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General Information
Name
alcohol, response to, RhoGAP-related
FlyBase ID
FBhh0000691
OMIM
Overview

This report describes characterization of the fly alcohol response using the Drosophila gene RhoGAP18B, which is a Rho GTPase activating protein. Although there are multiple members of this gene family in both flies and human, RhoGAP18B is not a moderate- or high-scoring ortholog of any of the human genes. Loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\RhoGAP18B.

In a genetic screen for insertion mutations the result in altered sensitivity to ethanol, an allele of RhoGAP18B showed resistance to ethanol-induced sedation. As in most organisms, in wild-type flies low ethanol doses induce increased activity, while high doses are sedating. Different isoforms of RhoGAP18B appear to regulate the stimulant vs. the sedating effects. Genetic and physical interactions for Dmel\RhoGAP18B have been described; see below and in the RhoGAP18B gene report.

[updated Jan. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: alcohol use disorder, susceptibility to (fly models overview)
Symptoms and phenotype

Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).

The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)

Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).

Alcoholism is a multifactorial, genetically influenced disorder. [from OMIM:103780; 2017.12.19]

Specific Disease Summary: alcohol, response to, RhoGAP-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

Rho GTPase activating proteins (RhoGAPs or ARHGAPs) bind to and stimulate the GTPase activity of Rho family small GTPases (Rho GTPase activating proteins (ARHGAP); https://www.genenames.org/cgi-bin/genefamilies/set/721).

RhoGAP domain-containing proteins usually function to catalyze the hydrolysis of GTP that is bound to RHO, RAC and/or CDC42, inactivating these regulators of the actin cytoskeleton (Peck et al., 2002; pubmed:12297274) and thus impacting signaling pathways modulated by cytoskeletal changes.

External links
    Disease synonyms
    AUD susceptibility, RhoGAP-related
    Search term: alcohol use disorder
    Ortholog Information
    Human gene(s) in FlyBase
      Other mammalian ortholog(s) used
        D. melanogaster Gene Information (1)
        Gene Snapshot
        Rho GTPase activating protein at 18B (RhoGAP18B) encodes a protein that can act as a GTPase activating protein for several Rho GTPase and is involved in the regulation of actin dynamics. [Date last reviewed: 2019-08-01]
        Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        Very low-scoring ortholog of some human Rho GTPase activating proteins (RhoGAPs); multiple members of this gene family in both flies and human.

        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 (10 groups)
          protein-protein
          Interacting group
          Assay
          References
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, Identification by mass spectrometry
          anti tag coimmunoprecipitation, Identification by mass spectrometry
          experimental knowledge based
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, Identification by mass spectrometry
          Alleles Reported to Model Human Disease (Disease Ontology) (5 alleles)
          Models Based on Experimental Evidence ( 5 )
          Modifiers Based on Experimental Evidence ( 1 )
          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
          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
          P-element activity
          P-element activity
          Delta2-3 transposase
          References (9)