YARS1: Tyrosyl-tRNA Synthetase 1
A critical enzyme for protein translation and a key player in Charcot-Marie-Tooth disease and other genetic disorders.
Gene Information Card
| Symbol | YARS1 |
|---|---|
| Full Name | Tyrosyl-tRNA Synthetase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p35.1 |
| NCBI Gene ID | 8567 ncbi.nlm.nih.gov/gene/8567 |
| Ensembl ID | ENSG00000116898 |
| UniProt ID | P54577 |
| OMIM ID | 603623 |
| HGNC ID | 12846 |
| Aliases | YRS, TYRRS, CMTDIC, YARS |
Description
YARS1 encodes the cytoplasmic tyrosyl-tRNA synthetase, an enzyme that catalyzes the attachment of tyrosine to its cognate tRNA, a critical step in protein translation. Beyond its canonical role, YARS1 has non-canonical functions in angiogenesis and immune signaling. Mutations in YARS1 are associated with Charcot-Marie-Tooth disease type C (CMTDIC) and other neuropathies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease, dominant intermediate C (CMTDIC) | Missense mutations impair tRNA charging and cause protein misfolding, leading to peripheral neuropathy. | ClinVar, OMIM |
| Charcot-Marie-Tooth disease, axonal, type 2N (CMT2N) | Loss-of-function mutations reduce tyrosyl-tRNA synthetase activity, affecting neuronal protein synthesis. | ClinVar, OMIM |
| YARS1-related intellectual disability | De novo missense variants disrupt enzyme function and are linked to neurodevelopmental phenotypes. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 15.3 | Medium |
| Liver | 18.7 | Medium |
| Skeletal Muscle | 20.1 | High |
| Kidney | 14.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.5 | High expression |
| HeLa | 18.9 | Medium expression |
| SH-SY5Y | 15.3 | Medium expression |
| HepG2 | 20.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.794C>T (p.Pro265Leu) | Missense | Unknown | Dominant negative effect; associated with CMTDIC |
| c.499G>A (p.Gly167Arg) | Missense | Unknown | Reduced tRNA charging activity; linked to CMT2N |
| c.1123G>A (p.Glu375Lys) | Missense | Unknown | Impaired dimerization and enzyme function; CMTDIC |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish tyrosyl-tRNA charging activity, e.g., p.Gly167Arg, leading to CMT2N.
Gain of Function (GOF)
Not well documented for YARS1; most pathogenic mutations are loss-of-function or dominant negative.
Dominant Negative (DN)
Mutations such as p.Pro265Leu that interfere with wild-type enzyme function, causing CMTDIC.
View complete mutation data：
Gene Ontology (GO)
| • tyrosyl-tRNA aminoacylation | • tRNA aminoacylation for protein translation |
| • tyrosine-tRNA ligase activity | • ATP binding |
| • cytoplasm | • angiogenesis |
Pathways
• Aminoacyl-tRNA biosynthesis (KEGG: hsa00970)
• tRNA charging (Reactome: R-HSA-379716)
Protein Summary
YARS1 is a 528-amino acid cytoplasmic tyrosyl-tRNA synthetase that belongs to the class I aminoacyl-tRNA synthetase family. It forms a homodimer and catalyzes the two-step reaction of tyrosine activation and transfer to tRNA(Tyr). The protein also contains an ELR motif that mediates cytokine-like activity, linking it to angiogenesis and inflammation. Mutations in YARS1 primarily cause peripheral neuropathy by disrupting protein translation in neurons.
Related Services
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