GBA1 rs76756627: What Your Genotype Means
The GBA1 rs76756627 variant, commonly known as N370S or p.Asn409Ser, is a genetic change in the GBA1 gene. It is a well-documented cause of Gaucher disease type 1 when inherited in two copies and is associated with an increased risk of developing Parkinson's disease in individuals who carry at least one copy.
What each genotype means
Gaucher disease type 1 risk
Carrying two copies of the variant allele (historically designated N370S or p.Asn409Ser) leads to significantly reduced glucocerebrosidase enzyme activity. This homozygous state is a well-established cause of Gaucher disease type 1 and is also associated with an increased statistical risk of Parkinson's disease. Clinical presentation can range from very mild or asymptomatic to systemic involvement, reflecting incomplete penetrance.
Very rare globally (less than 0.01%), but found in approximately 0.1% to 0.2% of individuals of Ashkenazi Jewish ancestry due to founder effects.
Carrier with elevated Parkinson's risk
Carrying one copy of the variant allele makes you a carrier for Gaucher disease type 1, which typically does not cause Gaucher symptoms on its own. However, published genomic research indicates that heterozygous carriers have an approximately several-fold increased statistical risk of developing Parkinson's disease compared to non-carriers. Because most carriers never develop Parkinson's disease, this variant is a susceptibility factor rather than a direct diagnosis.
Carried by approximately 3% to 6% of people of Ashkenazi Jewish ancestry, but observed in fewer than 0.1% of individuals across most other global populations.
Typical risk profile
You carry two copies of the common reference allele and do not have the N370S (p.Asn409Ser) alteration in the GBA1 gene. You are not at an increased genetic risk for Gaucher disease or Parkinson's disease associated with this specific variant. Your baseline risk for these conditions remains consistent with general population averages.
Found in more than 99.8% of individuals globally, and in roughly 94% to 97% of individuals of Ashkenazi Jewish ancestry.
Understanding the Variant
The variant rs76756627, historically referred to as N370S, is a missense mutation located within the GBA1 gene. In this specific genetic change, the amino acid asparagine is replaced by serine at position 409 of the protein (p.Asn409Ser). This variant is categorized as a pathogenic mutation in the context of Gaucher disease, a lysosomal storage disorder. Because the GBA1 gene is located near a highly homologous pseudogene called GBAP, genetic testing for this variant can be technically complex. Researchers have studied this variant extensively because it provides critical insights into how lysosomal function relates to neurodegenerative conditions. It is important to note that while the variant is well-characterized, the clinical expression can vary significantly between individuals, even among those with the same genotype.
The Role of the GBA1 Gene
The GBA1 gene provides instructions for producing an enzyme called beta-glucocerebrosidase. This enzyme is primarily responsible for breaking down a fatty substance known as glucocerebroside into simpler sugars and fats within lysosomes, which are the recycling centers of the cell. When GBA1 variants like rs76756627 reduce the activity or stability of this enzyme, the substrate can accumulate to toxic levels. In Gaucher disease, this accumulation leads to multi-system health issues. More recently, research has established that even partial reductions in enzyme activity—often seen in individuals who carry only one copy of a pathogenic variant—may contribute to the accumulation of alpha-synuclein, a protein associated with Parkinson's disease and other synucleinopathies. This link highlights the essential role of lysosomal health in maintaining long-term neurological function.
Research and Clinical Associations
The evidence linking rs76756627 to Gaucher disease type 1 is definitive, as it is a classic cause of the condition in homozygous individuals. Regarding Parkinson's disease, the evidence is considered strong for an association with increased risk in heterozygotes, though the penetrance—the likelihood that a carrier will actually develop symptoms—is incomplete. Studies have shown that the frequency of this variant is significantly higher in cohorts of patients with Parkinson's disease compared to healthy control groups. However, it is crucial to understand that carrying this variant does not guarantee the development of Parkinson's disease. Many individuals with this genotype never develop neurological symptoms. Current research is ongoing to determine the additional genetic and environmental factors that influence why some carriers remain healthy while others develop disease.
What This Information Means for You
If you have received information about your status for rs76756627, it is important to view it in the context of your overall health and family history. This variant is not a diagnostic tool for Parkinson's disease; rather, it is a risk factor that researchers use to study disease mechanisms. Because the presence of this variant can have implications for both Gaucher disease and Parkinson's risk, individuals with concerns about their genetic status or family history should consult with a board-certified genetic counselor or a neurologist. These professionals can provide personalized context, explain the limitations of genetic testing, and discuss whether clinical monitoring is appropriate. You should never make medical decisions or changes to your health regimen based solely on a genetic report without professional clinical guidance.
How common is this variant?
The rs76756627 variant is notably enriched in Ashkenazi Jewish populations, where the carrier frequency is approximately 3-6%. It is considered rare, with a frequency of less than 0.1%, in the general global population.
Frequently asked questions
Does having the N370S variant mean I will get Parkinson's disease?
No, having this variant does not mean you will develop Parkinson's 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's disease in relation to GBA1?
Gaucher disease is a lysosomal storage disorder typically caused by inheriting two copies of a GBA1 mutation. Parkinson's disease is a neurodegenerative condition that has been observed at higher rates in individuals who carry one or two copies of certain GBA1 mutations.
Should I get tested for GBA1 variants?
Genetic testing for GBA1 is typically performed in clinical settings for individuals with a family history of Gaucher disease or early-onset Parkinson's. You should discuss the necessity and implications of such testing with a genetic counselor or your physician.
Is there a cure for GBA1-associated conditions?
There are treatments available for the symptoms of Gaucher disease, such as enzyme replacement therapy. Research into therapies for GBA1-associated Parkinson's disease is an active area of clinical investigation, but there is currently no cure.
Sources & further reading
Educational information only, last refreshed 10/11/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.
A pathogenic variant (p.Asn409Ser, formerly N370S) in GBA1 associated with Gaucher disease and increased risk for Parkinson disease.