The human gene NKX6-3 was identified in genome-wide association study (GWAS) of two large low-caloric diet intervention cohorts of obese participants. The human NKX6-3 gene has not been introduced into flies.
There is a single orthologous gene in Drosophila,HGTX, for which multiple RNAi targeting constructs, a hypomorphic allele, UAS overexpression constructs, a GAL4 driver, and several P-element insertion alleles have been generated. HGTX is a homeodomain transcription factor of the ANTP class.
Ubiquitous expression of RNAi targeting HGTX causes 95% pupal lethality, with escapers having a significant reduction in triglyceride levels. Activating the RNAi knockdown in adults for 6 days produces a similar reduction in triglyceride levels. In the inducible knockdown animals, there is no significant change to levels of glycogen, trehalose, or change in body weight or starvation response. Driving HGTX RNAi with a driver specific to oenocytes (cells that process lipids: Gutierrez et al. 2007, FBrf0192579) causes the same effect, whereas fat body, muscle, and brain-specific drivers have no effect. Ubiquitous overexpression of HGTX causes a mild reduction in triglyceride levels.
[updated Mar. 2020 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).
NKX6-3 is a homeodomain transcription factor that is expressed in the developing CNS and gastrointestinal tract, where it participates in regulating differentiation, cell cycle, and cell death (pubmed:16326147, pubmed:26314965). In Drosophila, HGTX is a homeodomain transcription factor of the NK-like subgroup of the ANTP class, and has both activation and repression domains (Bürglin and Affolter 2016, FBrf0232555; Syu et al. 2019, FBrf0207814).
Many human genes to one Drosophila gene. Human genes are NKX6-1, NKX6-2, and NKX6-3.
Moderately-scoring ortholog of NKX6-3. Other human paralogs that HGTX is orthologous to include NKX6-1 and NKX6-2.
