This report describes the disease attention deficit hyperactivity disorder, susceptibility to (postulated), FBXO25-related. The human gene implicated in this disease, FBXO25, encodes an F-box protein; F-box proteins function in phosphorylation-dependent ubiquitination. There is a single orthologous gene in Drosophila, CG11658, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. CG11658 is also orthologous to a second gene in human, FBXO32.
The human FBXO25 gene has not been introduced into flies. A UAS construct of the human Hsap\FBOX32 gene has been introduced into flies, but has not been characterized.
Expanding upon data in human linking increased copy number and variants of FBXO25 with heritable ADHD, pan-neuronal overexpression of CG11658 in flies was assessed. Adult flies from either of two overexpression lines exhibit significantly elevated locomotor activity and reduced sleep in the relative night period.
[updated Oct. 2020 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]
FBXO25 encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. [Gene Cards, FBXO25; 2020.08.03]
Many to one: 2 human genes to 1 Drosophila gene.
High-scoring ortholog of human FBXO25 and FBXO32 (1 Drosophila to 2 human). Dmel\CG11658 shares 24-27% identity and 43-45% similarity with the human genes.
