Reviewed July 2007
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, but little is known about this gene or the dardarin protein.
Studies of the gene's instructions have revealed some clues about dardarin's function. Part of the LRRK2 gene provides instructions for making a protein segment that is rich in a protein building block (an amino acid) called leucine. Proteins with leucine-rich regions appear to play a role in activities that require protein-protein interactions, such as transmitting signals or helping to assemble the cell's structural framework (cytoskeleton). Other parts of the LRRK2 gene provide instructions for protein regions called the ROC-COR domain and the WD40 domain. These domains also suggest that dardarin is capable of multiple protein-protein interactions.
Additional research findings indicate that dardarin has an enzyme activity known as kinase. Proteins with kinase activity assist in the transfer of a phosphate group (a cluster of oxygen and phosphate 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 may have a second enzyme activity referred to as a GTPase activity. This activity is associated with a region of the protein called the ROC domain. The ROC domain may act as a molecular switch that controls the overall shape of the dardarin protein.
How are changes in the LRRK2 gene related to health conditions?
Parkinson disease - caused by mutations in the LRRK2 gene
Researchers have identified at least 20 LRRK2 mutations in families with late-onset Parkinson disease. These mutations replace one amino acid with another amino acid in the dardarin protein, which affects the protein's structure and function. It is unclear how LRRK2 mutations lead to Parkinson disease.
A mutation that replaces the amino acid arginine with the amino acid glycine at protein position 1396 (written as Arg1396Gly or R1396G) 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 mutation that is found 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 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 38,905,085 to 39,051,869
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 38,905,085 to base pair 39,051,869 on chromosome 12.
See How do geneticists indicate the location of a gene? 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?
Where can I find general information about genes?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding LRRK2?
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
See How can I find a genetics professional in my area? in the Handbook.