In a genomic study of variants associated with obesity in humans, rare variants associated with the gene CAPN8 were identified. CAPN8 encodes a calpain, one of a large family of Ca(2+)-regulated cysteine proteases. There are multiple orthologous genes in Drosophila; the gene Dmel\CalpA was assessed for phenotypes associated with susceptibility to obesity. Multiple genetic reagents have been generated for Dmel\CalpA including loss-of-function mutations, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and over-expression constructs.
Animals homozygous for loss-of-function mutations of Dmel\CalpA are viable; they exhibit neuroanatomy and locomotor defects. Ubiquitous knockdown of CalpA, effected by RNAi, results in a significant increase in triacylglyceride (TAG) level, measured as the ratio of TAG to protein.
[updated Dec. 2021 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).
Calpains are intracellular Ca(2+)-regulated cysteine proteases. [MIM:618777; 2021.12.140]
Many to many: multiple related genes in both species.
Moderate- to high-scoring ortholog of multiple calpain genes in human, including CAPN8; multiple related genes in both species.
