FB2024_03 , released June 25, 2024
Allele: Dmel\Vps35UAS.R550W
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General Information
Symbol
Dmel\Vps35UAS.R550W
Species
D. melanogaster
Name
FlyBase ID
FBal0316904
Feature type
allele
Associated gene
Dmel\Vps35
Associated Insertion(s)
Carried in Construct
PBac{UAS-Vps35.R550W}
Key Links
Genomic Maps

Transgenic product class
missense_variant
(Malik et al., 2015)
Mutagen
Nature of the Allele
Transgenic product class
missense_variant
(Malik et al., 2015)
Mutagen
in vitro construct
(Malik et al., 2015)
Progenitor genotype
Carried in construct
PBac{UAS-Vps35.R550W}
Cytology
Description

UASt regulatory sequences drive expression of a mutated form of Vps35 that carries an amino acid substitution equivalent to R524W in the orthologous human VPS35 gene, a change whose pathogenicity is uncertain (the variant has been found both in sporadic patients with Parkinson's disease, but also in unaffected individuals). (FlyBase curator comment: the mutation in the Vps35 gene is given as R550W in FBrf0229809, however analysis of the release 6.32 annotated gene model indicates the change to be R551W).

(Malik et al., 2015)
Allele components
Component
Use(s)
Regulatory region(s)
UASt
Encoded product / tool
Vps35
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
point_mutation
2R:22,188,336..22,188,336 [+]
Nucleotide change:

A22188336T

Amino acid change:

R532W | Vps35-PA; R551W | Vps35-PB

Reported amino acid change:

R550W

Comment:

Analogous R524W mutation in human VPS35 implicated in Parkinson disease 17; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator based on reported amino acid change.

(Malik et al., 2015)
Variant Molecular Consequences
Associated Sequence Data
DDBJ / EMBL / GenBank
DNA sequence
Protein sequence
 
UniProtKB/Swiss-Prot
    UniProtKB/TrEMBL
      Expression Data
      Reporter Expression
      Additional Information
      Statement
      Reference
       
      Marker for
      Reflects expression of
      Reporter construct used in assay
      Human Disease Associations
      Disease Ontology (DO) Annotations
      Models Based on Experimental Evidence ( 1 )
      Disease
      Evidence
      References
      model of  Parkinson's disease
      CEA with Vps35MH20, Vps35E42
      (Malik et al., 2015)
      Modifiers Based on Experimental Evidence ( 1 )
      Disease
      Interaction
      References
      ameliorates  Parkinson's disease
      modeled by Vps35MH20, Vps35E42
      (Malik et al., 2015)
      Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
       

      Ubiquitous expression of Vps35Scer\UAS.R550W in wild type background does not result in dominant toxicity. Expression of Vps35Scer\UAS.R550W in a Vps35 mutant background largely rescues the phenotypes, but climbing defects are still observed.

      (Malik et al., 2015)
      Disease-implicated variant(s)
       
      This allele represents a human variant implicated in disease.
      (Malik et al., 2015)
      VPS35:p.Arg524Trp
      (FlyBase curators, 2019-)
      Variants Synonym(s)
      Associated human disease model(s)
      External database links
      ClinVar: VPS35_487673
      Comments concerning this variant
      Phenotypic Data
      Phenotypic Class
      Phenotype Manifest In
      Detailed Description
      Statement
      Reference

      Lifespan and motor ability are unaffected when Vps35Scer\UAS.R550W is expressed under the control of Scer\GAL4da.PU at 25[o]C. Lifespan is moderately shortened compared with controls at 29[o]C.

      No overt eye phenotypes are observed when Vps35Scer\UAS.R550W is expressed under the control of Scer\GAL4GMR.PU.

      Flies expressing Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU in a Vps35MH20/Vps35E42 mutant background show climbing defects.

      (Malik et al., 2015)
      External Data
      Interactions
      Show genetic interaction network for Enhancers & Suppressors
      Phenotypic Class
      Phenotype Manifest In
      Additional Comments
      Genetic Interactions
      Statement
      Reference

      Expression of Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU suppresses the climbing defects and increased sensitivity to paraquat seen in park25 mutants.

      (Malik et al., 2015)
      Xenogenetic Interactions
      Statement
      Reference
      Complementation and Rescue Data
      Partially rescues

      Scer\GAL4da.PU/Vps35UAS.R550W partially rescues Vps35MH20/Vps35E42

      (Malik et al., 2015)
      Comments

      Expression of Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU at 25[o] fails to rescue the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Vps35Scer\UAS.R550W at 29[o]C prevents the appearance of melanotic masses and fully rescues the developmental lethality, with progeny appearing in expected proportions.

      Expression of Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU at 29[o] rescues the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.

      Expression of Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU partially rescues the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.

      (Malik et al., 2015)
      Images (0)
      Mutant
      Wild-type
      Stocks (1)
      Notes on Origin
      Discoverer
      External Crossreferences and Linkouts ( 0 )
      Synonyms and Secondary IDs (2)
      Reported As
      Symbol Synonym
      Vps35Scer\UAS.R550W
      Vps35UAS.R550W
      Name Synonyms
      Secondary FlyBase IDs
        References (2)