Normal Function
The BOLA3 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 BOLA3 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 BOLA3 gene cause multiple mitochondrial dysfunctions syndrome type 2. This condition is characterized by breathing difficulty (respiratory distress) and a weakened heart muscle (cardiomyopathy). People with type 2 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 usually do not survive past early childhood.
Pathogenic variants in the BOLA3 gene lead to changes in single protein building blocks (amino acids) in the BOLA3 protein, disrupt how genetic information is pieced together to make a blueprint for producing the protein, or result in an abnormally short protein. Without normal BOLA3 proteins, Fe-S cluster are not created, and this means that certain proteins cannot perform their normal functions. Ultimately, this reduces the amount of energy produced by mitochondria, contributing to the severe signs and symptoms seen in people with multiple mitochondrial dysfunctions syndrome type 2.
More About This Health ConditionOther Names for This Gene
- bolA homolog 3
- bolA-like protein 3
- BOLA3_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bargagna B, Banci L, Camponeschi F. Understanding the Molecular Basis of the Multiple Mitochondrial Dysfunctions Syndrome 2: The Disease-Causing His96Arg Mutation of BOLA3. Int J Mol Sci. 2023 Jul 21;24(14):11734. doi: 10.3390/ijms241411734. Citation on PubMed
- Cameron JM, Janer A, Levandovskiy V, Mackay N, Rouault TA, Tong WH, Ogilvie I, Shoubridge EA, Robinson BH. Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. Am J Hum Genet. 2011 Oct 7;89(4):486-95. doi: 10.1016/j.ajhg.2011.08.011. Epub 2011 Sep 22. Citation on PubMed or Free article on PubMed Central
- Haack TB, Rolinski B, Haberberger B, Zimmermann F, Schum J, Strecker V, Graf E, Athing U, Hoppen T, Wittig I, Sperl W, Freisinger P, Mayr JA, Strom TM, Meitinger T, Prokisch H. Homozygous missense mutation in BOLA3 causes multiple mitochondrial dysfunctions syndrome in two siblings. J Inherit Metab Dis. 2013 Jan;36(1):55-62. doi: 10.1007/s10545-012-9489-7. Epub 2012 May 5. Citation on PubMed
- Mayr JA, Feichtinger RG, Tort F, Ribes A, Sperl W. Lipoic acid biosynthesis defects. J Inherit Metab Dis. 2014 Jul;37(4):553-63. doi: 10.1007/s10545-014-9705-8. Epub 2014 Apr 29. Citation on PubMed
- Rouault TA. Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease. Dis Model Mech. 2012 Mar;5(2):155-64. doi: 10.1242/dmm.009019. Citation on PubMed or Free article on PubMed Central
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