TPCN2 rs35264875: What Your Genotype Means
The rs35264875 variant is a coding missense mutation located within the TPCN2 gene. It is statistically associated with variations in hair pigmentation, specifically contributing to the blonde versus brown hair color phenotype in individuals of European ancestry.
What each genotype means
Typical hair pigmentation
This genotype represents the common, ancestral form of the TPCN2 variant. It is not associated with the specific blonde hair color variation linked to the T allele in European populations.
This is the most common genotype globally, carried by the majority of individuals outside of specific European cohorts.
Potential hair color influence
Carrying one copy of the T allele may contribute to hair pigmentation variation, though the effect is typically more pronounced in individuals who are homozygous for the T allele. Research indicates this variant functions as a gain-of-function mutation in the TPCN2 channel, which influences pigmentation pathways.
This heterozygous genotype is found at moderate frequencies in populations of European descent.
Associated with blonde hair
This genotype is statistically associated with blonde hair color in populations of European descent. The T allele encodes the M484L amino acid change, which acts as a gain-of-function variant in the TPCN2 protein, though its full effect on pigmentation often requires the presence of other specific genetic backgrounds.
The T allele has a minor allele frequency of approximately 0.20 in European cohorts, making this homozygous genotype present in a significant minority of that population.
Understanding the Variant
The rs35264875 variant is a single nucleotide polymorphism (SNP) situated on chromosome 11 at position 69,078,931. In genetic terms, this is a missense variant, meaning the change in the DNA sequence results in a different amino acid being incorporated into the TPCN2 protein. Specifically, this variant leads to an amino acid substitution known as M484L. Because this change occurs within the protein-coding region of the gene, it has the potential to alter the function or regulation of the resulting protein. Researchers track this specific SNP because it serves as a molecular marker that correlates with observable physical traits, particularly those related to human pigmentation.
The Role of TPCN2
The TPCN2 gene encodes a protein called Two Pore Segment Channel 2. This protein functions as an ion channel located within the membranes of intracellular organelles, such as lysosomes. These channels are essential for regulating the movement of ions, which in turn influences various cellular processes. In the context of pigmentation, TPCN2 activity is linked to the regulation of melanin production within melanocytes, the cells responsible for skin, hair, and eye color. Research suggests that the M484L substitution caused by rs35264875 may act as a gain-of-function variant, potentially increasing the channel's sensitivity to internal cellular signals and thereby influencing the final pigment composition of hair follicles.
Research and Evidence
The association between rs35264875 and hair color has been identified through genome-wide association studies (GWAS) and targeted genetic research. Evidence from multiple studies indicates that this variant is one of several genetic factors contributing to the spectrum of hair color in European populations. While the evidence for this association is considered moderate, it is supported by functional studies showing that the variant alters TPCN2 channel activity. It is important to note that hair color is a complex, polygenic trait, meaning it is influenced by the cumulative effect of many different genes, including MC1R, OCA2, and HERC2. Therefore, rs35264875 is only one piece of a much larger genetic puzzle.
Population Frequency
The frequency of the rs35264875 variant varies significantly across different global populations. In cohorts of European descent, the minor allele frequency is approximately 0.20, making it a relatively common variant in these groups. Because genetic diversity is high across the globe, the prevalence of this specific allele may be much lower or entirely absent in other ancestral populations. Understanding these frequency differences is a key component of population genetics, as it helps researchers determine how certain traits became more or less common in specific geographic regions over human history.
Interpreting Your Results
If you have access to your genetic data, you may see your genotype for rs35264875 listed as A/A, A/T, or T/T. It is important to remember that this information is for educational purposes only and cannot be used to predict your physical appearance with absolute certainty, as environmental factors and other genes play significant roles. This variant is not a medical diagnostic tool, and it does not provide information about health risks or disease susceptibility. If you are interested in learning more about your genetic makeup, consider discussing your results with a qualified genetic counselor who can provide context based on your full genetic profile and family history.
How common is this variant?
The minor allele frequency for rs35264875 is approximately 0.20 in European cohorts, though it varies significantly across different global populations.
Frequently asked questions
Does rs35264875 determine my hair color?
No, this variant is only one of many genetic factors that influence hair color. Human pigmentation is a complex, polygenic trait influenced by numerous genes and environmental factors.
Is rs35264875 linked to any health conditions?
Current research primarily associates this variant with hair pigmentation variation. It is not considered a diagnostic marker for any specific medical condition.
Why is this variant common in Europeans?
Genetic variants associated with lighter pigmentation are more frequent in populations with Northern European ancestry. This is often attributed to historical evolutionary pressures related to sunlight exposure and vitamin D synthesis.
Can I change my hair color based on my genotype?
Your genotype is fixed at birth and cannot be changed. While your genetics provide a blueprint for your traits, they do not limit your ability to use cosmetic products to alter your hair color.
Sources & further reading
Educational information only, last refreshed 9/23/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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