SLC6A2 rs28386840: What Your Genotype Means
The rs28386840 variant is a single-nucleotide polymorphism located within the SLC6A2 gene. It has been investigated by researchers for its potential association with how individuals respond to methylphenidate, a medication commonly used to manage ADHD.
What each genotype means
Typical norepinephrine transporter activity
This is the major homozygous genotype for this variant. Research suggests that individuals with this genotype may show a different response to methylphenidate compared to those carrying the T allele, though findings regarding its specific clinical impact remain mixed and controversial. Please discuss any medication-related concerns or dosing questions with your clinician or pharmacist.
This is the most common genotype for this variant in most populations.
Potential increased methylphenidate response
Carrying one copy of the T allele has been associated in some studies with an increased response to methylphenidate in children with ADHD compared to the AA genotype. Because the evidence is limited and results across studies have been inconsistent, this information should not be used to guide clinical decisions. Please consult your healthcare provider or pharmacist regarding your treatment plan.
This genotype is less common than the AA genotype and is considered rare in many populations.
Potential increased methylphenidate response
Carrying two copies of the T allele has been associated in some studies with an increased response to methylphenidate in children with ADHD compared to the AA genotype. As the evidence for this association is limited and sometimes conflicting, it is not a definitive predictor of drug response. Please discuss your medication management and any questions about your treatment with your clinician or pharmacist.
This is a rare genotype across most studied populations.
Understanding the Variant and Its Location
The variant rs28386840 is a single-nucleotide polymorphism (SNP) found on chromosome 16. In the human genome, it is positioned at 55,652,906 (GRCh38). This specific location places it within the SLC6A2 gene, which encodes the norepinephrine transporter (NET). SNPs are the most common type of genetic variation among people, representing a difference in a single DNA building block, or nucleotide. While many SNPs have no effect on health or drug response, researchers study specific variants like rs28386840 to determine if they contribute to the biological diversity observed in how different people process medications or experience symptoms of certain conditions.
The Role of the SLC6A2 Gene
The SLC6A2 gene provides instructions for making the norepinephrine transporter protein. This protein is responsible for clearing norepinephrine, a chemical messenger (neurotransmitter), from the synaptic cleft—the space between nerve cells. By transporting norepinephrine back into the presynaptic neuron, the NET protein helps regulate the amount of this neurotransmitter available to signal between cells. Because norepinephrine plays a key role in attention, focus, and the body's stress response, the SLC6A2 gene is a primary target for medications like methylphenidate and atomoxetine. Variations in this gene may theoretically alter the efficiency of the transporter, potentially influencing how a person's nervous system responds to drugs that modulate norepinephrine levels.
Research and Evidence Strength
The evidence linking rs28386840 to methylphenidate response is currently considered limited. While some studies have explored this variant in the context of ADHD pharmacogenetics, results have been inconsistent. For instance, some research has suggested potential associations with neuropsychological changes, while other studies have found no significant relationship between this specific SNP and treatment outcomes. Because ADHD is a complex condition influenced by many genetic and environmental factors, it is difficult to isolate the effect of a single variant. Current scientific literature does not support using this variant as a definitive predictor of how a patient will respond to medication. Further large-scale, well-controlled studies are required to clarify whether this variant has any clinically meaningful impact.
Population Frequency
The rs28386840 variant is classified as rare. Because it occurs at a low frequency in the general population, it is not commonly encountered in standard genetic screening panels. Data regarding its distribution across different ancestral groups remain sparse, and its rarity makes it challenging for researchers to gather large enough sample sizes to draw definitive conclusions about its prevalence or functional significance in diverse populations.
What This Information Means for You
It is important to understand that genetic variants like rs28386840 are subjects of ongoing scientific research and are not currently used in routine clinical practice to guide medication choices. Having a particular genotype for this variant does not provide a diagnosis or a guaranteed prediction of how you will respond to a specific drug. If you are taking methylphenidate or considering treatment for ADHD, you should never make changes to your medication regimen based on genetic information found online. Always discuss your treatment plan, including any concerns about efficacy or side effects, with your prescribing physician or a qualified pharmacist. They are the only ones who can provide medical advice tailored to your specific health history and clinical needs.
How common is this variant?
The rs28386840 variant is considered rare across most populations, with limited data available regarding its specific frequency in diverse ancestral groups.
Frequently asked questions
Can I use a genetic test to see if methylphenidate will work for me?
Currently, there is no widely accepted genetic test that can definitively predict your response to methylphenidate. While researchers study variants like rs28386840, these findings are not yet robust enough for clinical use.
Is rs28386840 a diagnostic marker for ADHD?
No, rs28386840 is not a diagnostic marker for ADHD. ADHD is a complex condition diagnosed by clinicians based on behavioral symptoms and clinical history, not by genetic testing.
Should I change my ADHD medication based on my SLC6A2 genotype?
No. You should never change your medication or dosage based on genetic test results without consulting your doctor. Medication management should be based on your clinical response and side-effect profile under medical supervision.
Where can I find more information about pharmacogenetics?
You can find reliable information on pharmacogenetics through resources like the Clinical Pharmacogenetics Implementation Consortium (CPIC) or the PharmGKB database. These organizations provide evidence-based guidelines for how genetic information may eventually inform drug therapy.
Sources & further reading
Educational information only, last refreshed 10/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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The C/C genotype of this variant is associated with a poorer response to methylphenidate in patients with lower baseline ADHD severity scores.
The G/G genotype of this variant is associated with an improved response to methylphenidate compared to A allele carriers.