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ISCA1 gene

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

ISCA1 gene

The ISCA1 gene provides instructions for a protein that assembles iron-sulfur clusters, which are vital for mitochondrial energy production and various cellular functions.

Normal Function

The ISCA1 gene provides instructions for making a protein that is involved in the process of assembling molecules called iron-sulfur (Fe-S) clusters and attaching these clusters to other proteins. Certain proteins require Fe-S clusters to function properly.

The ISCA1 protein attaches to a similar protein called ISCA2. This allows the Fe-S assembly process to proceed and allows Fe-S clusters to attach to proteins. The ISCA1 protein is found in cellular structures called mitochondria, which are the energy-producing centers of cells. In these structures, several proteins carry out a series of chemical steps called oxidative phosphorylation to convert the energy in food into a form that cells can use. Many of the proteins that play a role in this process require Fe-S clusters to function. Proteins that contain Fe-S clusters are involved in many functions in the body, including DNA repair and the regulation of gene activity.

Health Conditions Related to Genetic Changes

Multiple mitochondrial dysfunctions syndrome

Pathogenic variants in the ISCA1 gene cause multiple mitochondrial dysfunctions syndrome type 5. This condition is characterized by vision problems and muscle stiffness (spasticity). People with type 5 have additional health problems that are common to all forms of multiple mitochondrial dysfunctions syndrome, such as severe brain dysfunction (encephalopathy) and a loss of mental abilities and acquired skills (developmental regression). Affected individuals have a shortened life expectancy.

Pathogenic variants in the ISCA1 gene lead to changes in single protein building blocks (amino acids) in the ISCA1 protein. These changes reduce the amount of functional ISCA1 proteins in the mitochondria. Without normal ISCA1 proteins, Fe-S clusters are not attached to proteins, and this means that certain proteins cannot perform their normal functions. Ultimately, this reduces the amount of energy produced by mitochondria and impairs cellular functions, leading to the severe signs and symptoms seen in people with multiple mitochondrial dysfunctions syndrome type 5.

Other Names for This Gene

  • HBLD2
  • hIscA
  • hIscA1
  • ISA1

Genomic Location

The ISCA1 gene is found on chromosome 9.

Frequently Asked Questions

This condition is inherited in an autosomal recessive pattern, meaning both parents must carry one copy of a pathogenic variant in the ISCA1 gene. If both parents are carriers, there is a 25 percent chance with each pregnancy that the child will inherit two copies of the variant and develop the syndrome, a 50 percent chance the child will be a carrier, and a 25 percent chance the child will not inherit the variant. Carrier testing is available for at-risk parents to determine their genetic status.
Early signs often appear in infancy and may include poor feeding, failure to thrive, and hypotonia (low muscle tone) that can later progress to spasticity (stiffness). Parents may also notice developmental delays, such as difficulty achieving milestones like sitting or walking. Vision problems, such as optic atrophy or nystagmus, are characteristic and may be observed as the child grows. Seizures and significant developmental regression are also common indicators that warrant immediate medical evaluation.
Genetic testing for ISCA1 variants is typically performed after clinical symptoms appear, as the condition is not included in standard newborn screening panels in most regions. However, if a child presents with unexplained developmental delays, movement disorders, or vision loss, a clinician may order a mitochondrial gene panel or whole exome sequencing that includes ISCA1. In families with a known history of the condition, targeted testing can be performed prenatally or on newborns to confirm the diagnosis early.
Life expectancy is generally shortened for individuals with this syndrome, with many patients not surviving into adulthood. The severity of the condition varies, but the progressive nature of the brain dysfunction (encephalopathy) and loss of acquired skills often leads to significant complications. Supportive care, including management of seizures, nutrition, and respiratory issues, is crucial to maintaining quality of life and potentially extending survival, though specific outcomes depend on the severity of the specific genetic variant and the presence of other health issues.
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.