|
Lewy Body Disease
|
|
0.860 |
CausalMutation
|
CLINVAR |
|
|
|
|
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 |
|
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 |
E46K mutant α-synuclein is more degradation resistant and exhibits greater toxic effects than wild-type α-synuclein in Drosophila models of Parkinson's disease.
|
31242217 |
2019 |
|
PARKINSON DISEASE 1, AUTOSOMAL DOMINANT (disorder)
|
|
0.700 |
GeneticVariation
|
UNIPROT |
A novel α-synuclein missense mutation in Parkinson disease.
|
23427326 |
2013 |
|
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 |
|
PARKINSON DISEASE 1, AUTOSOMAL DOMINANT (disorder)
|
|
0.700 |
GeneticVariation
|
UNIPROT |
Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.
|
9462735 |
1998 |
|
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 |
|
PARKINSON DISEASE 1, AUTOSOMAL DOMINANT (disorder)
|
|
0.700 |
GeneticVariation
|
UNIPROT |
Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease.
|
23457019 |
2013 |
|
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 |
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 |
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 |
|
Lewy Body Disease
|
|
0.860 |
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 |
Considering the potential interest of the skin as a target for the development of biomarkers in Parkinson's Disease (PD), in this work we aimed to evaluate structural and functional integrity of small autonomic nerve fibers and phosphorylated alpha-synuclein (p-synuclein) deposition in the skin of E46K-SNCA carriers as compared to those observed in parkin gene mutation (PARK2) carriers and healthy controls.
|
31178336 |
2019 |
|
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 |
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 |
|
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 |
|
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 |
Here, we generated mice expressing the fPD E46K mutation plus 2 homologous E→K mutations in adjacent KTKEGV motifs.
|
30308173 |
2018 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Here, we used an αS tetramer-abrogating mouse model of PD (3K) that amplifies the familial E46K PD mutation to investigate the effects of female sex and brain-selective estrogen treatment on αS tetramerization and solubility, formation of vesicle-rich αS<sup>+</sup> aggregates, dopaminergic and cortical fiber integrity, and associated motor deficits.
|
31405930 |
2019 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
In summary, we successfully generated Guangxi Bama minipigs harboring three PD-casusing mutations (E46K, H50Q and G51D) in SCNA.
|
30127453 |
2018 |
|
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 1, AUTOSOMAL DOMINANT (disorder)
|
|
0.700 |
GeneticVariation
|
UNIPROT |
Molecular determinants of α-synuclein mutants' oligomerization and membrane interactions.
|
25561023 |
2015 |
|
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 |
|
PARKINSON DISEASE 1, AUTOSOMAL DOMINANT (disorder)
|
|
0.700 |
GeneticVariation
|
UNIPROT |
Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.
|
9197268 |
1997 |