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Normal Function
The C19orf12 gene provides instructions for making a protein whose function is unknown. The protein is found in the membrane of cellular structures called mitochondria, which are the cell's energy-producing centers. Researchers suggest that the C19orf12 protein plays a role in the maintenance of fat (lipid) molecules, a process known as lipid homeostasis.
Health Conditions Related to Genetic Changes
Mitochondrial membrane protein-associated neurodegeneration
At least 28 mutations in the C19orf12 gene have been found to cause a condition known as mitochondrial membrane protein-associated neurodegeneration (MPAN), which is characterized by movement and neurological problems that gradually worsen. Affected individuals also have an abnormal accumulation of iron in certain regions of the brain. The gene mutations that cause this condition change single protein building blocks (amino acids) in the C19orf12 protein or lead to an abnormally short protein. These changes likely reduce or eliminate the function of the protein. One C19orf12 gene mutation, which deletes 11 DNA building blocks (nucleotides) from the gene, is found in people of Polish descent who have the condition. This genetic change leads to production of an abnormally short protein, which is quickly broken down. It is unclear how loss of C19orf12 protein function leads to the signs and symptoms of MPAN. Researchers are working to determine whether there is a link between problems with lipid homeostasis and brain iron accumulation or how these abnormalities might contribute to the features of this disorder.
C19orf12 gene mutations can cause a spectrum of related conditions with some but not all of the characteristic features of MPAN. For example, some affected individuals have movement problems such as muscle stiffness (spasticity) but not iron accumulation in the brain; these individuals are considered to have a condition called hereditary spastic paraplegia type 43.
More About This Health ConditionOther Names for This Gene
- NBIA3
- NBIA4
- protein C19orf12
- SPG43
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Deschauer M, Gaul C, Behrmann C, Prokisch H, Zierz S, Haack TB. C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis. J Neurol. 2012 Nov;259(11):2434-9. doi: 10.1007/s00415-012-6521-7. Epub 2012 May 15. Citation on PubMed
- Dogu O, Krebs CE, Kaleagasi H, Demirtas Z, Oksuz N, Walker RH, Paisan-Ruiz C. Rapid disease progression in adult-onset mitochondrial membrane protein-associated neurodegeneration. Clin Genet. 2013 Oct;84(4):350-5. doi: 10.1111/cge.12079. Epub 2013 Jan 21. Citation on PubMed
- Hartig MB, Iuso A, Haack T, Kmiec T, Jurkiewicz E, Heim K, Roeber S, Tarabin V, Dusi S, Krajewska-Walasek M, Jozwiak S, Hempel M, Winkelmann J, Elstner M, Oexle K, Klopstock T, Mueller-Felber W, Gasser T, Trenkwalder C, Tiranti V, Kretzschmar H, Schmitz G, Strom TM, Meitinger T, Prokisch H. Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am J Hum Genet. 2011 Oct 7;89(4):543-50. doi: 10.1016/j.ajhg.2011.09.007. Citation on PubMed or Free article on PubMed Central
- Kruer MC, Salih MA, Mooney C, Alzahrani J, Elmalik SA, Kabiraj MM, Khan AO, Paudel R, Houlden H, Azzedine H, Alkuraya F. C19orf12 mutation leads to a pallido-pyramidal syndrome. Gene. 2014 Mar 10;537(2):352-6. doi: 10.1016/j.gene.2013.11.039. Epub 2013 Dec 17. Citation on PubMed or Free article on PubMed Central
- Landoure G, Zhu PP, Lourenco CM, Johnson JO, Toro C, Bricceno KV, Rinaldi C, Meilleur KG, Sangare M, Diallo O, Pierson TM, Ishiura H, Tsuji S, Hein N, Fink JK, Stoll M, Nicholson G, Gonzalez MA, Speziani F, Durr A, Stevanin G, Biesecker LG; NIH Intramural Sequencing Center; Accardi J, Landis DM, Gahl WA, Traynor BJ, Marques W Jr, Zuchner S, Blackstone C, Fischbeck KH, Burnett BG. Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12. Hum Mutat. 2013 Oct;34(10):1357-60. doi: 10.1002/humu.22378. Epub 2013 Aug 12. Citation on PubMed or Free article on PubMed Central
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