HIF1A rs11549407: What Your Genotype Means
The rs11549407 single nucleotide polymorphism, commonly known as P582S, is a missense variation in the hypoxia-inducible factor 1-alpha (HIF1A) gene. It alters an amino acid in a vital transcription factor responsible for cellular adaptations to low-oxygen environments. Research has linked this variant to modest differences in the risk of certain cancers and diabetic vascular complications, though the overall clinical evidence remains limited and observational.
What each genotype means
Typical HIF-1α function
You carry two copies of the common C allele, coding for the standard proline residue at position 582 of the HIF-1α protein. This genotype reflects baseline cellular oxygen-sensing and typical transcription of hypoxia-regulated genes. Research on associations with diabetic complications and cancer risk has shown average population baselines for individuals with this genotype.
Carried by approximately 84% to 86% of European populations and upwards of 95% to 98% of East Asian and African ancestry populations.
Altered hypoxia response
You have one copy of the T allele (P582S), which confers enhanced baseline transcriptional activity to the HIF-1α protein under low-oxygen conditions. Published studies suggest this genotype may modestly alter susceptibility to diabetic vascular complications and certain cancers, though findings remain mixed across different ancestral backgrounds. This is a common genetic trait rather than a direct disease cause.
Found in about 13% to 15% of individuals of European ancestry and roughly 2% to 4% of East Asian populations.
Elevated hypoxia-response activity
You carry two copies of the T allele encoding the 582Ser variant of the HIF-1α transcription factor. Having two copies is biologically associated with increased transcriptional activation of hypoxia-inducible target genes. Published clinical association data regarding specific health outcomes or diabetic microvascular risks are limited due to the relative rarity of this homozygous genotype.
Very rare, observed in less than 1% of people of European descent and exceptionally uncommon across other global ancestries.
Genetic Location and Molecular Impact
The rs11549407 polymorphism is located in the coding sequence of the HIF1A gene on human chromosome 14. At the nucleotide level, the variant typically involves a cytosine-to-thymine substitution (c.1744C>T on the canonical transcript), which leads to an amino acid substitution of proline with serine at position 582 (Pro582Ser or P582S). Because this change occurs within the oxygen-dependent degradation domain of the HIF-1α protein, molecular assays have demonstrated that the Ser582 variant can resist degradation under normal oxygen levels compared to the standard Pro582 form. This slight increase in baseline protein stability enhances transcriptional activity at hypoxia response elements, altering downstream cellular programs.
The Biological Role of HIF1A
The HIF1A gene produces the alpha subunit of hypoxia-inducible factor 1 (HIF-1), a primary master regulator of oxygen homeostasis in human tissues. Under normal oxygen concentrations, HIF-1α is continuously hydroxylated and targeted for rapid proteasomal degradation. When oxygen levels drop, degradation stops, allowing HIF-1α to dimerize with HIF-1β and initiate transcription of hundreds of genes involved in angiogenesis, red blood cell production, glucose metabolism, and cell survival. Alterations that modify HIF-1α stability or baseline activity can shift how effectively tissues vascularize in response to ischemic injuries or adapt to the hypoxic cores of growing tumors.
Research Associations and Evidence Strength
Epidemiological and candidate-gene studies have explored rs11549407 in the context of cardiovascular outcomes, diabetic microvascular complications, and several forms of cancer. Because the variant enhances angiogenic signaling, some studies report a protective trend against severe coronary artery disease or ischemic damage, while other meta-analyses link the T allele to modest increases in susceptibility to specific solid malignancies, including head and neck, breast, and renal tumors. However, findings across independent study cohorts remain mixed, with substantial heterogeneity depending on tumor type and study design. Large-scale genome-wide association studies (GWAS) have not established rs11549407 as an independent diagnostic marker, leaving its clinical evidence strength classified as limited.
Population Distribution and Frequency
The distribution of the rs11549407 variant exhibits notable variation across ancestral populations. In European cohorts, the minor T allele typically occurs at frequencies between 6% and 10%, with around 15% to 18% of individuals carrying at least one copy of the variant. In East Asian and African populations, the minor allele is less frequent, generally observed at rates under 2% to 3%. Because genotype frequencies vary considerably around the world, epidemiological risk estimates identified in European study cohorts cannot be directly applied across different geographic ancestries without further stratified replication.
Interpreting Your Results and Actionability
Discovering your rs11549407 genotype provides an educational glimpse into cellular oxygen-sensing pathways, but it is not a clinical test for disease. The presence of the T allele does not cause cancer, nor does the CC genotype confer immunity from vascular diseases. This polymorphism represents one minor factor among tens of thousands of common variants, each exerting a modest influence that is secondary to lifestyle, age, and clinical health measures. Genetic testing results should never be used to make independent medical decisions or modify prescription regimens, which should always be discussed with a qualified healthcare provider.
How common is this variant?
The minor T allele occurs at a frequency of approximately 0.08 in European populations, while appearing at lower frequencies (~0.02) in East Asian and African ancestries.
Frequently asked questions
Does carrying the HIF1A rs11549407 variant mean I will get cancer?
No. Carrying the variant is only associated with modest statistical differences in risk in certain observational studies. It is not a high-penetrance mutation and does not determine whether an individual will develop cancer.
What does the HIF1A gene do in the body?
HIF1A encodes a key subunit of the HIF-1 transcription factor, which serves as a master regulator of cellular oxygen sensing. It turns on specific genes that promote blood vessel formation, energy metabolism, and cell survival when oxygen levels become low.
Can I use my rs11549407 genotype to change my medications?
No. The rs11549407 variant has no approved pharmacogenomic guidelines from organizations like CPIC or PharmGKB. Any adjustments to medications or therapies must always be managed in consultation with your prescribing clinician or pharmacist.
Why are research findings for rs11549407 mixed?
Common complex conditions like cancer and cardiovascular disease involve hundreds of interacting genetic variants alongside environmental and lifestyle factors. Small study sizes and ancestral differences across cohorts often lead to conflicting results in candidate-gene research.
Sources & further reading
Educational information only, last refreshed 9/11/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Functional polymorphism in hypoxia-inducible factor 1-alpha associated with anaerobic power output and muscle performance under hypoxia.
Missense variant (c.1744C>T, p.Pro582Ser) in HIF1A that confers enhanced transcriptional activation under hypoxic conditions, studied in athletic performance, tumor angiogenesis, and ischemic stroke.