Variant "APP:c.2017G>A(p.Ala673Thr)"
Search results: 2 records
Variant information
Gene:
APP 
Variant:
APP:c.2017G>A(p.Ala673Thr) 
Genomic location:
chr21:27269932(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_000484.3:c.2017G>A(p.Ala673Thr)
protein_coding NM_001204301.1:c.1963G>A(p.Ala655Thr)
protein_coding NM_201413.2:c.1960G>A(p.Ala654Thr)
protein_coding NM_001136016.3:c.1945G>A(p.Ala649Thr)
protein_coding NM_001204302.1:c.1906G>A(p.Ala636Thr)
protein_coding NM_001136130.2:c.1849G>A(p.Ala617Thr)
protein_coding NM_201414.2:c.1792G>A(p.Ala598Thr)
protein_coding NM_001204303.1:c.1738G>A(p.Ala580Thr)
protein_coding NM_001136131.2:c.1687G>A(p.Ala563Thr)
protein_coding NM_001136129.2:c.1624G>A(p.Ala542Thr)
protein_coding NM_000484.3:c.2017G>A
protein_coding NM_001136016.3:c.1945G>A
protein_coding NM_001136129.2:c.1624G>A
protein_coding NM_001204301.1:c.1963G>A
protein_coding NM_001204302.1:c.1906G>A
protein_coding NM_001204303.1:c.1738G>A
show all
Alias:
APP:A673T 
dbSNP ID:
rs63750847  
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(1) ,Penetrance(1)  
Modifier effect:
Altered incidence(1) ,Risk factor and Altered onset time(1)  
Details：
  • Target disease:
    Alzheimer's Disease (DOID_10652)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor and Altered onset time 
    Evidence:
    Pedigree analysis 
    Effect:
    Reduced risk of Alzheimer disease or Early onset Alzheimer disease
    Alias in reference:
    APP:A673T
    Reference:
    PMID1671712
    Title:
    Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.
    Species studied:
    Human
    Abstract:
    A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.
  • Target disease:
    Alzheimer's Disease (DOID_10652)
    Effect type:
    Penetrance 
    Modifier effect:
    Altered incidence 
    Evidence:
    P=4.19×10(-5) 
    Effect:
    APP may protect against the disease
    Alias in reference:
    APP:c.2017G>A(p.Ala673Thr)
    Reference:
    PMID22801501
    Title:
    A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.
    Species studied:
    Human
    Abstract:
    The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.