The CISD2 gene provides instructions for making a protein that is found in the outer membrane of cell structures called mitochondria. Mitochondria are involved in a wide variety of cellular activities, including energy production, chemical signaling, and regulation of cell growth and division. The exact function of the CISD2 protein is unknown, but it is thought to help keep mitochondria functioning normally.
Health Conditions Related to Genetic Changes
At least one mutation in the CISD2 gene has been found to cause Wolfram syndrome. This condition is characterized by a lack of insulin leading to increased blood sugar (diabetes mellitus), a degeneration of nerves that carry information from the eyes to the brain (optic atrophy), and a number of other features involving the urinary tract, the brain, and hearing. People with this CISD2 gene mutation also experience gastrointestinal ulcers and excessive bleeding after injury.
The CISD2 gene mutation that causes Wolfram syndrome replaces the amino acid glutamic acid with the amino acid glutamine at position 37 in the CISD2 protein (written as Glu37Gln or E37Q). This mutation results in an abnormally small, nonfunctional CISD2 protein. As a result, the function of the mitochondria is impaired and they eventually break down. Since the mitochondria provide energy to cells, the loss of mitochondria leads to decreased energy for cells. Cells that do not have enough energy to function will eventually die. Cells with high energy demands, such as nerve cells in the brain, eyes, or gastrointestinal tract, are most susceptible to cell death due to reduced energy. The gradual loss of cells in various body systems likely causes the signs and symptoms of Wolfram syndrome. When Wolfram syndrome is caused by CISD2 gene mutations, it is sometimes referred to as Wolfram syndrome type 2.More About This Health Condition
Other Names for This Gene
- CDGSH iron-sulfur domain-containing protein 2
- endoplasmic reticulum intermembrane small protein
- nutrient-deprivation autophagy factor-1
- zinc finger, CDGSH-type domain 2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Amr S, Heisey C, Zhang M, Xia XJ, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007 Oct;81(4):673-83. Epub 2007 Aug 20. Citation on PubMed or Free article on PubMed Central
- Chen YF, Wu CY, Kirby R, Kao CH, Tsai TF. A role for the CISD2 gene in lifespan control and human disease. Ann N Y Acad Sci. 2010 Jul;1201:58-64. doi: 10.1111/j.1749-6632.2010.05619.x. Review. Citation on PubMed
- Kanki T, Klionsky DJ. Mitochondrial abnormalities drive cell death in Wolfram syndrome 2. Cell Res. 2009 Aug;19(8):922-3. doi: 10.1038/cr.2009.94. Citation on PubMed or Free article on PubMed Central