DPYD rs55886062: Genetic Variation and Drug Response
The rs55886062 variant is a single-nucleotide polymorphism located in the DPYD gene, classically documented in pharmacogenomics as the c.2846A>T (p.Asp949Val) missense alteration. Carrying this variant leads to a moderate decrease in dihydropyrimidine dehydrogenase enzymatic activity, which alters the rate at which the body breaks down certain anticancer medications. Consequently, carriers face a significantly higher risk of severe or life-threatening adverse reactions when exposed to standard doses of fluoropyrimidine therapies like 5-fluorouracil and capecitabine.
What each genotype means
Normal enzyme activity
This genotype represents the common, wild-type sequence for this position in the DPYD gene. Individuals with this profile are generally expected to have normal dihydropyrimidine dehydrogenase (DPD) enzyme function, though this does not guarantee the absence of toxicity from fluoropyrimidine medications. Always discuss your treatment plan and any potential side effects with your oncologist or pharmacist.
This is the most common genotype found in the vast majority of the global population.
Reduced enzyme activity
This genotype indicates you carry one copy of the DPYD*13 variant (c.1679T>G). Research identifies this as a 'no function' allele, which can lead to partial DPD enzyme deficiency and an increased risk of severe, potentially life-threatening toxicity when treated with fluoropyrimidine drugs like 5-fluorouracil or capecitabine. You should discuss this genetic finding with your clinician before starting any chemotherapy to determine if dose adjustments are necessary.
This genotype is rare, with the variant allele occurring at a frequency of approximately 0.002 to 0.008 in European populations and being very rare in East Asian and African populations.
Significantly reduced enzyme activity
This genotype indicates you carry two copies of the DPYD*13 variant (c.1679T>G). This is associated with a profound reduction or absence of DPD enzyme activity, which significantly increases the risk of severe or fatal toxicity if exposed to standard doses of fluoropyrimidine chemotherapy. It is critical to share this information with your healthcare team immediately so they can consider alternative therapies or specialized dosing strategies.
This homozygous genotype is extremely rare in all known human populations.
Molecular Profile: What Is rs55886062?
The single nucleotide polymorphism designated rs55886062 resides in the DPYD gene on chromosome 1. At this specific genomic coordinate, a substitution replaces an adenine (A) with a thymine (T), documented in standard molecular nomenclature as c.2846A>T. Because this base change occurs within a protein-coding exon, it alters the amino acid sequence from aspartic acid to valine at position 949 (p.Asp949Val). This structural alteration moderately disrupts the folding and catalytic function of the resulting polypeptide chain. In standard pharmacogenetic testing panels, this allele is specifically assayed as one of several core functional variants that predict impaired drug clearance. Unlike complete loss-of-function variants, this missense change causes a partial decrease in enzymatic activity, categorizing it functionally as a decreased-function allele in consensus pharmacogenomic guidelines.
The Biological Role of the DPYD Gene
The DPYD gene provides instructions for producing dihydropyrimidine dehydrogenase (DPD), a critical rate-limiting enzyme responsible for the catabolism of pyrimidine molecules in the human body. Under normal physiological conditions, DPD converts uracil and thymine into inactive breakdown products, maintaining balanced pyrimidine pools. In clinical medicine, the activity of DPD is paramount because it also catabolizes more than eighty percent of administered fluoropyrimidine chemotherapy agents, primarily 5-fluorouracil (5-FU) and its oral prodrug capecitabine. When DPD enzyme activity is compromised, the clearance of these cytotoxic drugs decreases dramatically. Unmetabolized drugs accumulate systemically, exposing healthy tissues throughout the body to toxic chemotherapy levels and predisposing affected patients to severe drug-induced cellular damage.
Clinical Evidence and Chemotherapy Toxicity Risk
Extensive pharmacogenomic literature, including systematic reviews and guidelines from bodies such as the Clinical Pharmacogenetics Implementation Consortium (CPIC), has evaluated the c.2846A>T variant. Multiple clinical trials and meta-analyses indicate that individuals who inherit at least one copy of this alternate allele have a substantially higher probability of suffering grade 3 or higher toxicities. These adverse events characteristically involve life-threatening neutropenia, severe diarrhea, painful mucositis, and hand-foot syndrome when exposed to unadjusted fluoropyrimidine regimens. While some catalog databases grade the single-variant evidence as limited in isolation due to the absolute rarity of homozygous carriers, its collective biological impact within clinical DPYD risk scoring systems is firmly recognized. Carrier screening allows clinicians to calculate an individualized gene activity score and proactively consider alternative therapies or standardized dosage reductions.
Population Frequency and Ancestral Distribution
The rs55886062 variant is relatively uncommon across the global population. Genomic population databases, including gnomAD and the 1000 Genomes Project, demonstrate that the minor T allele is most frequently detected in individuals of European ancestry, with an estimated minor allele frequency between 0.002 and 0.008 (roughly 0.2% to 0.8%). In contrast, this particular variant is exceptionally rare or practically absent in populations of East Asian and African descent. However, clinical researchers emphasize that absence of rs55886062 does not equate to absence of fluoropyrimidine risk in non-European groups. Other distinct decreased-function or null DPYD alleles, such as HapB3, *2A, or ancestry-specific variants, are distributed differently across global ancestries, underscoring the clinical importance of multi-variant pharmacogenomic panels.
Interpreting Genetic Results in Clinical Practice
Genetic findings at rs55886062 provide valuable pharmacogenomic insights, but they do not represent a disease diagnosis or dictate independent action. Having one or more variant alleles does not imply that an individual has cancer or an active illness, as DPD deficiency is typically clinically silent until challenged by specific antimetabolite medications. Conversely, having the typical reference genotype does not guarantee absolute immunity against adverse chemotherapy reactions, as other uncharacterized genetic markers, kidney clearance rates, liver health, and concomitant drugs also modulate toxicity. Patients receiving cancer therapies or preparing for oncologic treatment who discover their rs55886062 genotype should discuss these findings directly with their medical oncologist, clinical geneticist, or pharmacist before adjusting any therapeutic plan.
How common is this variant?
The minor T allele of rs55886062 has a frequency of approximately 0.002 to 0.008 (0.2% to 0.8%) in individuals of European ancestry. It is observed at extremely low frequencies or is virtually undetectable in East Asian and African populations.
Frequently asked questions
Does having the rs55886062 variant mean I have a disease?
No, carrying the rs55886062 variant is not a medical condition and causes no noticeable health problems on its own. It is a pharmacogenomic marker that primarily becomes clinically meaningful if a person is prescribed specific chemotherapy medications, such as 5-fluorouracil or capecitabine.
What happens if a carrier of rs55886062 needs chemotherapy?
If an individual carrying this variant requires treatment with fluoropyrimidines, their oncology team can evaluate the genetic result alongside other laboratory tests. Clinical guidelines often recommend starting with a reduced dose or selecting an alternate therapeutic regimen to mitigate the risk of severe toxicity.
Why is this variant more common in some ancestries than others?
Genetic variants naturally arise and drift in human populations over thousands of years. The rs55886062 variant occurs at a low frequency predominantly in European lineages, whereas other functional DPYD variants are found in populations of African, Asian, or admixed heritage.
Can a normal AA genotype guarantee no side effects from fluorouracil?
No, a typical AA result does not guarantee the absence of side effects. While it lowers the likelihood of toxicity caused by this specific variant, adverse drug events can still stem from other genetic changes, organ function, or non-genetic clinical factors.
Sources & further reading
Educational information only, last refreshed 9/6/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This intronic variant is a marker for reduced DPYD enzyme activity, increasing the risk of severe toxicity from fluoropyrimidine-based chemotherapies.
This variant is linked to decreased dihydropyrimidine dehydrogenase activity, increasing the risk of severe toxicity during fluoropyrimidine chemotherapy.
Defines the DPYD*7 variant (p.Leu311Phe) associated with impaired pyrimidine metabolism and potential fluoropyrimidine toxicity.
Constitutes the DPYD*13 variant (p.Ile560Thr), associated with significantly reduced DPYD enzyme activity and increased risk of severe fluoropyrimidine toxicity.
Also designated as DPYD c.557A>G (p.Tyr186Cys), this variant significantly decreases dihydropyrimidine dehydrogenase activity and predisposes patients to severe fluoropyrimidine toxicity.
A synonymous variant in exon 11 (c.1236G>A) that is in high linkage disequilibrium with the causal intronic variant c.1129-5923C>G (rs75017182), which defines the HapB3 haplotype associated with reduced DPYD activity and fluoropyrimidine toxicity.