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General Information
Name
Alzheimer disease, susceptibility to (postulated), TM2D3-related
FlyBase ID
FBhh0000681
Disease Ontology Term
Parent Disease
OMIM
Overview

Initially identified in an exome-wide association analysis for late-onset Alzheimer disease, the human gene TM2D3 is proposed as a candidate susceptibility locus for Alzheimer disease. A member of the seven transmembrane domain G protein-coupled receptor superfamily, TM2D3 encodes a protein with sequence and structural similarities to the beta-amyloid binding protein, but it does not regulate a response to beta-amyloid peptide. There is a single orthologous gene in Drosophila, amx, for which a classical amorphic mutation, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The wild-type human Hsap\TM2D3 gene has been introduced into flies using constructs with the promoter and regulatory region of the fly amx gene; the human gene with a mutation implicated in late onset Alzheimer cloned into the same context has also been introduced. Variant(s) implicated in human disease tested (as transgenic human gene, TM2D3): the P155L variant form of the human gene has been introduced into flies. Partial heterologous rescue (functional complementation) of the maternal-effect lethal phenotype of Dmel\amx has been demonstrated. The P155L variant form of the human gene fails to rescue.

Mutations in Dmel\amx cause a strong maternal-effect neurogenic phenotype: females homozygous for an amorphic allele of amx are sterile; their offspring exhibit variable neurogenic phenotypes and die in the embryonic stage. A small number of genetic interactions have been described for Dmel\amx; see the amx gene report.

[updated Dec. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: Alzheimer disease, susceptibility to (postulated), TM2D3-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
The protein encoded by the TM2D3 (TM2 Domain Containing 3) gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. The TM2D3 protein has sequence and structural similarities to the beta-amyloid binding protein, but it does not regulate a response to beta-amyloid peptide. [from Gene Cards, TM2D3; 2017.12.05]
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)
One to one: 1 human to 1 Drosophila.
Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    In progress.Contributions welcome.
    Molecular function (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)
      Moderate-scoring ortholog of human TM2D3 (1 Drosophila to 1 human); Dmel\amx shares 51% identity and 64% similarity with the human gene.
      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 2 )
      Allele
      Disease
      Interaction
      References
      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
      amorphic allele - molecular evidence
      CRISPR/Cas9
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      References (5)