Several small-scale GWAS studies in humans have contributed suggestive evidence supporting RYR3 as a susceptibility locus for alcohol use disorder (AUD). In human, RYR3 encodes one of several ryanodine receptors, which are intracellular calcium ion release channels responsible for the release of Ca(2+) from intracellular stores following transduction of a variety of extracellular stimuli. There is a single orthologous gene in Drosophila, Dmel\RyR, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\RyR is also orthologous to human RYR1 and RYR2.
None of the human ryanodine receptor genes has been introduced into flies.
Animals homozygous for an amorphic allele of Dmel\RyR usually die during the embryonic or early larval stage; larvae exhibit feeding, locomotion, and heart defects. Heterozygous animals show increased resistance to several tested chemicals, including paraquat and halothane. Adult flies homozygous for partial loss-of-function insertional mutations of RyR exhibit reduced ethanol rapid tolerance with no effects on initial sensitivity. Physical and genetic interactions of Dmel\RyR have been described; see below and in the RyR gene report.
[updated Jul. 2018 by FlyBase; FBrf0222196]
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 MIM:103780; 2017.12.19]
Ryanodine receptors, such as RYR3, are intracellular calcium ion release channels responsible for the release of Ca(2+) from intracellular stores following transduction of many different extracellular stimuli. [from MIM:180903; 2018.07.10]
Many to one: 3 human to 1 Drosophila; the other human genes are RYR1 and RYR2.
High-scoring ortholog of human RYR1, RYR2, RYR3 (1 Drosophila to 3 human). Dmel\RyR shares 44-46% identity and 61-63% similarity with the human genes.
