In experiments in mouse and rat, orthologs of UNC13A have emerged as having roles in alcohol use and response. UNC13A (Unc-13 Homolog A) encodes a member of the UNC13 family; genes in this family are involved in neurotransmitter release and synaptic vesicle maturation. There is a single orthologous gene in Drosophila, unc-13, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\unc-13 is also orthologous to UNC13B and UNC13C in human.
None of the human UNC13 genes has been introduced into flies. A tagged wild-type version of the rat ortholog of UNC13A, Rnor\Unc13a, has been introduced; pan-neuronal expression of Rnor\Unc13a is able to suppress the increase in ethanol self-administration observed for a Dmel\unc-13 loss-of-function mutation.
The more extreme loss-of-function mutations of Dmel\unc-13 are lethal as homozygotes; embryos exhibit with defects in neurophysiology and synaptic vesicles. Adults heterozygous for a loss-of-function mutation exhibit a significant increase in ethanol self-administration.
[updated Jan. 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]
UNC13A encodes a protein involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion; it is essential for synaptic vesicle maturation. [Gene Cards, UNC13A; 2018.01.18]
Many to one (3 human to 1 Drosophila). The other human genes are UNC13B and UNC13C.
Moderate-scoring ortholog of human UNC13A, UNC13B and UNC13C (1 Drosophila to 3 human). Dmel\unc-13 shares 50% identity and 64% similarity with the human UNC13A gene.
