PINK1 gene
PTEN induced kinase 1
The PINK1 gene provides instructions for making a protein called PTEN induced putative kinase 1. This protein is found in cells throughout the body, with highest levels in the heart, muscles, and testes. Within cells, the protein is located in the mitochondria, the energy-producing centers that provide power for cellular activities. The function of PTEN induced putative kinase 1 is not fully understood. It appears to help protect mitochondria from malfunctioning during periods of cellular stress, such as unusually high energy demands.
Researchers believe that two specialized regions of PTEN induced putative kinase 1 are essential for the protein to function properly. One region, called the mitochondrial-targeting motif, serves as a delivery address: after the protein is made, this motif helps ensure that it is delivered to the mitochondria. Another region, called the kinase domain, probably carries out the protein's protective function.
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Researchers have identified more than 70 mutations in the PINK1 gene that can cause Parkinson disease, a condition characterized by progressive problems with movement and balance. PINK1 gene mutations are associated with the early-onset form of the disorder, which typically begins before age 50.
Many PINK1 gene mutations alter or eliminate the kinase domain, leading to a loss of protein function. At least one mutation affects the mitochondrial-targeting motif and may disrupt delivery of the protein to mitochondria. With reduced or absent PTEN induced putative kinase 1 activity, mitochondria may malfunction, particularly when cells are stressed. Cells can die if energy is not provided for essential activities. It is unclear how PINK1 gene mutations cause the selective death of nerve cells that characterizes Parkinson disease. The loss of these cells weakens communication between the brain and muscles, and ultimately the brain becomes unable to control muscle movement.
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Cytogenetic Location: 1p36.12, which is the short (p) arm of chromosome 1 at position 36.12
Molecular Location: base pairs 20,633,455 to 20,651,511 on chromosome 1 (Homo sapiens Annotation Release 109, GRCh38.p12) (NCBI)
Related Information
- BRPK
- PARK6
- PINK1_HUMAN
- PTEN induced putative kinase 1
Related Information
- Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. Review.
- Beilina A, Van Der Brug M, Ahmad R, Kesavapany S, Miller DW, Petsko GA, Cookson MR. Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5703-8. Epub 2005 Apr 11.
- Chu CT. A pivotal role for PINK1 and autophagy in mitochondrial quality control: implications for Parkinson disease. Hum Mol Genet. 2010 Apr 15;19(R1):R28-37. doi: 10.1093/hmg/ddq143. Epub 2010 Apr 12. Review.
- Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006 Jun 29;441(7097):1162-6. Epub 2006 May 3.
- Hatano Y, Li Y, Sato K, Asakawa S, Yamamura Y, Tomiyama H, Yoshino H, Asahina M, Kobayashi S, Hassin-Baer S, Lu CS, Ng AR, Rosales RL, Shimizu N, Toda T, Mizuno Y, Hattori N. Novel PINK1 mutations in early-onset parkinsonism. Ann Neurol. 2004 Sep;56(3):424-7. Erratum in: Ann Neurol. 2004 Oct;56(4):603.
- Ibáñez P, Lesage S, Lohmann E, Thobois S, De Michele G, Borg M, Agid Y, Dürr A, Brice A; French Parkinson's Disease Genetics Study Group. Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa. Brain. 2006 Mar;129(Pt 3):686-94. Epub 2006 Jan 9.
- Nuytemans K, Theuns J, Cruts M, Van Broeckhoven C. Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum Mutat. 2010 Jul;31(7):763-80. doi: 10.1002/humu.21277. Review.
- Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006 Jun 29;441(7097):1157-61. Epub 2006 May 3.
- Pogson JH, Ivatt RM, Whitworth AJ. Molecular mechanisms of PINK1-related neurodegeneration. Curr Neurol Neurosci Rep. 2011 Jun;11(3):283-90. doi: 10.1007/s11910-011-0187-x. Review.
- Rogaeva E, Johnson J, Lang AE, Gulick C, Gwinn-Hardy K, Kawarai T, Sato C, Morgan A, Werner J, Nussbaum R, Petit A, Okun MS, McInerney A, Mandel R, Groen JL, Fernandez HH, Postuma R, Foote KD, Salehi-Rad S, Liang Y, Reimsnider S, Tandon A, Hardy J, St George-Hyslop P, Singleton AB. Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease. Arch Neurol. 2004 Dec;61(12):1898-904.
- Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G. Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet. 2005 Nov 15;14(22):3477-92. Epub 2005 Oct 5.
- Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, González-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004 May 21;304(5674):1158-60. Epub 2004 Apr 15.
- Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE, Caputo V, Romito L, Albanese A, Dallapiccola B, Bentivoglio AR. PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol. 2004 Sep;56(3):336-41.