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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed November 2009

What is the official name of the ISCU gene?

The official name of this gene is “iron-sulfur cluster assembly enzyme.”

ISCU is the gene's official symbol. The ISCU gene is also known by other names, listed below.

What is the normal function of the ISCU gene?

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.

How are changes in the ISCU gene related to health conditions?

myopathy with deficiency of iron-sulfur cluster assembly enzyme - caused by mutations in the ISCU gene

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.

Where is the ISCU gene located?

Cytogenetic Location: 12q24.1

Molecular Location on chromosome 12: base pairs 108,561,463 to 108,569,384

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The ISCU gene is located on the long (q) arm of chromosome 12 at position 24.1.

The ISCU gene is located on the long (q) arm of chromosome 12 at position 24.1.

More precisely, the ISCU gene is located from base pair 108,561,463 to base pair 108,569,384 on chromosome 12.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about ISCU?

You and your healthcare professional may find the following resources about ISCU helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the ISCU gene or gene products?

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

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding ISCU?

amino acid ; cell ; cofactor ; deficiency ; DNA ; DNA repair ; domain ; E. coli ; enzyme ; gene ; glycine ; iron ; mitochondria ; muscle cells ; mutation ; protein ; skeletal muscle ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Kollberg G, Tulinius M, Melberg A, Darin N, Andersen O, Holmgren D, Oldfors A, Holme E. Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. Brain. 2009 Aug;132(Pt 8):2170-9. doi: 10.1093/brain/awp152. Epub 2009 Jun 30. (
  • Li K, Tong WH, Hughes RM, Rouault TA. Roles of the mammalian cytosolic cysteine desulfurase, ISCS, and scaffold protein, ISCU, in iron-sulfur cluster assembly. J Biol Chem. 2006 May 5;281(18):12344-51. Epub 2006 Mar 9. (
  • Mochel F, Knight MA, Tong WH, Hernandez D, Ayyad K, Taivassalo T, Andersen PM, Singleton A, Rouault TA, Fischbeck KH, Haller RG. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am J Hum Genet. 2008 Mar;82(3):652-60. doi: 10.1016/j.ajhg.2007.12.012. Epub 2008 Feb 14. (
  • NCBI Gene (
  • Olsson A, Lind L, Thornell LE, Holmberg M. Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. Hum Mol Genet. 2008 Jun 1;17(11):1666-72. doi: 10.1093/hmg/ddn057. Epub 2008 Feb 23. (
  • Rouault TA, Tong WH. Iron-sulfur cluster biogenesis and human disease. Trends Genet. 2008 Aug;24(8):398-407. doi: 10.1016/j.tig.2008.05.008. Epub 2008 Jul 5. Review. (
  • Tong WH, Rouault TA. Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell Metab. 2006 Mar;3(3):199-210. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: November 2009
Published: February 1, 2016