In GWAS studies, the human THADA gene has been associated with cold adaptation and type 2 diabetes. It is also in the region of a strongly selected SNP in modern human genomes compared to the Neanderthal genome (Green et al., 2010; pubmed:20448178). There is a single orthologous gene in Drosophila, also designated THADA, for which amorphic alleles created by targeted recombination and RNAi targeting constructs have been generated. Recent experiments characterizing the Drosophila ortholog show that the fly protein localizes primarily to the ER and that it modulates, via calcium signaling, energy storage and thermogenesis balance (FBrf0235198).
A UAS construct of the wild-type human Hsap\THADA gene has been introduced into flies. Heterologous rescue (functional complementation) has been demonstrated: the obesity phenotype of adults homozygous for an amorphic Dmel\THADA allele is rescued by induced expression of the human gene.
Animals that homozygous for amorphic alleles of Dmel\THADA are obese, hyperphagic, have reduced energy production, and are sensitive to the cold. A single physical interaction for Dmel\THADA has been described; see below and in the THADA gene report.
[updated Dec. 2017 by FlyBase; FBrf0222196]
Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. Obesity is associated with increased risk of illness, disability, and death. (http://medical-dictionary.thefreedictionary.com/obesity).
The development of obesity is recognized as having both genetic and environmental components (https://www.sciencelearn.org.nz/resources/203-obesity-genetic-or-environmental).
THADA is associated with Type 2 diabetes in multiple GWAS studies (see GWAS Catalog, below in 'External links').
Recent experiments characterizing the Drosophila ortholog show that THADA localizes primarily to the ER and that it modulates, via calcium signaling, energy storage and thermogenesis balance (FBrf0235198).
One to one: 1 human to 1 Drosophila.
Moderate-scoring ortholog of human THADA (1 Drosophila to 1 human); Dmel\THADA shares 22% identity and 38% similarity with the human gene.
