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RARS2
arginyl-tRNA synthetase 2, mitochondrial
The RARS2 gene provides instructions for mitochondrial arginyl-tRNA synthetase, an enzyme crucial for protein synthesis within the cell's energy-producing mitochondria. RARS2 encodes an enzyme responsible for attaching the amino acid arginine to its specific transfer RNA (tRNA) molecule in the mitochondria.
RARS2 is located on the long (q) arm of chromosome 6, at band 6q15. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The RARS2 gene is vital for the proper functioning of mitochondria, which are often referred to as the 'powerhouses' of the cell. It carries the genetic blueprint for an enzyme called mitochondrial arginyl-tRNA synthetase. This enzyme plays a critical role in protein synthesis within mitochondria, a process essential for generating energy from food.
Disruptions in the RARS2 gene can lead to a range of neurological conditions, notably pontocerebellar hypoplasia type 6 (PCH6). Understanding the function of RARS2 is important for comprehending the genetic basis of these mitochondrial disorders.
What the gene does
The RARS2 gene directs the production of mitochondrial arginyl-tRNA synthetase, an enzyme located within the mitochondria. This enzyme is crucial for mitochondrial protein synthesis, a process fundamental to cellular energy production. Specifically, mitochondrial arginyl-tRNA synthetase facilitates the attachment of the amino acid arginine to its corresponding transfer RNA (tRNA) molecule.
Transfer RNA molecules act as adaptors, recognising specific codons on messenger RNA (mRNA) and delivering the correct amino acid to the growing protein chain. By linking arginine to tRNA, the RARS2 enzyme ensures that arginine is incorporated accurately into new proteins being assembled inside the mitochondria. This precise aminoacylation step is vital for the synthesis of functional mitochondrial proteins, which are essential for various metabolic pathways.
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Chromosome location
The RARS2 gene is situated on chromosome 6, specifically at band 6q15. This location describes the precise position of the gene within the human genome. Chromosome 6 contains a large number of genes involved in diverse biological functions.
Protein structure
The RARS2 gene encodes a protein consisting of 578 amino acids. A notable structural feature of this protein is a 'HIGH' region, which spans amino acids 133-144. This motif is typically involved in the aminoacylation process, specifically in binding ATP and the amino acid substrate to facilitate the synthesis of aminoacyl-tRNA.
Key variants
Variants within the RARS2 gene can alter the function of the mitochondrial arginyl-tRNA synthetase enzyme. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions. Such alterations may impair the enzyme's ability to correctly attach arginine to its tRNA, thereby disrupting mitochondrial protein synthesis and impacting cellular energy production.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Variants in the RARS2 gene are associated with various inherited conditions, primarily affecting neurological development and function. These conditions often fall under the category of mitochondrial disorders. Pontocerebellar hypoplasia type 6 (PCH6) is a notable condition linked to RARS2 gene variants, characterised by brain development abnormalities, movement problems, and intellectual disability.
No disease links recorded for this gene in our reference set.
UK clinical status
The RARS2 gene is included on several panels within the NHS Genomic Medicine Service's PanelApp, indicating its relevance for diagnostic testing in the UK. These include panels for "Mitochondrial disorders", "Pontocerebellar hypoplasia", "Intellectual disability", "Ataxia and cerebellar anomalies - childhood onset", and "Hereditary ataxia, adult onset". It is also listed on the "Foetal anomalies" and "Likely inborn error of metabolism" panels, underscoring its broad clinical significance.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the RARS2 gene?
The RARS2 gene provides instructions for an enzyme called mitochondrial arginyl-tRNA synthetase. This enzyme is responsible for attaching the amino acid arginine to its specific transfer RNA (tRNA) molecule within the mitochondria, a crucial step for building proteins inside these cellular organelles.
What happens if the RARS2 gene does not function correctly?
If the RARS2 gene does not function correctly, it can disrupt mitochondrial protein synthesis, leading to various disorders. These are often neurological conditions, such as pontocerebellar hypoplasia type 6 (PCH6), which can cause developmental delays, movement difficulties, and intellectual disability.
Is RARS2 relevant for carrier screening?
RARS2 is associated with inherited conditions, and its variants can be identified through carrier screening, particularly in the context of mitochondrial or neurological disorders. Carrier screening helps individuals understand their reproductive risk for passing on certain genetic conditions to their children.
References
- Cassandrini D, Cilio MR, Bianchi M. Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients. Journal of inherited metabolic disease. 2013. PMID: 22569581
- Glamuzina E, Brown R, Hogarth K. Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2. Journal of inherited metabolic disease. 2012. PMID: 22086604
- Namavar Y, Barth PG, Kasher PR. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain : a journal of neurology. 2011. PMID: 20952379
- Edvardson S, Shaag A, Kolesnikova O. Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. American journal of human genetics. 2007. PMID: 17847012