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DARS1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

DARS1 gene

The DARS1 gene provides instructions for making an enzyme essential for protein synthesis, and mutations in this gene are linked to a specific neurological condition.

Normal Function

The DARS1 gene provides instructions for making an enzyme called aspartyl-tRNA synthetase. This enzyme is found in all cell types and plays an important role in the production (synthesis) of proteins. During protein synthesis, building blocks called amino acids are connected together in a specific order to create a chain. A type of RNA called transfer RNA (tRNA) carries a specific amino acid to the growing chain. Enzymes called aminoacyl-tRNA synthetases, including aspartyl-tRNA synthetase, attach a particular amino acid to a specific tRNA. Aspartyl-tRNA synthetase attaches the amino acid aspartate to the correct tRNA, which helps ensure that aspartate is added at the proper place in proteins. In addition to its role in protein synthesis, this enzyme may have other functions that are not fully understood.

Health Conditions Related to Genetic Changes

Hypomyelination with brainstem and spinal cord involvement and leg spasticity

At least 16 mutations in the DARS1 gene have been found to cause a condition called hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL). This condition is characterized by abnormalities of the nervous system's white matter, usually involving particular regions of the spinal cord and brainstem. The white matter consists of nerve fibers covered by a fatty substance called myelin, which insulates the fibers and promotes the rapid transmission of nerve impulses. In HBSL, the nervous system has a reduced ability to form myelin (hypomyelination). Affected individuals develop muscle stiffness (spasticity) in the legs that worsens over time and impairs walking.

Most of the mutations in the DARS1 gene change single amino acids in the aspartyl-tRNA synthetase enzyme. These alterations occur in a region of the enzyme called the active site, where aspartate and the tRNA come together. The altered enzyme has difficulty adding the amino acid to the tRNA, which hinders the addition of aspartate to proteins. It is currently unclear how these mutations lead to the specific signs and symptoms of HBSL or why reduced activity of this enzyme affects myelination in specific parts of the brainstem and spinal cord.

Other Names for This Gene

  • Asp tRNA Ligase
  • Aspartate tRNA Ligase
  • aspartate tRNA ligase 1, cytoplasmic
  • Aspartyl tRNA Synthetase
  • DARS
  • Synthetase, Aspartyl-tRNA

Frequently Asked Questions

Yes, HBSL is an inherited condition. It is caused by mutations in the DARS1 gene, which are typically passed down in an autosomal recessive pattern. This means an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. Parents who are carriers usually do not show symptoms themselves.
Individuals with HBSL typically develop muscle stiffness, known as spasticity, in their legs, which tends to worsen over time and can impair movement. This condition is also characterized by abnormalities in the brain's white matter, specifically reduced myelin formation, which affects nerve signal transmission.
Treatment for HBSL focuses on managing symptoms, particularly the leg spasticity. This may include physical therapy to maintain mobility and reduce stiffness, occupational therapy to assist with daily activities, and sometimes medications to help relax muscles. There is currently no cure for the underlying genetic cause.
Diagnosis of HBSL usually involves a combination of clinical evaluation for symptoms like leg spasticity, imaging studies such as an MRI to detect white matter abnormalities and hypomyelination in the brainstem and spinal cord, and genetic testing to identify specific mutations in the DARS1 gene.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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