FARS2: Phenylalanyl-tRNA Synthetase 2, Mitochondrial
A nuclear gene encoding the mitochondrial phenylalanyl-tRNA synthetase, essential for mitochondrial protein synthesis and implicated in neurodegenerative disorders.
Gene Information Card
| Symbol | FARS2 |
|---|---|
| Full Name | Phenylalanyl-tRNA Synthetase 2, Mitochondrial |
| Gene Type | Protein coding |
| Chromosomal Location | 6p25.1 |
| NCBI Gene ID | 27067 ncbi.nlm.nih.gov/gene/27067 |
| Ensembl ID | ENSG00000145982 |
| UniProt ID | O95363 |
| OMIM ID | 611592 |
| HGNC ID | 21062 |
| Aliases | FARS1, FARSLA, HSPC320, mtPheRS |
Description
FARS2 encodes the mitochondrial phenylalanyl-tRNA synthetase (mtPheRS), an enzyme that catalyzes the attachment of phenylalanine to its cognate mitochondrial tRNA (tRNAPhe). This aminoacylation reaction is critical for mitochondrial translation and oxidative phosphorylation. Mutations in FARS2 cause a spectrum of mitochondrial disorders, including autosomal recessive spastic paraplegia type 77 (SPG77) and early-onset epileptic encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spastic paraplegia 77 (SPG77) | Loss-of-function mutations impair mitochondrial tRNAPhe charging, leading to defective mitochondrial protein synthesis and axonal degeneration. | PMID: 25193669, ClinVar |
| Combined oxidative phosphorylation deficiency 14 (COXPD14) | Biallelic missense variants reduce mtPheRS activity, causing mitochondrial respiratory chain complex deficiencies. | PMID: 22985903, OMIM #614946 |
| Early-onset epileptic encephalopathy | Severe FARS2 mutations disrupt mitochondrial translation in neurons, resulting in seizures and developmental delay. | PMID: 28130635, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 10.8 | Medium |
| Liver | 8.2 | Low |
| Skeletal Muscle | 7.9 | Low |
| Kidney | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression in embryonic kidney cells |
| SH-SY5Y | 14.1 | High expression in neuroblastoma cells |
| HeLa | 11.7 | Medium expression in cervical cancer cells |
| HepG2 | 9.4 | Medium expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.986C>T (p.Thr329Ile) | Missense | Rare | Reduced catalytic activity; associated with SPG77 |
| c.431G>A (p.Arg144Gln) | Missense | Rare | Impaired tRNA binding; linked to COXPD14 |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of translation initiation; severe encephalopathy |
| c.1082_1083del (p.Glu361Glyfs*12) | Frameshift | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most FARS2 disease-associated mutations are loss-of-function, reducing or abolishing mitochondrial phenylalanyl-tRNA synthetase activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FARS2.
Dominant Negative (DN)
No dominant-negative mutations have been described; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • phenylalanine-tRNA ligase activity (GO:0004826) | • mitochondrion (GO:0005739) |
| • tRNA aminoacylation for protein translation (GO:0006418) | • phenylalanyl-tRNA aminoacylation (GO:0006432) |
| • mitochondrial matrix (GO:0005759) |
Pathways
• Mitochondrial tRNA aminoacylation (REACTOME R-HSA-379716)
• Mitochondrial translation (REACTOME R-HSA-5368287)
• Aminoacyl-tRNA biosynthesis (KEGG hsa00970)
Protein Summary
The FARS2 protein (mtPheRS) is a homodimeric enzyme localized to the mitochondrial matrix. Each subunit contains a catalytic domain and an anticodon-binding domain. It specifically charges mitochondrial tRNAPhe with phenylalanine, a prerequisite for mitochondrial protein synthesis. Structural studies show that pathogenic mutations cluster near the active site or tRNA-binding interface, disrupting aminoacylation efficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| No Data | ||||
