|
PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET
|
|
0.800 |
GeneticVariation
|
UNIPROT |
EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease.
|
23279440 |
2013 |
|
PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET
|
|
0.800 |
CausalMutation
|
CLINVAR |
|
|
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes.
|
29016861 |
2017 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Although the most dramatic L166P point mutation practically eliminates DJ-1 protein and function, the effects of other PD-linked mutations are subtler.
|
23241025 |
2013 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Parkinson's disease DJ-1 L166P alters rRNA biogenesis by exclusion of TTRAP from the nucleolus and sequestration into cytoplasmic aggregates via TRAF6.
|
22532838 |
2012 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
In total, our results provide evidence that direct proteasomal endoproteolytic cleavage of DJ-1 L166P is the mechanism of degradation contributing to the loss-of-function of the mutant protein, a property not shared by other DJ-1 missense mutants associated with PD.
|
22173095 |
2012 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Parkinson disease (PD)-associated genomic deletions and the destabilizing L166P point mutation lead to loss of the cytoprotective DJ-1 protein.
|
19293155 |
2009 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Here we have used solution state NMR and circular dichroism spectroscopies to evaluate the extent of structural perturbations associated with five different Parkinson's disease linked DJ-1mutations: L166P, E64D, M26I, A104T, and D149A.
|
18436956 |
2008 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Molecular basis for the structural instability of human DJ-1 induced by the L166P mutation associated with Parkinson's disease.
|
18707128 |
2008 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Molecular dynamics calculations suggest that: (i) the structure of DJ-1 wild type (WT) in aqueous solution, in both oxidized and reduced forms, is similar to the crystal structure of the reduced form; (ii) the Parkinson disease-causing M26I variant is structurally similar to the WT, consistent with the experimental evidence showing the protein is a dimer as WT; (iii) R98Q is structurally similar to the WT, consistent with the fact that this is a physiological variant; and (iv) the L166P monomer rapidly evolves toward a conformation significantly different from WT, suggesting a change in its ability to oligomerize.
|
17504761 |
2007 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Both homozygous (L166P, M26I, deletion) and heterozygous mutations (D149A, A104T) in the DJ-1 gene have been identified in Parkinson's disease (PD) patients.
|
15944198 |
2005 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study.
|
15966003 |
2005 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Our studies revealed that the Parkinson's disease-linked L166P mutation impaired the intrinsic folding propensity of DJ-1 protein, resulting in a spontaneously unfolded structure that was incapable of forming a homodimer with itself or a heterodimer with wild-type DJ-1.
|
14665635 |
2004 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Deletion and point (L166P) mutations of DJ-1 have recently been shown to be responsible for the onset of familial Parkinson's disease (PD, PARK7).
|
14749723 |
2004 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
These properties of the L166P mutation may contribute to the loss of normal DJ-1 function and are likely to be the underlying cause of early onset PD in affected members of the Italian kindred.
|
14713311 |
2003 |
|
Young onset Parkinson disease
|
|
0.030 |
GeneticVariation
|
BEFREE |
Mutant oncogene DJ1 L166P has been linked to a familial form of early-onset Parkinson's disease (PD).
|
22571429 |
2012 |
|
Young onset Parkinson disease
|
|
0.030 |
GeneticVariation
|
BEFREE |
By performing a yeast two-hybrid screening from a human fetal brain library, we identified TRAF and TNF receptor-associated protein (TTRAP), an ubiquitin-binding domain-containing protein, as a novel DJ-1 interactor, which was able to bind the PD-associated mutations M26I and L166P more strongly than wild type.
|
19023331 |
2009 |
|
Young onset Parkinson disease
|
|
0.030 |
GeneticVariation
|
BEFREE |
A mutation in the human DJ-1 gene causing substitution of proline for leucine at residue 166 (L166P) has been linked to early onset Parkinson's disease.
|
18707128 |
2008 |
|
Autosomal Recessive Parkinsonism
|
|
0.010 |
GeneticVariation
|
BEFREE |
DJ-1/PARK7, But Not Its L166P Mutant Linked to Autosomal Recessive Parkinsonism, Modulates the Transcriptional Activity of the Orphan Nuclear Receptor Nurr1 In Vitro and In Vivo.
|
26873851 |
2016 |
|
Central neuroblastoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
To further investigate whether pathogenic mutations might prevent the distribution of DJ-1 to mitochondria, we generated human neuroblastoma cells stably transfected with wild-type (WT) or mutant (M26I, L166P, A104T, D149A) DJ-1 and performed mitochondrial fractionation and confocal co-localization imaging studies.
|
15944198 |
2005 |
|
Neuroblastoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
To further investigate whether pathogenic mutations might prevent the distribution of DJ-1 to mitochondria, we generated human neuroblastoma cells stably transfected with wild-type (WT) or mutant (M26I, L166P, A104T, D149A) DJ-1 and performed mitochondrial fractionation and confocal co-localization imaging studies.
|
15944198 |
2005 |
|
Childhood Neuroblastoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
To further investigate whether pathogenic mutations might prevent the distribution of DJ-1 to mitochondria, we generated human neuroblastoma cells stably transfected with wild-type (WT) or mutant (M26I, L166P, A104T, D149A) DJ-1 and performed mitochondrial fractionation and confocal co-localization imaging studies.
|
15944198 |
2005 |