FlyBase Allele Report: Dmel\mtDNA-helicase[A442P.UAS]

General Information

Symbol

Dmel\mtDNA-helicase^A442P.UAS

Species

D. melanogaster

Name

FlyBase ID

FBal0279448

Feature type

allele

Associated gene

Dmel\mtDNA-helicase

Associated Insertion(s)

Carried in Construct

P{UAS-mtDNA-helicase.A442P}

Key Links

Genomic Maps

JBrowse

Transgenic product class

missense_variant

(Sanchez-Martinez et al., 2012)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Sanchez-Martinez et al., 2012)

Mutagen

in vitro construct

(Sanchez-Martinez et al., 2012)

Progenitor genotype

Carried in construct

P{UAS-mtDNA-helicase.A442P}

Cytology

Description

UAS regulatory sequences drive expression of a mutated form of mtDNA-helicase which contains the amino acid replacement A442P.

(Sanchez-Martinez et al., 2012)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

mtDNA-helicase

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

2L:9,891,869..9,891,869 [-]

Nucleotide change:

G9891869C

Amino acid change:

A442P | mtDNA-helicase-PA

Reported amino acid change:

A442P

Comment:

Analogous A475P mutation in human TWNK implicated in Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator based on reported amino acid change.

(Sanchez-Martinez et al., 2012)

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 autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3

CEC

(Rodrigues et al., 2018)

model of autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 5

CEA

(Sanchez-Martinez et al., 2012)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3

is NOT ameliorated by Cint\AOX^UAS.cFa

(Rodrigues et al., 2018)

is NOT ameliorated by Cint\AOX^wt.UAS

(Rodrigues et al., 2018)

Comments on Models/Modifiers Based on Experimental Evidence ( 1 )

FlyBase curator comment: "autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3" is associated with human ortholog TWNK.

(Rodrigues et al., 2018)

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Sanchez-Martinez et al., 2012)

TWNK:p.Ala475Pro

(FlyBase curators, 2019-)

Variants Synonym(s)

TWNK:p.Ala21Pro

Associated human disease model(s)

progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 3

External database links

ClinVar: TWNK_4617

Comments concerning this variant

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

Detailed Description

Statement

Reference

Expressing mtDNA-helicase^A442P.UAS under the control of Scer\GAL4^da.PU leads to near full larval lethality, with very few individuals progressing through the pupal stage and until adulthood.

(Rodrigues et al., 2018)

Expression of mtDNA-helicase^{A442P.Scer\UAS} under the control of Scer\GAL4^da.G32 results in a significant decrease in mtDNA copy number in third instar larvae.

Wing discs of third instar larvae expressing mtDNA-helicase^{K388A.Scer\UAS} under the control of Scer\GAL4^da.G32 show an increase in apoptosis and a decrease in cell proliferation compare to wild type.

(Sanchez-Martinez et al., 2012)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Scer\GAL4^da.PU, mtDNA-helicase^A442P.UAS has increased mortality during development phenotype, enhanceable by Cint\AOX^mut.UAS, Scer\GAL4^da.PU

(Rodrigues et al., 2018)

Scer\GAL4^da.PU, mtDNA-helicase^A442P.UAS has increased mortality during development phenotype, enhanceable by Cint\AOX^wt.UAS, Scer\GAL4^da.PU