Based on genome-wide association studies (GWAS) studies, the human gene Nudix hydrolase 3 (NUDT3) is postulated to have a role in susceptibility to obesity. NUDT3 is one of multiple related phosphohydrolases in the Nudix hydrolase family in humans; some members of this family degrade potentially mutagenic, oxidised nucleotides while others control the levels of metabolic intermediates and signalling compounds. In Drosophila, the gene Aps is orthologous to 4 human Nudix hydrolases, NUDT3, NUDT4, NUDT10 and NUDT11. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Aps.
A UAS construct of a tagged human Hsap\NUDT3 gene has been introduced into flies, but has not been characterized in the context of this disease model.
Effects of reduced function of Aps have been assayed using RNAi targeting neural tissues. Pan-neuronal RNAi expression results in animals that are more susceptible to starvation and have elevated lipid levels. Circulating glucose and trehalose levels are reduced compared with controls both with and without starvation. RNAi driven in the neurosecretory insulin-producing cells (IPCs), results in a decrease in circulating trehalose levels, a significant decrease of all carbohydrate levels under starvation conditions, and a decreased ability to recruit lipids during starvation.
[updated Feb. 2019 by FlyBase; FBrf0222196]
NUDT3 is associated with body mass index and hip circumference in GWAS studies (see GWAS Catalog, below in 'External links').
NUDT3 is one of multiple related phosphohydrolases in the Nudix hydrolase family in humans. Some Nudix hydrolases have the ability to degrade potentially mutagenic, oxidised nucleotides while others control the levels of metabolic intermediates and signalling compounds. The proteins encoded by the NUDT3, 4, 10 and 11 genes hydrolyse both nucleotide and non-nucleotide substrates. (McLennan, 2006; pubmed:16378245).
Many to one (4 human to 1 Drosophila); human genes are NUDT3, NUDT4, NUDT10, NUDT11.
Many to one (4 human to 1 Drosophila); human genes are NUDT3, NUDT4, NUDT10, NUDT11.
Many to one (4 human to 1 Drosophila); human genes are NUDT3, NUDT4, NUDT10, NUDT11.
Many to one (4 human to 1 Drosophila); human genes are NUDT3, NUDT4, NUDT10, NUDT11.
High-scoring ortholog of human NUDT3, NUDT4, NUDT10, and NUDT11 (1 Drosophila to 4 human). Dmel\Aps shares 54-59% identity and 69-74% similarity with human genes.
