The human gene FARS2, which encodes mitochondrial phenylalanyl-tRNA synthetase, is implicated in two human diseases: combined oxidative phosphorylation deficiency 14 (MIM:614946, see FBhh0001429) and spastic paraplegia 77 (MIM:617046, see FBhh0001430). This report describes work done in Drosophila using the fly ortholog of FARS2, PheRS-m. A small number of genetic reagents have been generated for Dmel\PheRS-m including RNAi-targeting constructs and an amorphic mutation generated by genome editing using the CRISPR/Cas9 system.
Multiple UAS constructs of Hsap\FARS2 have been introduced into flies, including wild-type and variants implicated in disease. Partial heterologous rescue (functional complementation) has been demonstrated. See the 'Disease-Implicated Variants' table below.
Animals homozygous for an amorphic mutation of Dmel\PheRS-m die during a prolonged larval stage. Pan-neuronal knockout of Dmel\PheRS-m, effected by RNAi, results in developmental delay and a high level of pupal lethality, with some animals surviving to adulthood. Adult survivors exhibit bang sensitivity, a seizure-like phenotype.
[updated Feb. 2022 by FlyBase; FBrf0222196]
The spectrum of FARS2 deficiency ranges from the infantile-onset phenotype, characterized by epileptic encephalopathy with lactic acidosis and poor prognosis (70% of affected individuals), to the later-onset phenotype, characterized by spastic paraplegia, less severe neurologic manifestations, and longer survival (30% of affected individuals). [Gene Reviews, FARS2 deficiency; 2022.01.31]
FARS2 encodes mitochondrial phenylalanyl-tRNA synthetase, a protein that transfers phenylalanine to its cognate tRNA in the process of mitochondrial translation. [Gene Cards, FARS2; 2022.01.31]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human FARS2 (1 Drosophila to 1 human).
