SNCA rs356219 and rs11931074: Alpha-Synuclein and Parkinson’s Risk

3 days ago

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The SNCA gene produces alpha-synuclein, a protein involved in communication between nerve cells. It is also a central protein in Parkinson’s disease research because abnormal alpha-synuclein accumulates in structures called Lewy bodies [R].

Two common variants, SNCA rs356219 and rs11931074, have repeatedly been associated with Parkinson’s disease susceptibility. These markers help researchers investigate how inherited variation around an important brain protein relates to disease risk [R, R].

You can explore both markers in the free SNCA GeneExplorer entry.

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What Does the SNCA Gene Do?

Alpha-synuclein is concentrated at presynaptic terminals, the ends of neurons that release chemical messages.

Research suggests it helps maintain the supply of synaptic vesicles—small compartments that store neurotransmitters—and participates in regulating their release. Its normal function therefore concerns how neurons communicate [R]. Problems arise when alpha-synuclein behaves abnormally, including when it misfolds and accumulates. Its involvement in Parkinson’s disease makes SNCA important for understanding both ordinary neuronal function and neurodegeneration.

This connects with the movement-related role of dopamine, explored in our article on dopamine, motivation, reward, and focus.

SNCA rs356219: What Do AA, AG, and GG Mean?

Rs356219 is a noncoding marker near the 3′ end of SNCA. It does not change the amino-acid sequence of alpha-synuclein. Researchers have investigated this region for its relationship with gene regulation and Parkinson’s susceptibility [R].

A 2019 meta-analysis reported the following associations:

Genotype	Parkinson’s disease association
AA	Baseline risk
AG	Approximately 26% higher odds; OR 1.261
GG	Approximately 96% higher odds; OR 1.958

The analysis found associations in both Asian and European-ancestry study groups [R].

GG was associated with nearly twice the odds compared with AA in that pooled analysis. This does not mean a 96% chance of developing Parkinson’s disease. AA is also a comparison genotype, not a guarantee of protection.

SNCA rs11931074: What Do GG, GT, and TT Mean?

Rs11931074 is another noncoding marker in the SNCA region. Here, the T allele has been associated with increased Parkinson’s disease susceptibility.

A 2018 meta-analysis combined 33 studies involving 45,078 participants, including 15,368 people with Parkinson’s disease and 29,710 controls.

Genotype or group	Reported association
GG	Baseline risk
GT or TT combined	Approximately 44% higher odds
TT	Approximately 87% higher odds

Source: [R].

Does the Risk Allele Simply Produce More Alpha-Synuclein?

The biology is more interesting than that simple explanation suggests.

In a study using 228 brain-tissue samples from 144 neurologically unaffected individuals, researchers examined how SNCA variants related to messenger RNA levels.

For rs356219, the AA genotype was associated with approximately 40% higher SNCA messenger RNA in temporal cortex tissue than AG or GG, despite A being the lower-susceptibility allele in disease-association studies. No corresponding genotype association was detected in the frontal cortex [R].

How These Markers Differ From Rare SNCA Pathogenic Variants

Common susceptibility markers are one part of SNCA genetics.

Rare pathogenic variants that alter alpha-synuclein’s protein sequence, along with duplications or triplications of the gene, can cause inherited forms of Parkinson’s disease. Rs356219 and rs11931074 are not equivalent to those findings [R].

Checking these two common markers does not screen for all disease-causing changes in SNCA.

For another important Parkinson’s-related genetic mechanism, see LRRK2 rs34637584, also called G2019S. That article concerns a pathogenic variant with incomplete penetrance, rather than the common susceptibility markers discussed here.

Can You Combine Your Two SNCA Results?

You can read both results together, but do not multiply their odds ratios to calculate personal risk.

These markers sit in the same genetic region and can capture overlapping inherited information. Research examining SNCA alongside other Parkinson’s-related genes has investigated these relationships using statistical models that account for the markers together [R].

For example, multiplying 1.958 by 1.87 would not produce a validated risk estimate for someone with rs356219 GG and rs11931074 TT.

What Your SNCA Result Means for You

These variants are useful for exploring a well-studied connection between genetics and alpha-synuclein biology. A higher-susceptibility genotype means that the genotype occurred more frequently among Parkinson’s cases than controls in the cited research. It does not establish that you currently have the condition. Likewise, rs356219 AA or rs11931074 GG does not rule Parkinson’s disease out. These are reference comparisons for individual markers, not complete assessments of neurological health.

Related genes also answer different questions. For example, DRD2 variants concern dopamine-receptor biology, while SNCA concerns alpha-synuclein and its surrounding regulatory region.

Explore Your SNCA Results in GeneExplorer

SNCA connects everyday communication between neurons with one of the most important proteins in Parkinson’s research. Rs356219 and rs11931074 provide an accessible way to explore that connection, with published genotype comparisons that make the research more tangible.

Visit the free SNCA GeneExplorer entry to explore both markers. You can analyze your existing raw DNA file in your browser to check which supported genotypes are available.