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General Information
Name
alcohol, response to, ATG16L-related
FlyBase ID
FBhh0001118
OMIM
Overview

Drosophila mutants lacking the core autophagy gene Atg16 exhibit increased resistance to the sedative effects of ethanol; this phenotype is not observed for null mutants of other autophagy genes tested. Dmel\Atg16 is orthologous to two genes in human, ATG16L1 and ATG16L2; it is more closely related to ATG16L1. RNAi targeting constructs, alleles caused by insertional mutagenesis, and loss-of-function mutations caused by imprecise excision of TE insertions have been generated for Dmel\Atg16.

Neither human gene, ATG16L1 or ATG16L2, has been introduced into flies.

Dmel\Atg16 loss-of-function mutations exhibit defects in autophagy, resulting in related phenotypes, including reduced lifespan and neuromuscular dysfunction. Unexpectedly, Atg16 mutant animals are much more resistant to sedation upon exposure to ethanol than control flies. The Atg16 function in ethanol sensitivity maps to Corazonin-producing neurosecretory cells; Atg16 deficiency impairs production of the Corazonin (Crz) neuropeptide. (See human disease model report 'alcohol, response to, Crz neuropeptide-related' FBhh0001120).

[updated Oct. 2019 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, ATG16L-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

The protein encoded by ATG16L1 is part of a large protein complex that is necessary for autophagy (the major process by which intracellular components are targeted to lysosomes for degradation). Little is known about ATG16L2, which may have a similar function. [Gene Cards, ATG16L1 and ATG16L2; 2019.20.22]

External links
Disease synonyms
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.

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

    Many to one: 2 human to 1 Drosophila.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      Autophagy-related 16 (Atg16) encodes a protein that forms an E3-like protein complex. This complex contributes to the the covalent binding of the lipid phosphatidylethanolamine to the product of Atg8a, a key autophagy protein involved in autophagosome biogenesis. The product of Atg16 is involved in autophagosome biogenesis, maintenance of proper neuromuscular function, lifespan, ethanol sedation, and enteroendocrine cell function in the intestine. [Date last reviewed: 2019-03-21]
      Molecular function (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        High-scoring ortholog of ATG16L1; moderate-scoring ortholog of ATG16L2 (1 Drosophila to 2 human). Dmel\Atg16 shares 30-38% identity and 47-60% similarity with the 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 (6 groups)
          protein-protein
          Interacting group
          Assay
          References
          two hybrid, experimental knowledge based
          experimental knowledge based
          experimental knowledge based
          pull down, peptide massfingerprinting, two hybrid
          anti tag coimmunoprecipitation, anti tag western blot
          experimental knowledge based
          Alleles Reported to Model Human Disease (Disease Ontology) (5 alleles)
          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
          P-element activity
          amorphic allele - molecular evidence
          P-element activity
          References (5)