autopsy-confirmed AD. The average age of onset in this family was 46, and ranged from 41 to 53 years. The mutation was detected in the four affected members of the family and in one at-risk individual under that age of 50 (Poorkaj et al., 1998).

This mutation was also detected in a French pedigree, known as ALZ 57, with four affected individuals over three generations. In this family onset ranged from 42 to 53, but clinical details were not reported other than that the family had early onset AD (Campion et al., 1999).

In a paper attempting to identify patterns of pathology associated with various familial AD mutations, two brain specimens from patients carrying E120D mutations were analyzed, but it was not indicated whether these individuals carried the A>T or A>C transversion. Age of onset in these individuals was recorded as 34 and 53 years and age at death as 51 and 62 years, respectively. Language loss, seizures, and rigidity were noted as clinical features (Mann et al., 2001).



Biological Effect

An in vitro assay using purified proteins to test the ability of a the E120D mutant (nucleotide change unspecified) to cleave the APP-C99 substrate revealed decreased Aβ42, and particularly Aβ40, production resulting in a greater than 5-fold increase in the Aβ42/Aβ40 ratio (Sun et al., 2017).

Last Updated: 15 Sep 2019


No Available Comments

Make a Comment

To make a comment you must login or register.


Paper Citations

  1. . Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene. Hum Mutat. 1998;11(3):216-21. PubMed.
  2. . Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet. 1999 Sep;65(3):664-70. PubMed.
  3. . Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease. Am J Pathol. 2001 Jun;158(6):2165-75. PubMed.
  4. . Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485. Epub 2016 Dec 5 PubMed.

Further Reading


  1. . Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update. J Med Genet. 2005 Oct;42(10):793-5. Epub 2005 Jul 20 PubMed.

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene. Hum Mutat. 1998;11(3):216-21. PubMed.

Other mutations at this position


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.