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Genetics Home Reference: your guide to understanding genetic conditions
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LRRK2

Reviewed May 2012

What is the official name of the LRRK2 gene?

The official name of this gene is “leucine-rich repeat kinase 2.”

LRRK2 is the gene's official symbol. The LRRK2 gene is also known by other names, listed below.

What is the normal function of the LRRK2 gene?

The LRRK2 gene provides instructions for making a protein called dardarin. The LRRK2 gene is active in the brain and other tissues throughout the body.

One segment of the dardarin protein is called a leucine-rich region because it contains a large amount of a protein building block (amino acid) known as leucine. Proteins with leucine-rich regions appear to play a role in activities that require interactions with other proteins, such as transmitting signals or helping to assemble the cell's structural framework (cytoskeleton). Other parts of the dardarin protein are also thought to be involved in protein-protein interactions.

Additional studies indicate that dardarin has an enzyme function known as kinase activity. Proteins with kinase activity assist in the transfer of a phosphate group (a cluster of oxygen and phosphorus atoms) from the energy molecule ATP to amino acids in certain proteins. This phosphate transfer is called phosphorylation, and it is an essential step in turning on and off many cell activities. Dardarin also has a second enzyme function referred to as a GTPase activity. This activity is associated with a region of the protein called the ROC domain. The ROC domain may help control the overall shape of the dardarin protein.

Does the LRRK2 gene share characteristics with other genes?

The LRRK2 gene belongs to a family of genes called PARK (Parkinson disease).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the LRRK2 gene related to health conditions?

Parkinson disease - caused by mutations in the LRRK2 gene

Researchers have identified more than 100 LRRK2 gene mutations in families with late-onset Parkinson disease (the most common form of the disorder, which appears after age 50). These mutations replace single amino acids in the dardarin protein, which affects the protein's structure and function. It is unclear how LRRK2 gene mutations lead to the movement and balance problems characteristic of Parkinson disease.

A mutation that replaces the amino acid arginine with the amino acid glycine at protein position 1441 (written as Arg1441Gly or R1441G) is a relatively common cause of Parkinson disease in the Basque region between France and Spain. The protein name dardarin comes from the Basque word "dardara," which means tremor, a characteristic feature of Parkinson disease.

Studies of several different populations from around the world revealed a common LRRK2 gene mutation in 3 to 7 percent of familial Parkinson disease cases. This mutation replaces the amino acid glycine with the amino acid serine at protein position 2019 (written as Gly2019Ser or G2019S). The incidence of the Gly2019Ser mutation in familial cases is highest among Arabs from North Africa and people of Ashkenazi (eastern and central European) Jewish ancestry, and it is lowest in Asian and northern European populations. This particular mutation has also been reported in 1 to 3 percent of sporadic Parkinson disease cases, in which there is no family history of the disease.

Studies in Chinese and Japanese populations have identified an LRRK2 gene mutation that occurs more frequently in people with Parkinson disease than in people without the disease. This mutation replaces the amino acid glycine with the amino acid arginine at protein position 2385 (written as Gly2385Arg or G2385R). This mutation appears to increase the risk of Parkinson disease among people in these populations.

Where is the LRRK2 gene located?

Cytogenetic Location: 12q12

Molecular Location on chromosome 12: base pairs 40,225,010 to 40,369,284

The LRRK2 gene is located on the long (q) arm of chromosome 12 at position 12.

The LRRK2 gene is located on the long (q) arm of chromosome 12 at position 12.

More precisely, the LRRK2 gene is located from base pair 40,225,010 to base pair 40,369,284 on chromosome 12.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about LRRK2?

You and your healthcare professional may find the following resources about LRRK2 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the LRRK2 gene or gene products?

  • DRDN
  • LRRK2_HUMAN
  • PARK8
  • RIPK7
  • ROCO2

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding LRRK2?

acids ; amino acid ; arginine ; ATP ; cell ; cytoskeleton ; domain ; enzyme ; familial ; family history ; gene ; glycine ; incidence ; kinase ; leucine ; molecule ; mutation ; oxygen ; phosphate ; phosphorus ; phosphorylation ; protein ; serine ; sporadic ; tremor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bonifati V. LRRK2 low-penetrance mutations (Gly2019Ser) and risk alleles (Gly2385Arg)-linking familial and sporadic Parkinson's disease. Neurochem Res. 2007 Oct;32(10):1700-8. Epub 2007 Apr 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17440812?dopt=Abstract)
  • Cookson MR. The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease. Nat Rev Neurosci. 2010 Dec;11(12):791-7. doi: 10.1038/nrn2935. Epub 2010 Nov 19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21088684?dopt=Abstract)
  • Di Fonzo A, Rohé CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N, Goldwurm S, Breedveld G, Sampaio C, Meco G, Barbosa E, Oostra BA, Bonifati V; Italian Parkinson Genetics Network. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet. 2005 Jan 29-Feb 4;365(9457):412-5. (http://www.ncbi.nlm.nih.gov/pubmed/15680456?dopt=Abstract)
  • Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP, Lynch J, Healy DG, Holton JL, Revesz T, Wood NW. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet. 2005 Jan 29-Feb 4;365(9457):415-6. (http://www.ncbi.nlm.nih.gov/pubmed/15680457?dopt=Abstract)
  • Guo L, Wang W, Chen SG. Leucine-rich repeat kinase 2: relevance to Parkinson's disease. Int J Biochem Cell Biol. 2006;38(9):1469-75. Epub 2006 Mar 2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16600664?dopt=Abstract)
  • Kumar A, Cookson MR. Role of LRRK2 kinase dysfunction in Parkinson disease. Expert Rev Mol Med. 2011 Jun 13;13:e20. doi: 10.1017/S146239941100192X. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21676337?dopt=Abstract)
  • Lesage S, Dürr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, Pollak P, Brice A; French Parkinson's Disease Genetics Study Group. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N Engl J Med. 2006 Jan 26;354(4):422-3. (http://www.ncbi.nlm.nih.gov/pubmed/16436781?dopt=Abstract)
  • Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci. 2006 May;29(5):286-93. Epub 2006 Apr 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16616379?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/120892)
  • Ozelius LJ, Senthil G, Saunders-Pullman R, Ohmann E, Deligtisch A, Tagliati M, Hunt AL, Klein C, Henick B, Hailpern SM, Lipton RB, Soto-Valencia J, Risch N, Bressman SB. LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N Engl J Med. 2006 Jan 26;354(4):424-5. (http://www.ncbi.nlm.nih.gov/pubmed/16436782?dopt=Abstract)
  • Ross OA, Soto-Ortolaza AI, Heckman MG, Aasly JO, Abahuni N, Annesi G, Bacon JA, Bardien S, Bozi M, Brice A, Brighina L, Van Broeckhoven C, Carr J, Chartier-Harlin MC, Dardiotis E, Dickson DW, Diehl NN, Elbaz A, Ferrarese C, Ferraris A, Fiske B, Gibson JM, Gibson R, Hadjigeorgiou GM, Hattori N, Ioannidis JP, Jasinska-Myga B, Jeon BS, Kim YJ, Klein C, Kruger R, Kyratzi E, Lesage S, Lin CH, Lynch T, Maraganore DM, Mellick GD, Mutez E, Nilsson C, Opala G, Park SS, Puschmann A, Quattrone A, Sharma M, Silburn PA, Sohn YH, Stefanis L, Tadic V, Theuns J, Tomiyama H, Uitti RJ, Valente EM, van de Loo S, Vassilatis DK, Vilariño-Güell C, White LR, Wirdefeldt K, Wszolek ZK, Wu RM, Farrer MJ; Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium. Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study. Lancet Neurol. 2011 Oct;10(10):898-908. doi: 10.1016/S1474-4422(11)70175-2. Epub 2011 Aug 30. Erratum in: Lancet Neurol. 2011 Oct;10(10):870. (http://www.ncbi.nlm.nih.gov/pubmed/21885347?dopt=Abstract)
  • Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y, West AB, Dawson VL, Dawson TM, Ross CA. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18676-81. Epub 2005 Dec 13. (http://www.ncbi.nlm.nih.gov/pubmed/16352719?dopt=Abstract)
  • Tan EK, Zhao Y, Skipper L, Tan MG, Di Fonzo A, Sun L, Fook-Chong S, Tang S, Chua E, Yuen Y, Tan L, Pavanni R, Wong MC, Kolatkar P, Lu CS, Bonifati V, Liu JJ. The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence. Hum Genet. 2007 Feb;120(6):857-63. Epub 2006 Sep 30. (http://www.ncbi.nlm.nih.gov/pubmed/17019612?dopt=Abstract)
  • West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16842-7. Epub 2005 Nov 3. (http://www.ncbi.nlm.nih.gov/pubmed/16269541?dopt=Abstract)
  • Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Müller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004 Nov 18;44(4):601-7. (http://www.ncbi.nlm.nih.gov/pubmed/15541309?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2012
Published: July 21, 2014