EARS2
Glutamyl-tRNA Synthetase 2, Mitochondrial
Gene Information Card
| Symbol | EARS2 |
|---|---|
| Full Name | Glutamyl-tRNA Synthetase 2, Mitochondrial |
| Gene Type | Protein coding |
| Chromosomal Location | 16p12.2 |
| NCBI Gene ID | 124454 ncbi.nlm.nih.gov/gene/124454 |
| Ensembl ID | ENSG00000131095 |
| UniProt ID | Q5JPH6 |
| OMIM ID | 612799 |
| HGNC ID | 29419 |
| Aliases | GLURS, KIAA1970, mtGluRS |
Description
EARS2 encodes the mitochondrial glutamyl-tRNA synthetase, an enzyme that catalyzes the attachment of glutamate to its cognate mitochondrial tRNA (tRNAGlu). This protein is essential for mitochondrial protein synthesis. Mutations in EARS2 cause a form of leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL), also known as combined oxidative phosphorylation deficiency 12.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Combined oxidative phosphorylation deficiency 12 (COXPD12) | Loss-of-function mutations impair mitochondrial glutamyl-tRNA charging, reducing mitochondrial translation and oxidative phosphorylation. | ClinVar, OMIM |
| Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) | Biallelic missense or nonsense mutations lead to defective mitochondrial protein synthesis, causing neurodegeneration. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 8.4 | Medium |
| Heart muscle | 6.2 | Medium |
| Brain cortex | 5.1 | Low |
| Skeletal muscle | 4.8 | Low |
| Kidney | 7.0 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 9.1 | Hepatocellular carcinoma cell line |
| K-562 | 6.5 | Chronic myelogenous leukemia |
| HeLa | 5.8 | Cervical adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1004G>A (p.Arg335Gln) | Missense | Rare | Reduced enzyme activity; associated with LTBL |
| c.1439T>C (p.Leu480Pro) | Missense | Rare | Impaired tRNA binding; COXPD12 |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations reduce or abolish glutamyl-tRNA synthetase activity, leading to mitochondrial translation defects.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • glutamate-tRNA ligase activity | • mitochondrial matrix |
| • mitochondrial translation | • ATP binding |
| • tRNA aminoacylation for protein translation |
Pathways
• Mitochondrial aminoacyl-tRNA biosynthesis
• Mitochondrial translation
Protein Summary
EARS2 encodes a 523-amino acid mitochondrial glutamyl-tRNA synthetase (mtGluRS) that belongs to the class I aminoacyl-tRNA synthetase family. The protein contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and an anticodon-binding domain. It specifically charges mitochondrial tRNAGlu with glutamate, a critical step for mitochondrial protein synthesis. Defects in this enzyme disrupt oxidative phosphorylation, particularly in tissues with high energy demand such as brain and muscle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EARS2 Knockout HEK293 Cell Line | EDJ-KQ8556 | Human | 124454 | Details Get a Quote |
| EARS2 Knockout A-549 Cell Line | EDJ-KQ34706 | Human | 124454 | Details Get a Quote |
| EARS2 Knockout HCT 116 Cell Line | EDJ-KQ34707 | Human | 124454 | Details Get a Quote |
| EARS2 Knockout HeLa Cell Line | EDJ-KQ34708 | Human | 124454 | Details Get a Quote |
