SARS1 is a human gene whose product encodes seryl-tRNA synthetase 1 (SerRS), an enzyme essential for protein synthesis. This enzyme catalyzes the attachment of serine to its cognate tRNA, a critical step in translation. Aminoacyl-tRNA synthetases also have diverse extra-translational functions including RNA splicing, cell signaling, and immune regulation[1]. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
| Gene Symbol | SARS1 |
|---|---|
| Full Name | Seryl-tRNA Synthetase 1 |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | [10781](https://www.ncbi.nlm.nih.gov/gene/10781) |
| OMIM | [607745](https://www.omim.org/entry/607745) |
| Ensembl ID | [ENSG00000022771](https://ensembl.org/Homo_species/Gene/Summary?g=ENSG00000022771) |
| UniProt | [Q9NP78](https://www.uniprot.org/uniprotkb/Q9NP78/entry) |
| Associated Diseases | Charcot-Marie-Tooth disease type 2G, neurodevelopmental disorders, cardiomyopathy |
SARS1 encodes seryl-tRNA synthetase 1 (SerRS), which catalyzes serine incorporation into proteins during translation[1:1]. Pathogenic variants in SARS1 cause Charcot-Marie-Tooth disease type 2G (CMT2G), a peripheral neuropathy characterized by motor and sensory deficits. Biallelic variants cause neurodevelopmental disorders with associated features. SARS1 is one of several aminoacyl-tRNA synthetases (ARS) linked to neurological diseases, highlighting the importance of translational machinery in neuronal health[2].
SARS1 encodes seryl-tRNA synthetase (SerRS), a class I aminoacyl-tRNA synthetase[1:2]. The enzyme catalyzes the following reaction:
Serine + tRNA(Ser) + ATP → Seryl-tRNA(Ser) + AMP + PPi
This aminoacylation reaction is essential for translational fidelity and efficiency. SerRS performs this function in the cytoplasm and has additional isoforms for mitochondrial translation.
Human SerRS is a 514-amino acid protein (UniProt Q9NP78) composed of:
The enzyme requires zinc for structural stability and catalytic function[3].
Beyond protein synthesis, SerRS has several extra-translational functions[4]:
CMT2G is an autosomal dominant peripheral neuropathy caused by SARS1 variants[6]:
Biallelic pathogenic SARS1 variants cause neurodevelopmental disorders[@togin2019]:
SARS1 variants have been associated with cardiomyopathy[7]:
SARS1 is expressed ubiquitously across all tissues:
Zebrafish studies show that morpholino knockdown of sars leads to[8]:
Sissler M, et al. Human mitochondrial aminoacyl-tRNA synthetases in disease and development. Trends in Cell Biology. 2017. ↩︎ ↩︎ ↩︎ ↩︎
Antonellis A, et al. The role of aminoacyl-tRNA synthetases in neurological disease. Nature Reviews Neurology. 2019. ↩︎ ↩︎
Wang H, et al. Structural basis of SARS1 catalysis and disease mechanisms. Journal of Molecular Biology. 2021. ↩︎
Beyer K, et al. Aminoacyl-tRNA synthetases in neurodegeneration. WIREs RNA. 2019. ↩︎ ↩︎
Roggenkranz C, et al. Seryl-tRNA synthetase in immune function and autoimmunity. Journal of Immunology. 2015. ↩︎
Hebrand S, et al. Mutations in SARS1 cause Charcot-Marie-Tooth disease type 2G. Nature Genetics. 2011. ↩︎ ↩︎
Lin Y, et al. SARS1 variants in cardiomyopathy. Cardiovascular Research. 2020. ↩︎ ↩︎
Xie W, et al. SARS1 mutations disrupt neuronal development in zebrafish. Development. 2017. ↩︎ ↩︎
Morelli K, et al. Novel SARS1 mutations and phenotype spectrum. Brain. 2020. ↩︎
Kim S, et al. Therapeutic strategies for SARS1-related peripheral neuropathy. Brain. 2021. ↩︎
Yang X, et al. CRISPR correction of SARS1 mutation in mouse model. Nature Medicine. 2022. ↩︎