What you carry at this position in your DNA and what research says about it.
Parkinson Disease Risk: 10/10 evidence, 28 publications.
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Sample genotype (not yours): T/T
Typical Parkinson Disease Risk
Two copies of the typical gene sequence support normal lysosomal function. This genotype is associated with a baseline risk of developing Parkinson's disease.
What this genotype means: Normal lysosomal pH regulation; Typical baseline risk of Parkinson's disease; Typical age of symptom onset.
Sample genotype (not yours): C/C
Increased Parkinson Disease Risk
Two copies of the threonine variant significantly lower lysosomal channel activity. This genotype is associated with a higher risk of Parkinson's disease and earlier onset.
What this genotype means: Impaired lysosomal waste clearance and pH regulation; Elevated risk of Parkinson's disease and Lewy body dementia; Earlier age of neurodegenerative symptom onset.
Sample genotype (not yours): T/C
Slightly Increased Parkinson Disease Risk
Carrying one copy of the threonine variant moderately reduces lysosomal channel efficiency. This genotype is linked to a slightly higher risk of Parkinson's disease.
What this genotype means: Slightly reduced lysosomal waste clearance; Moderately elevated risk of Parkinson's disease; Slightly earlier potential age of onset.
Gene function and biological role
Gene Function: The TMEM175 gene encodes a proton-selective potassium channel located on the membrane of lysosomes, which are the recycling centers of cells. This channel plays a critical role in maintaining the stable, acidic pH required for lysosomal enzymes to function properly. When lysosomal pH is disrupted, cells cannot efficiently clear metabolic waste and damaged proteins. In neurons, this clearance mechanism is vital for preventing the toxic buildup of proteins like alpha-synuclein, which is a hallmark of neurodegenerative processes. Consequently, genetic variations that impair this gene's function are heavily implicated in the development of movement and cognitive disorders.
Variant Impact: The rs34311866 variant is a missense mutation that changes the amino acid at position 393 of the TMEM175 protein from methionine to threonine. This structural alteration reduces the flow of potassium currents through the lysosomal membrane channel. As a result, lysosomes struggle to regulate their internal acidity, especially during periods of cellular stress or starvation. The impaired waste-disposal capacity leads to an increased accumulation of phosphorylated alpha-synuclein in brain cells. This specific molecular defect is recognized as one of the most significant genetic drivers of Parkinson's disease risk on chromosome 4.
Key Insight: A single amino acid change in this lysosomal channel directly impairs the brain's ability to clear toxic protein clumps, accelerating the cellular aging process that leads to neurodegeneration.
Location: TMEM175. Chromosome 4 · 4p16.3 · 1.0 Mb
Estimated prevalence by population
Global 74.3%; European 66.2%; African 93.8%; East Asian 74.3%; South Asian 46.2%; Americas 80.6%; Ashkenazi 49.0%; Finnish 63.7%; Middle Eastern 66.1%; Amish 59.0%.
Estimated TT genotype frequency.
Global 23.1%; European 30.3%; African 6.1%; East Asian 23.8%; South Asian 43.5%; Americas 18.4%; Ashkenazi 42.0%; Finnish 32.3%; Middle Eastern 30.4%; Amish 35.6%.
Estimated TC genotype frequency.
Global 2.6%; European 3.5%; African 0.1%; East Asian 1.9%; South Asian 10.3%; Americas 1.0%; Ashkenazi 9.0%; Finnish 4.1%; Middle Eastern 3.5%; Amish 5.4%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Neurology & Mental Health
Neurodegenerative Diseases
Parkinson's Disease. Evidence: 10/10. Source: PMID 25064009. Typical Risk.
Lewy Body Dementia. Evidence: 6/10. Source: PMID 35729600. Typical Risk.
Age of Parkinson's Onset. Evidence: 10/10. Source: PMID 30957308. Typical Age.
Sleep & Circadian Rhythm
REM Sleep Behavior Disorder. Evidence: 7/10. Source: PMID 36470867. Typical Risk.
Cardiovascular & Metabolic
Obesity & Body Composition
Waist-to-Hip Ratio. Evidence: 9/10. Source: PMID 30239722. Typical Ratio.
Showing effects for C/C genotype
Parkinson's Disease. Evidence: 10/10. Source: PMID 25064009. ~1.5x Higher Risk.
Lewy Body Dementia. Evidence: 6/10. Source: PMID 35729600. Increased Risk.
Age of Parkinson's Onset. Evidence: 10/10. Source: PMID 30957308. Earlier Onset.
REM Sleep Behavior Disorder. Evidence: 7/10. Source: PMID 36470867. Increased Risk.
Waist-to-Hip Ratio. Evidence: 9/10. Source: PMID 30239722. Higher Ratio.
Showing effects for T/C genotype
Parkinson's Disease. Evidence: 10/10. Source: PMID 25064009. ~1.25x Higher Risk.
REM Sleep Behavior Disorder. Evidence: 7/10. Source: PMID 36470867. ~1.22x Higher Risk.
Waist-to-Hip Ratio. Evidence: 9/10. Source: PMID 30239722. Slightly Higher.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Lysosomal function remains fully efficient with two copies of the reference methionine amino acid. The cellular recycling machinery successfully regulates internal acidity, preventing the abnormal accumulation of toxic proteins in neurons. Large-scale genomic studies confirm that this typical genotype does not carry the elevated risk of neurodegenerative conditions seen in variant carriers. If Parkinson's disease does develop, individuals with this baseline genotype tend to experience a later age of onset compared to those carrying the risk variant. Maintaining healthy cellular habits, such as regular exercise and a balanced diet, continues to support overall brain health.
Normal lysosomal pH regulation; Typical baseline risk of Parkinson's disease; Typical age of symptom onset.
Sample genotype: CC (Homozygous)
Having two copies of the threonine variant leads to a pronounced reduction in lysosomal potassium channel currents. The resulting instability in lysosomal pH severely limits the cell's ability to clear damaged proteins, accelerating the accumulation of toxic alpha-synuclein aggregates in the brain. This genotype is strongly linked to an increased risk of developing Parkinson's disease, with studies indicating a higher odds ratio than single-copy carriers. It also elevates the risk of developing Lewy body dementia and REM sleep behavior disorder. Furthermore, individuals with this genotype who develop Parkinson's tend to experience symptoms at an earlier age.
Impaired lysosomal waste clearance and pH regulation; Elevated risk of Parkinson's disease and Lewy body dementia; Earlier age of neurodegenerative symptom onset.
Sample genotype: TC (Heterozygous)
A single copy of the threonine variant causes a partial reduction in lysosomal potassium currents. This subtle channel impairment makes it slightly harder for brain cells to maintain optimal lysosomal acidity under stress, leading to a gradual buildup of alpha-synuclein proteins. Clinical studies show that carrying one copy of this variant increases the odds of developing Parkinson's disease by approximately 1.25 times. It is also associated with a slightly higher risk of related conditions, such as REM sleep behavior disorder. Additionally, when neurodegenerative symptoms do occur, they may present at an earlier age compared to non-carriers.
Slightly reduced lysosomal waste clearance; Moderately elevated risk of Parkinson's disease; Slightly earlier potential age of onset.
Variants with shared genetic architecture
rs76763715 · GBA1 Gene · Chr 1 · Gaucher Disease
rs11172113 · LRP1 Gene · Chr 12 · Vascular Health
rs11218343 · SORL1 Gene · Chr 11 · Alzheimer's Risk
Content updated August 2026.
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