LRRK2
Leucine-rich Repeat Kinase 2
Gene Number: 120892
Location: 12q12
Key Functions: Cell signaling, intracellular transport, cellular recycling, immune regulation
LRRK2 produces leucine-rich repeat kinase 2, an enzyme that helps control cell activity by attaching phosphate groups to other proteins. It operates in nerve cells and immune cells, connecting processes involved in cellular transport, recycling and inflammation [R].
This report examines rs34637584 (G2019S), a pathogenic variant associated with substantially increased Parkinson’s disease risk, and rs33995883 (N2081D), a susceptibility variant studied in Crohn’s disease and Parkinson’s disease.
Explore your genotypes below, or visit SNCA and alpha-synuclein and NOD2 and Crohn’s disease for related genetic findings.
SNP ID | Your Genotype | Alt Allele | Interpretation |
|---|---|---|---|
rs34637584 | Analyze your DNA to see your genotype | A | Analyze your DNA to see a personalized result. |
rs33995883 | Analyze your DNA to see your genotype | G | Analyze your DNA to see a personalized result. |
rs34637584 — G2019S and Parkinson’s Disease
GG – G2019S not detected. No increased risk attributable to this variant. Other genetic and environmental factors still influence Parkinson’s risk.
AG – Significantly increased Parkinson’s disease risk. G2019S is a pathogenic variant with age-dependent, incomplete penetrance: some carriers develop Parkinson’s disease, while others remain unaffected.
AA – Significantly increased Parkinson’s disease risk. This uncommon genotype also carries G2019S. Available evidence does not support assuming twice the risk of AG.
How High Is the Risk?
A 2025 study estimated that approximately 24% of G2019S carriers developed Parkinson’s disease by age 80, compared with approximately 2% of participants carrying neither of the two variants studied. An earlier 2024 study estimated 49% by age 80. Differences in recruitment and the inclusion of unaffected carriers help explain these estimates [R, R]. These figures describe cumulative risk by that age, rather than an annual risk or a certainty of developing the disease.
Functional effect: G2019S replaces glycine with serine at position 2019, increasing LRRK2 kinase activity. This changes signaling involved in intracellular transport and cellular maintenance [R].
rs33995883 — N2081D and Crohn’s Disease
AA – Reference genotype. N2081D is not detected.
AG – Increased Crohn’s disease risk. A smaller association with Parkinson’s disease has also been reported.
GG – Carries the Crohn’s-associated N2081D variant. Evidence is insufficient to assign a reliable, separate GG risk estimate.
A 2018 study reported Crohn’s disease association estimates of OR 1.6–1.7, alongside smaller Parkinson’s estimates of OR 1.1–1.3, across the populations studied. These are variant-level associations, not separate AG and GG predictions [R].
Functional effect: N2081D replaces asparagine with aspartate at position 2081. Laboratory research shows increased activity toward RAB10, a protein involved in cellular transport, and altered inflammatory responses. It is a susceptibility variant, rather than an established cause of inherited Parkinson’s disease like G2019S [R].
If G2019S Appears in Your Results
An AG or AA result at rs34637584 should be confirmed through clinical genetic testing before medical decisions. A genetics professional can interpret a confirmed result alongside your age and family history. GG does not exclude other LRRK2 pathogenic variants or other causes of Parkinson’s disease.
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