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FB2026_01
,
released March 12, 2026
This report describes spastic paraplegia 77 (SPG77); SPG77 exhibits autosomal recessive inheritance. The human gene implicated in this disease is FARS2, which encodes mitochondrial phenylalanyl-tRNA synthetase. There is a single orthologous gene in Drosophila, 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. A variant implicated in SPG77, FARS2:p.Asp142Tyr , has been assessed in the context of rescue of phenotypes of a null mutation of Dmel\PheRS-m. Pan-neuronal expression of the human gene carrying this variant results in partial rescue, allowing survival to the adult stage. Surviving adults exhibit locomotor defects; this phenotype is not observed in the case of rescue with the wild-type human gene.
FARS2 is also implicated in a more severe disease, combined oxidative phosphorylation deficiency 14; see FBhh0001429. See, also, the human disease model report 'developmental delay and seizure, FARS2-related' (FBhh0001428).
[updated Feb. 2022 by FlyBase; FBrf0222196]
The hereditary spastic paraplegias (SPG, HSP) are a large group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'). [from MIM:182600; 15.06.29]
[SPASTIC PARAPLEGIA 77, AUTOSOMAL RECESSIVE; SPG77](https://omim.org/entry/617046)
[PHENYLALANYL-tRNA SYNTHETASE 2, MITOCHONDRIAL; FARS2](https://omim.org/entry/611592)
Spastic paraplegia-77 (SPG77) is an autosomal recessive neurologic disorder characterized by early-childhood onset of spasticity affecting the lower limbs and resulting in gait difficulties. The disorder is progressive and may be associated with childhood seizures, developmental delay, and mitochondrial dysfunction (Yang et al., 2016, pubmed:26553276; Vernon et al., 2015, pubmed:25851414; Vantroys et al., 2017, pubmed:29126765). [from MIM:617046; 2022.01.31]
Autosomal recessive spastic paraplegia-77 (SPG77) is caused by homozygous or compound heterozygous mutation in the FARS2 gene. [from MIM:617046; 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).