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Normal Function
The PANK2 gene provides instructions for making an enzyme called pantothenate kinase 2. This enzyme is active in specialized cellular structures called mitochondria, which are the cell's energy-producing centers. Within mitochondria, pantothenate kinase 2 regulates the formation of a molecule called coenzyme A. Coenzyme A is found in all living cells, where it is essential for the body's production of energy from carbohydrates, fats, and some protein building blocks (amino acids).
PANK2 is one of four human genes that provide instructions for making versions of pantothenate kinase. The functions of these different versions probably vary among tissue types and parts of the cell. The version produced by the PANK2 gene is active in cells throughout the body, including nerve cells in the brain.
Health Conditions Related to Genetic Changes
Pantothenate kinase-associated neurodegeneration
About 100 mutations in the PANK2 gene have been identified in people with pantothenate kinase-associated neurodegeneration. Typically, people with the more severe, early-onset form of the disorder have PANK2 mutations that prevent cells from producing any functional pantothenate kinase 2. People affected by the atypical, later-onset form usually have mutations that change single amino acids in the enzyme, which makes the enzyme unstable or disrupts its activity. In some cases, single amino acid changes allow the enzyme to retain some function. The most common PANK2 mutation replaces the amino acid glycine with the amino acid arginine at position 411 of the enzyme (written as Gly411Arg or G411R).
When pantothenate kinase 2 is altered or missing, the normal production of coenzyme A is disrupted and potentially harmful compounds can build up in the brain. This buildup leads to swelling, tissue damage, and an abnormal accumulation of iron in certain areas of the brain. Researchers are uncertain how a lack of functional pantothenate kinase 2 causes the specific features of pantothenate kinase-associated neurodegeneration. Because the enzyme functions in mitochondria, the signs and symptoms of this condition may be related to impaired energy production.
Mutations in the PANK2 gene are also found in people with a condition called HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration). HARP was historically described as a separate syndrome but is now considered part of pantothenate kinase-associated neurodegeneration. Although HARP is much rarer than classic pantothenate kinase-associated neurodegeneration, both conditions involve problems with movement, dementia, and vision abnormalities.
More About This Health ConditionOther Names for This Gene
- NBIA1
- PANK2_HUMAN
- pantothenate kinase 2 (Hallervorden-Spatz syndrome)
- pantothenic acid kinase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Gordon N. Pantothenate kinase-associated neurodegeneration (Hallervorden-Spatz syndrome). Eur J Paediatr Neurol. 2002;6(5):243-7. doi: 10.1053/ejpn.2002.0606. Citation on PubMed
- Gregory A, Hayflick SJ. Neurodegeneration with brain iron accumulation. Folia Neuropathol. 2005;43(4):286-96. Citation on PubMed or Free article on PubMed Central
- Hartig MB, Hortnagel K, Garavaglia B, Zorzi G, Kmiec T, Klopstock T, Rostasy K, Svetel M, Kostic VS, Schuelke M, Botz E, Weindl A, Novakovic I, Nardocci N, Prokisch H, Meitinger T. Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. Ann Neurol. 2006 Feb;59(2):248-56. doi: 10.1002/ana.20771. Citation on PubMed
- Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH, Gitschier J. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med. 2003 Jan 2;348(1):33-40. doi: 10.1056/NEJMoa020817. Citation on PubMed
- Hayflick SJ. Pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome). J Neurol Sci. 2003 Mar 15;207(1-2):106-7. doi: 10.1016/s0022-510x(02)00433-1. No abstract available. Citation on PubMed
- Hayflick SJ. Unraveling the Hallervorden-Spatz syndrome: pantothenate kinase-associated neurodegeneration is the name. Curr Opin Pediatr. 2003 Dec;15(6):572-7. doi: 10.1097/00008480-200312000-00005. Citation on PubMed
- Johnson MA, Kuo YM, Westaway SK, Parker SM, Ching KH, Gitschier J, Hayflick SJ. Mitochondrial localization of human PANK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration. Ann N Y Acad Sci. 2004 Mar;1012:282-98. doi: 10.1196/annals.1306.023. Citation on PubMed
- Kotzbauer PT, Truax AC, Trojanowski JQ, Lee VM. Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2. J Neurosci. 2005 Jan 19;25(3):689-98. doi: 10.1523/JNEUROSCI.4265-04.2005. Citation on PubMed
- Ponka P. Hereditary causes of disturbed iron homeostasis in the central nervous system. Ann N Y Acad Sci. 2004 Mar;1012:267-81. doi: 10.1196/annals.1306.022. Citation on PubMed
- Zhang YM, Rock CO, Jackowski S. Biochemical properties of human pantothenate kinase 2 isoforms and mutations linked to pantothenate kinase-associated neurodegeneration. J Biol Chem. 2006 Jan 6;281(1):107-14. doi: 10.1074/jbc.M508825200. Epub 2005 Nov 3. Citation on PubMed
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