The human gene ADGRL3 has been identified as a candidate susceptibility locus for attention deficit hyperactivity disorder (FBhh0000653). ADGRL3 encodes a G-protein-coupled receptor that functions in cell-cell adhesion and neuron guidance. There is a single orthologous gene in Drosophila, Dmel\Cirl, for which RNAi targeting constructs are available. Dmel\Cirl is also orthologous to multiple other adhesion G-protein-coupled receptor genes in human.
The human ADGRL3 gene has not been introduced into flies.
Pan-neuronal knockdown of Dmel\Cirl, effected by RNAi, results in hyperactivity and sleep loss; the phenotypes are more pronounced during night. Feeding with the ADHD-ameliorating pharmaceutical MPH (methylphenidate) results in reduction of the hyperactivity and sleep phenotypes.
[updated Nov. 2017 by FlyBase; FBrf0222196]
Attention-deficit/hyperactivity disorder (ADHD) is a chronic condition that includes a combination of persistent problems, such as difficulty sustaining attention, hyperactivity and impulsive behavior; the condition often continues into adulthood (https://www.mayoclinic.org/diseases-conditions/adhd/symptoms-causes/syc-20350889).
Meta-regression analyses have estimated the worldwide ADHD/HKD prevalence at between 5.3% and 7.1% in children and adolescents, and at 3.4% (range 1.2-7.3%) in adults (http://adhd-institute.com/burden-of-adhd/epidemiology/).
ADHD is the most common childhood-onset behavioral disorder, affecting approximately 5 to 10% of children and adolescents (Wolraich et al., 1996; pubmed: 8714320). In this condition, persistent inattention and/or hyperactive-impulsive behavior results in impaired social and/or academic functioning. Boys are affected about 8 times more frequently than girls (Zametkin et al., 1990; pubmed:2233902). [from MIM:143465; 2017.11.21]
ADHDgene (http://adhd.psych.ac.cn/) reports a number of studies that have assessed association of ADHD with natural variants of the ADGRL3 gene (under its previous symbol, LPHN3) [caveat emptor: the ADHDgene database has not been updated since Feb. 2014].
Adhesion G Protein-Coupled Receptor L3 (ADGRL3) encodes a member of the latrophilin subfamily of G-protein coupled receptors; it functions in cell-cell adhesion, neuron guidance, and development of glutamatergic synapses in the cortex. [Gene Cards, ADGRL3; 2017.11.21]
Many to one: 3 human to 1 Drosophila; multiple less closely related genes exist in both species. The human genes are ADGRL3, ADGRL1, ADGRL2.
Moderate-scoring ortholog of human ADGRL3, ADGRL1, and ADGRL2 (1 Drosophila to 3 human); there are multiple less closely related genes in both species, however, Dmel\Cirl is the best reverse hit for over a dozen genes in human. Cirl shares 22-23% identity and 36% similarity with human ADGRL3, ADGRL1, and ADGRL2 genes.
