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

ISCU gene

The ISCU gene provides instructions for an enzyme that acts as a scaffold for assembling iron-sulfur clusters, which are vital for energy production and DNA repair.

Normal Function

The ISCU gene provides instructions for making a protein called the iron-sulfur cluster assembly enzyme. As its name suggests, this enzyme is involved in the formation of clusters of iron and sulfur atoms (Fe-S clusters). Specifically, the enzyme acts as a platform, or scaffold, for the assembly of these clusters.

Fe-S clusters are critical for the function of many different proteins, including those needed for DNA repair and the regulation of iron levels. Proteins containing Fe-S clusters are also necessary for energy production within mitochondria, which are the cell structures that convert the energy from food into a form that cells can use.

Health Conditions Related to Genetic Changes

Myopathy with deficiency of iron-sulfur cluster assembly enzyme

At least two mutations in the ISCU gene have been found to cause myopathy with deficiency of iron-sulfur cluster assembly enzyme. The more common mutation, written as IVS5+382G>C, alters the way the gene's instructions are pieced together to produce the enzyme. Most affected individuals have this mutation in both copies of the ISCU gene in each cell. The other mutation, which has been identified in one family, replaces the amino acid glycine with the amino acid glutamate at position 50 in the enzyme (written as Gly50Glu or G50E). Affected individuals in this family have had the G50E mutation in one copy of the ISCU gene in each cell and the IVS5+382G>C mutation in the other copy of the gene. This combination of mutations causes a severe variant of the disorder characterized by progressive muscle weakness and wasting.

Mutations in the ISCU gene severely limit the amount of iron-sulfur cluster assembly enzyme that is made in cells. A shortage of this enzyme prevents the normal production of proteins that contain Fe-S clusters, which disrupts a variety of cellular activities. A reduction in the amount of iron-sulfur cluster assembly enzyme is particularly damaging to skeletal muscle cells. Within the mitochondria of these cells, a lack of this enzyme causes problems with energy production and an overload of iron. These defects lead to muscle weakness, pain, and the other features of myopathy with deficiency of iron-sulfur cluster assembly enzyme.

Other Names for This Gene

  • HML
  • hnifU
  • iron-sulfur cluster scaffold homolog (E. coli)
  • IscU
  • IscU iron-sulfur cluster scaffold homolog
  • ISCU_HUMAN
  • ISU2
  • MGC74517
  • NIFU
  • NifU-like N-terminal domain containing
  • NIFUN
  • nitrogen fixation cluster-like

Genomic Location

The ISCU gene is found on chromosome 12.

Frequently Asked Questions

The definitive diagnosis combines targeted genetic testing for known ISCU mutations (e.g., IVS5+382G>C, Gly50Glu) with a muscle biopsy showing reduced activity of iron‑sulfur cluster enzymes (e.g., succinate dehydrogenase) and occasional ragged‑red fibers. Genetic confirmation is preferred because it avoids invasive procedures, but a biopsy may be performed when the genetic result is inconclusive.
No curative therapy exists, but management focuses on symptom control. Regular, low‑intensity aerobic exercise can improve mitochondrial efficiency without triggering severe fatigue. A balanced diet rich in complex carbohydrates and adequate protein supports muscle metabolism. Some clinicians trial riboflavin or coenzyme Q10 supplements, though evidence is limited; any supplement should be discussed with a neurologist.
ISCU‑related myopathy follows an autosomal‑recessive pattern. Both parents are typically carriers of one pathogenic allele. Each pregnancy carries a 25 % chance of an affected child, a 50 % chance of a carrier, and a 25 % chance of being unaffected and not a carrier. Carrier testing of siblings is recommended if the family’s specific mutations are known.
Patients usually present in late childhood to early adulthood (around 10‑25 years) with exercise‑induced muscle weakness, fatigue, and cramping. Episodes often worsen after prolonged activity and improve with rest. Some individuals develop mild respiratory involvement or difficulty climbing stairs, but severe cardiac disease is uncommon.
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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