|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
An αS '3K' mutant (E35K + E46K + E61K) that amplifies the PD/DLB-causing E46K mutation induced αS-rich vesicle clusters resembling the vesicle-rich areas of Lewy bodies, supporting pathogenic relevance.
|
28911198 |
2017 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Finally, we observed that the PD-linked mutation E46K enhances PLK2-mediated α-syn degradation, suggesting that this mutated form is a <i>bona fide</i> substrate of this degradation pathway.
|
28154193 |
2017 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Parkinson disease mutant E46K enhances α-synuclein phosphorylation in mammalian cell lines, in yeast, and in vivo.
|
25657004 |
2015 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Our findings add new insight into the preexisting information about α-synuclein p.E46K, improving our understanding about the endophenotypes associated to this mutation and corroborate that missense alterations and multiplications in α-synuclein are uncommon among Brazilian patients with Parkinson's disease.
|
25817515 |
2015 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Genetic studies have revealed that rare point mutations in the gene encoding α-synuclein including A30P, A53T, and E46K are associated with familial forms of PD, indicating a pathological role for mutant α-synuclein in PD etiology.
|
24833599 |
2014 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K) are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD.
|
23936403 |
2013 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.
|
23505409 |
2013 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
In this study, we created a BAC (bacterial artificial chromosome) transgenic rat model of PD expressing the E46K mutation of α-synuclein, which is pathogenic in humans.
|
23153578 |
2013 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
α-Synuclein (α-syn) is a synaptic protein in which four mutations (A53T, A30P, E46K and gene triplication) have been found to cause an autosomal dominant form of Parkinson's disease (PD).
|
22701661 |
2012 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Mutations in the gene for α-syn, including the E46K missense mutation, are sufficient to cause Parkinson disease as well as other synucleinopathies like dementia with LBs.
|
21846727 |
2011 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Three point mutants (A30P, A53T, and E46K) found in familial Parkinson disease also inhibited WPB exocytosis similar to that of wild-type alpha-synuclein.
|
20448034 |
2010 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Three familial variants of the presynaptic protein alpha-synuclein (alphaS), A30P, E46K, and A53T, correlate with rare inherited Parkinson's disease (PD), while wild-type alphaS is implicated in sporadic PD.
|
20041693 |
2010 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Among familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes alpha-synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates found in neurons in PD.
|
20106867 |
2010 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Altered ion channel formation by the Parkinson's-disease-linked E46K mutant of alpha-synuclein is corrected by GM3 but not by GM1 gangliosides.
|
20114052 |
2010 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Our results suggest that C-terminal-to-N-terminal contacts in alphaS are not strongly protective against aggregation, and that the dominant mechanism by which PD-linked mutations facilitate alphaS aggregation may be altering the physicochemical properties of the protein such as net charge (E46K) and secondary structure propensity (A30P and A53T).
|
19345692 |
2009 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Three missense mutations (A30P, A53T and E46K) in the alpha-syn gene are associated with rare autosomal dominant forms of familial PD.
|
18808659 |
2008 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
We investigated alpha-synuclein mutations, causative for autosomal dominant forms of Parkinson's disease (A30P, A53T and E46K), and phosphorylation mutants at serine 129 (S129A and S129D) using fluorescently labelled alpha-synuclein, actin and tau.
|
17408955 |
2007 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Three point mutations (A30P, E46K, and A53T) as well as gene triplication genetically link the 140-residue protein alpha-synuclein (aS) to the development of Parkinson disease.
|
16166095 |
2005 |
|
Parkinson Disease, Familial, Type 1
|
|
0.020 |
GeneticVariation
|
BEFREE |
The only alteration identified was the p.E46K mutation in a 60-year-old man, born in Bolivia, with a familial history of autosomal dominant Parkinson's disease.
|
25817515 |
2015 |
|
Parkinson Disease, Familial, Type 1
|
|
0.020 |
GeneticVariation
|
BEFREE |
Autosomal dominant Parkinson disease (PD) is caused by duplication or triplication of the alpha-synuclein gene as well as by the A30P, E46K, and A53T mutations.The mechanisms are unknown.
|
17012252 |
2006 |
|
Young onset Parkinson disease
|
|
0.010 |
GeneticVariation
|
BEFREE |
A30P and E46K are two mutants of α-synuclein (α-Syn) associated with familial early-onset Parkinson's disease (PD), and amyloid fibrils of α-Syn are the hallmarks of this disease.
|
30892349 |
2019 |
|
Small Fiber Neuropathy
|
|
0.010 |
GeneticVariation
|
BEFREE |
These results together with our previous findings support the relevance of E46K-SNCA mutation as a suitable model to study small fiber neuropathy in Lewy body diseases.
|
31178336 |
2019 |
|
Pure Autonomic Failure
|
|
0.010 |
GeneticVariation
|
BEFREE |
All E46K-SNCA carriers had moderate to severe p-synuclein deposits and small fiber neurodegeneration in different epidermal and dermal structures including nerve fascicles and glands, especially in carriers with Pure Autonomic Failure, while p-synuclein aggregates where absent in healthy controls and in one of two PARK2 carriers.
|
31178336 |
2019 |
|
Neurodegenerative Disorders
|
|
0.010 |
GeneticVariation
|
BEFREE |
Most aSyn mutations linked to neurodegenerative disease hindered neuronal survival in this model; of these mutations, the E46K mutation proved to be the most toxic.
|
28900007 |
2017 |
|
Familial (FPAH)
|
|
0.010 |
GeneticVariation
|
BEFREE |
Genetic studies have revealed that rare point mutations in the gene encoding α-synuclein including A30P, A53T, and E46K are associated with familial forms of PD, indicating a pathological role for mutant α-synuclein in PD etiology.
|
24833599 |
2014 |