Open Close
General Information
Name
copper metabolism disorders, ATP7-related
FlyBase ID
FBhh0000438
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes Drosophila models of copper metabolism disorders, ATP7-related. The human genes ATP7A and ATPB encode transmembrane copper-transporting ATPases; both have been implicated in copper metabolism disorders. There is a single fly gene orthologous to the two human genes, Dmel\ATP7, for which classical hypomorphic alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.

Disruptions in copper homeostasis are implicated in a number of diseases associated with cognitive and motor deficits. Either excess amounts of or deficiencies of elemental copper result in cellular damage and disease. Menkes disease (OMIM:309400, FBhh0000076) and occipital horn syndrome (OMIM:304150, FBhh0000078), both associated with ATP7A, are copper deficiency disorders; Wilson disease (OMIM:277900, FBhh0000079), associated with ATP7B, results from toxicity due to excess copper. Mutations in ATP7A are also implicated in X-linked distal spinal muscular atrophy (OMIM:300489, FBhh0000077), however, serum copper concentrations are normal in individuals with this disease.

Multiple UAS constructs of the human Hsap\ATP7A gene have been introduced into flies, including wild-type and a variant implicated in disease. ATP7B has not been introduced into flies.

Variants analogous to those implicated in a number of the diseases associated with ATP7A or ATP7B have been characterized in flies. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G1036E in the fly ATP7 gene (corresponds to G1300E in the human ATP7A gene, this variant implicated in Menkes disease, allele designated ATP7MNK.EGFP); P1122S in the fly ATP7 gene (corresponds to P1386S in the human ATP7A gene, this variant implicated in SMAX3, allele designated ATP7DMN.EGFP); S536G in the fly ATP7 gene (corresponds to S833G in the human ATP7A gene, this variant implicated in occipital horn syndrome, allele designated ATP7OHS.EGFP); H778Q in the fly ATP7 gene (corresponds to H1069Q in the human ATP7B gene, this variant implicated in Wilson disease, allele designated ATP7WND.EGFP); K552R in the fly ATP7 gene (corresponds to K832R in the human ATP7B gene, this variant postulated to confer susceptibility to Alzheimer disease, allele designated ATP7ALZ.EGFP). Variant(s) implicated in human disease tested (as transgenic human gene, ATP7A): the M1311V variant has been introduced into flies, this variant was isolated from an individual diagnosed with ALS.

A loss-of-function allele of the fly ATP7 gene is lethal during early larval stage when homozygous or hemizygous. Pan-neuronal overexpression of wild-type (tagged) Dmel\ATP7 results in reduced viability at all stages and visible adult phenotypes. Effected by gut-specific expression of RNAi directed against Dmel\ATP7, reduced levels in the digestive tract result in a reduced copper content in the head and body of surviving adults; a majority of these flies exhibit impaired neurological development during metamorphosis and die before eclosion. Genetics interactions of Dmel\ATP7 have been described; see the ATP7 gene record.

[updated Feb. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: copper metabolism disorders, ATP7-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
copper metabolism disorder
copper transport disorder
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila; the second human gene is ATP7A.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila; the second human gene is ATP7B.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    ATP7 (ATP7) encodes a copper transmembrane transporter involved in cuticle pigmentation, copper homeostasis and larval development. [Date last reviewed: 2019-09-12]
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human genes ATP7A and ATP7B (1 Drosophila to 2 human). DmelATP7 shares 46-47% identity and 62% similarity with human genes.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (9 alleles)
      Models Based on Experimental Evidence ( 7 )
      Modifiers Based on Experimental Evidence ( 6 )
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      loss of function allele
      Delta2-3 transposase
      References (25)