GBA1 rs76725542: Understanding the N370S Variant
The GBA1 variant rs76725542, widely known as N370S or p.Asn409Ser, is a genetic change in the GBA1 gene. It is the most frequent cause of Type 1 Gaucher disease and is recognized as a significant genetic risk factor for developing Parkinson disease.
What each genotype means
Typical GBA1 function
This genotype represents the most common, non-variant form of the GBA1 gene. Individuals with this profile do not carry the specific N370S mutation associated with increased risk for Gaucher disease or Parkinson disease. This is considered the standard genetic baseline for this location in the gene.
This is the most common genotype found in the vast majority of the global population.
Increased Parkinson disease risk
This genotype indicates you are a carrier of the N370S (p.Asn409Ser) variant in the GBA1 gene. Research shows that carriers of this variant have a statistically higher lifetime risk of developing Parkinson disease compared to non-carriers, and it is the most frequent genetic risk factor for this condition. Please discuss these findings with a genetic counselor or your physician to understand your personal health context.
Carried by approximately 3-4% of the Ashkenazi Jewish population and less than 0.1% of other global ancestries.
Gaucher disease risk
This genotype indicates you carry two copies of the N370S variant, which is associated with Type 1 Gaucher disease. While this condition is often manageable, it can lead to a range of clinical symptoms, and individuals with this genotype also have an increased risk for Parkinson disease. You should consult with a medical specialist, such as a geneticist or neurologist, to discuss clinical monitoring and health management.
This genotype is rare, occurring primarily in individuals of Ashkenazi Jewish descent.
What is the rs76725542 Variant?
The variant rs76725542 is a specific change in the DNA sequence of the GBA1 gene. In scientific literature, it is frequently referred to as N370S, reflecting the substitution of the amino acid asparagine (N) with serine (S) at position 370 of the protein. More recent nomenclature often refers to this as p.Asn409Ser due to changes in how the protein sequence is numbered. This variant is a missense mutation, meaning it results in the production of a protein with a single altered amino acid. Because this change can affect the stability and function of the resulting enzyme, it has been the subject of extensive clinical research regarding its impact on human health, particularly in relation to lysosomal storage disorders and neurodegenerative conditions.
The Role of the GBA1 Gene
The GBA1 gene provides instructions for producing an enzyme called acid beta-glucosidase, also known as glucocerebrosidase. This enzyme resides in lysosomes, which are the cell's recycling centers. Its primary job is to break down a fatty substance called glucocerebroside into simpler sugars and fats. When the GBA1 gene contains certain variants, the resulting enzyme may be misfolded or have reduced activity. This leads to the accumulation of glucocerebroside within cells, which can interfere with normal cellular function. In the context of the nervous system, this accumulation is hypothesized to contribute to the cellular stress and protein aggregation processes that are characteristic of Parkinson disease, though the exact biological mechanisms linking GBA1 activity to neurodegeneration remain an active area of scientific investigation.
Research and Clinical Associations
Research has established a strong link between rs76725542 and Gaucher disease, an autosomal recessive condition. Individuals who inherit two copies of this variant (one from each parent) are at risk for Type 1 Gaucher disease. Beyond this, the variant is a well-documented risk factor for Parkinson disease. Studies indicate that individuals who carry even a single copy of this variant have an increased statistical risk of developing Parkinson disease compared to the general population. However, it is important to note that carrying this variant does not guarantee the development of any disease. The penetrance—the likelihood that a person with the variant will show symptoms—is considered reduced, meaning many carriers may never develop Parkinson disease. The evidence for this association is robust, though researchers continue to study why some carriers are affected while others remain asymptomatic.
Population Frequency
The frequency of the rs76725542 variant varies significantly across different ancestral groups. It is most prevalent in the Ashkenazi Jewish population, where the carrier frequency is approximately 3% to 4%. In contrast, the variant is much rarer in other global populations, with a frequency of less than 0.1%. Because of this distribution, much of the foundational research on this variant has been conducted within Ashkenazi Jewish cohorts. These population-specific differences highlight the importance of considering ancestry when interpreting genetic information. While the variant is a known risk factor, its rarity in the general global population means that it is not a common cause of Parkinson disease for the majority of people worldwide.
Interpreting Your Genetic Information
If you have received information about your status regarding rs76725542, it is essential to understand that this is a statistical association, not a medical diagnosis. Genetic testing can identify the presence of the variant, but it cannot predict with certainty whether an individual will develop a condition like Parkinson disease. Many factors, including other genetic influences, environmental exposures, and lifestyle, contribute to the development of complex diseases. This information should not be used to make personal health decisions without professional guidance. If you are concerned about your genetic risk or family history, the most appropriate step is to consult with a certified genetic counselor or a neurologist. They can help you interpret your results in the context of your personal and family medical history and discuss any appropriate clinical follow-up.
How common is this variant?
The carrier frequency for this variant is approximately 3-4% in Ashkenazi Jewish populations and less than 0.1% in other global ancestries.
Frequently asked questions
Does having the N370S variant mean I will get Parkinson disease?
No, having the variant does not mean you will develop Parkinson disease. It is considered a risk factor, meaning it increases the statistical likelihood, but many carriers never develop the condition.
What is the difference between Gaucher disease and Parkinson disease?
Gaucher disease is a lysosomal storage disorder caused by having two copies of a pathogenic GBA1 variant. Parkinson disease is a neurodegenerative condition that has been statistically linked to carrying one or more GBA1 variants.
Should I get tested for the GBA1 N370S variant?
Genetic testing is a personal decision that should be discussed with a healthcare provider or a genetic counselor. They can help you understand the implications of testing based on your family history and personal health goals.
Is there a cure for GBA1-associated Parkinson disease?
Currently, there is no cure for Parkinson disease, though various treatments exist to manage symptoms. Research into therapies specifically targeting GBA1-related pathways is ongoing.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Also known as the N370S (p.Asn409Ser) mutation, this missense variant is a classic cause of Gaucher disease type 1 in homozygotes and significantly elevates Parkinson's disease risk in heterozygotes.
A variant in the GBA1 gene associated with Gaucher disease and increased risk for Parkinson's disease.
Pathogenic missense substitution (p.Leu483Pro / L444P) in GBA1 associated with Gaucher disease.
Pathogenic missense substitution (p.Asn409Ser) conferring carrier status for Gaucher disease type 1.
A pathogenic missense variant (p.Leu483Pro, legacy L444P) in GBA1 determining carrier status for Gaucher disease and acting as a susceptibility risk factor for Parkinson disease.
Pathogenic variant (c.84dupG) causing severe deficiency in glucocerebrosidase activity, associated with Gaucher disease.