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Normal Function
The IBA57 gene provides instructions for making a protein that is involved in the formation and transport of molecules called iron-sulfur (Fe-S) clusters. Certain proteins require Fe-S clusters to function properly.
The IBA57 protein is found in cellular structures called mitochondria. Mitochondria 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
Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the IBA57 gene cause multiple mitochondrial dysfunctions syndrome type 3. This condition is characterized by vision problems, progressive muscle stiffness (spasticity), and paralysis of the arms and legs (quadriplegia). People with type 3 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 IBA57 gene cause cells to produce altered versions of IBA57 proteins that do not function properly or at all. Without normal IBA57 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 3.
More About This Health ConditionOther disorders
A pathogenic variant in the IBA57 gene has been found to cause autosomal recessive spastic paraplegia type 74 (SPG74). This condition is part of a group of genetic disorders known as hereditary spastic paraplegias, which are characterized by muscle stiffness (spasticity) and paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are caused by the breakdown of nerve cells that trigger muscle movement (motor neurons). The pathogenic variant in the IBA57 gene that causes SPG74 was initially identified in one large group of related people. This variant severely decreases the function of the IBA57 protein.
Other Names for This Gene
- C1ORF69
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Hedera P. Uncomplicated (Pure) Hereditary Spastic Paraplegia Overview. 2000 Aug 15 [updated 2025 Jun 5]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1509/ Citation on PubMed
- Jiang H, Xu C, Duan R, Liu Z, Ren X, Li J, Chen C, Wang H, Han T, Tian X, Duan X, Song M, Li T, Fang F. Phenotypic spectrum of iron-sulfur cluster assembly gene IBA57 mutations: c.286 T > C identified as a hotspot mutation in Chinese patients with a stable natural history. J Hum Genet. 2025 Jan;70(1):25-32. doi: 10.1038/s10038-024-01291-0. Epub 2024 Sep 3. Citation on PubMed
- Liu M, Zhang J, Zhang Z, Zhou L, Jiang Y, Wang J, Xiao J, Wu Y. Phenotypic spectrum of mutations in IBA57, a candidate gene for cavitating leukoencephalopathy. Clin Genet. 2018 Feb;93(2):235-241. doi: 10.1111/cge.13090. Epub 2017 Dec 3. Citation on PubMed
- Lossos A, Stumpfig C, Stevanin G, Gaussen M, Zimmerman BE, Mundwiller E, Asulin M, Chamma L, Sheffer R, Misk A, Dotan S, Gomori JM, Ponger P, Brice A, Lerer I, Meiner V, Lill R. Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology. 2015 Feb 17;84(7):659-67. doi: 10.1212/WNL.0000000000001270. Epub 2015 Jan 21. Citation on PubMed
- Zhan F, Liu X, Ni R, Liu T, Cao Y, Wu J, Tian W, Luan X, Cao L. Novel IBA57 mutations in two chinese patients and literature review of multiple mitochondrial dysfunction syndrome. Metab Brain Dis. 2022 Feb;37(2):311-317. doi: 10.1007/s11011-021-00856-8. Epub 2021 Oct 28. Citation on PubMed
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