FB2026_03 , released September 17, 2026
Human Disease Model Report: obesity and behavioral phenotypes (postulated), ETV5-related
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General Information
Name
obesity and behavioral phenotypes (postulated), ETV5-related
FlyBase ID
FBhh0000500
Disease Ontology Term
Parent Disease
OMIM
Overview

Several GWAS studies have implicated human ETV5 as a obesity susceptibility locus; in addition, ETV5-deficient mice have reduced body weight, lower fat mass, and are resistant to diet-induced obesity. ETV5 is one of multiple ETS ('E twenty-six') transcription factors in humans. In mammals, ETV5 mRNA is expressed in brain regions that are critical for the regulation of energy balance. There is a moderate-scoring orthologous gene in Drosophila, Ets96B, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\Ets96B is also orthologous to human genes ETV1 and ETV4. Pursuing the observation that obesity and bipolar disorder show some correlation (independent of medication) in humans, both metabolic and behavioral phenotypes have been assayed in flies with modified expression of Dmel\Ets96B.

The human ETV5 gene has not been introduced into flies. A UAS construct of the wild-type human Hsap\ETV1 gene has been introduced into flies, but has not been characterized.

RNAi-effected knockdown of Ets96B in the developing nervous system results in increased triacylglyceride concentration, a heightened startle-response, increased activity, and reduced sleep. Knockdown of Ets96B specifically in dopaminergic neurons recapitulates the subset of phenotypes tested. A small number of physical interactions have been described for Ets96B; see below and in the Ets96B gene report.

[updated Apr. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: obesity and behavioral phenotypes (postulated), ETV5-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Some of the symptoms of bipolar disorder and attention deficit hyperactivity disorder (ADHD) overlap. (http://www.healthline.com/health/bipolar-disorder/bipolar-or-adhd#1)

Genetics

ETV5 is associated with BMI or weight in multiple GWAS studies (see GWAS Catalog, below in 'External links').

Cellular phenotype and pathology
Molecular information

This gene encodes a member of the ETS (E twenty-six) family of transcription factors; all ETS proteins contain an ETS DNA-binding domain. The ETS proteins regulate many target genes that modulate biological processes like cell growth, angiogenesis, migration, proliferation and differentiation. (from NCBI Gene, ETV1, ETV5; 2017.02.21]

External links
Disease synonyms
obesity and behavorial phenotypes (postulated), ETV5-related
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one (3 human to 1 Drosophila); the 3 human genes are ETV1, ETV5, and ETV4; multiple lower-scoring orthologs exist in both species. The fly gene differs in N-terminal sequences.

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

    Many to one (3 human to 1 Drosophila); the 3 human genes are ETV1, ETV5, and ETV4; multiple lower-scoring orthologs exist in both species. The fly gene differs in N-terminal sequences.

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

    Many to one (3 human to 1 Drosophila); the 3 human genes are ETV1, ETV5, and ETV4; multiple lower-scoring orthologs exist in both species. The fly gene differs in N-terminal sequences.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate-scoring ortholog of human ETV1 and ETV5; lower-scoring ortholog of ETV4 (1 Drosophila to 3 human); Dmel\Ets96B shares 33-35% identity and 43-44% similarity with the human genes. The fly gene differs in N-terminal sequences.

      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 (2 groups)
        protein-protein
        Interacting group
        Assay
        References
        Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
        Models Based on Experimental Evidence ( 2 )
        Modifiers Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Interaction
        References
        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
        Related mammalian, viral, bacterial, or synthetic 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
        References (4)