The human gene TRAPPC9 has been identified as a candidate susceptibility locus for attention deficit hyperactivity disorder. TRAPPC9 encodes a pro-NFκB signaling protein which is also associated with mental retardation, autosomal recessive 13 (MIM:611966). There is a single orthologous gene in Drosophila, Dmel\brun, for which alleles carrying RNAi targeting constructs and alleles caused by insertional mutagenesis and CRISPR have been generated.
The human gene TRAPPC9 has not been introduced into flies.
Pan-neuronal knockdown of brun shows no activity or sleep phenotypes. However, specific knockdown of brun in dopaminergic neurons causes reduced activity and increased sleep during the day. In contrast, knocking brun down in tim-expressing circadian neurons causes increased activity and reduced sleep at night, which are behaviors associated with fly models of ADHD (FBhh0000653).
[updated Jun. 2020 by FlyBase; FBrf0222196]
The role of circadian genes and circuits in ADHD has been implicated, as ADHD often goes together with sleep disturbances, and abnormal circadian rhythms of melatonin secretion have been observed in children and adult patients with ADHD. Notably, positive genetic correlations between insomnia and sleep-related traits and ADHD exist. Abnormal circadian rhythms of melatonin secretion have been observed in children and adult patients with ADHD. Notably, positive genetic correlations between insomnia and sleep-related traits and ADHD exist. (Adapted from Klein et al. 2020 and references therein, FBrf0245813.)
Trafficking protein particle complex 9 (TRAPPC9) is a protein subunit of the transport protein particle II (TRAPPII), which has been reported to be important in the trafficking of cargo from the endoplasmic reticulum (ER) to the Golgi, and in intra‑Golgi and endosome‑to‑Golgi transport in yeast cells. In mammalian cells, TRAPPII has been shown to be important in Golgi vesicle tethering and intra‑Golgi transport. TRAPPC9 is considered to be a novel molecule capable of modulating the activation of nuclear factor‑κB (NF‑κB). (Mbimba et al. 2018 and references therein, pubmed:30272317.)
One to one: 1 human gene to 1 Drosophila gene.
Single, high-ranking ortholog of human TRAPPC9.
