MC1R rs1805004: What Your Genotype Means
The single nucleotide polymorphism rs1805004 is a well-known missense variation in the melanocortin 1 receptor (MC1R) gene, causing an Arg160Trp (R160W) amino acid substitution. It is strongly linked to the classic red hair color phenotype, pale skin, freckling, and reduced tanning capacity in individuals of European heritage. As a loss-of-function change in melanin synthesis pathways, it shifts pigment production toward reddish-yellow pheomelanin, which is also associated with increased sun sensitivity.
What each genotype means
Typical MC1R function
You carry two copies of the common reference allele at this position, corresponding to intact Arg160 receptor signaling. This genotype is associated with baseline eumelanin production and typical pigmentation patterns for your genetic background. It does not confer the elevated likelihood of red hair, pale skin, or increased sun-associated skin cancer risk linked to the Arg160Trp variant.
Carried by approximately 80% to 90% of people of European descent and nearly 100% of individuals of African and East Asian ancestry.
Carrier of red hair allele
You carry one copy of the Arg160Trp variant allele (often designated a classic 'R' red hair allele) and one reference allele. Research demonstrates that having a single copy can moderately increase your propensity for freckling, sun sensitivity, and lighter pigmentation, though red hair typically requires an additional variant allele in MC1R. Studies also associate carrying one copy with an increased baseline susceptibility to UV-related skin damage and skin cancers relative to non-carriers.
Found in roughly 10% to 18% of individuals of Northern and Western European heritage, while rare to absent in African and East Asian populations.
Strongly altered MC1R signaling
You carry two copies of the Arg160Trp missense variant, significantly reducing MC1R receptor function and shifting pigment synthesis toward reddish-yellow pheomelanin. This genotype is strongly associated with red hair, fair skin that burns easily, prominent freckling, and reduced natural UV photoprotection. Population studies show a considerably higher statistical risk of sun sensitivity and cutaneous melanoma compared to individuals with functional receptor alleles.
Found in approximately 0.5% to 1.5% of people of Northern and Western European descent, and virtually absent in non-European ancestries.
Genetic Location and Molecular Mechanism
The rs1805004 variant sits on chromosome 16 in the coding region of the MC1R gene. It involves a single nucleotide substitution where cytosine (C) is swapped with thymine (T), resulting in an arginine-to-tryptophan amino acid change at position 160 (Arg160Trp, often designated R160W in literature). Under typical conditions, the melanocortin 1 receptor resides on the surface of melanocytes and binds alpha-melanocyte-stimulating hormone (alpha-MSH). This signaling cascade stimulates intracellular cyclic AMP (cAMP) production, initiating the synthesis of dark, UV-protective eumelanin. The Arg160Trp variant impairs receptor cell-surface signaling, significantly reducing downstream cAMP activation and tipping pigment synthesis toward reddish, sulfur-rich pheomelanin instead.
Phenotypic Associations and Evidence Strength
Decades of genomic research classify rs1805004 as one of the major 'R' (high penetrance) alleles associated with the red hair color (RHC) phenotype. Carrying two high-penetrance MC1R alleles—such as being homozygous for rs1805004 or a compound heterozygote with alleles like R151C or D294H—confers a very high likelihood of natural red hair, fair skin, and prominent freckles. Beyond hair color, the epidemiological evidence links this variant to reduced tanning response, greater propensity to sunburn, and a modestly elevated susceptibility to both melanoma and non-melanoma skin cancers. The increased risk arises both from reduced photoprotective eumelanin and potentially UV-independent oxidative stress generated by pheomelanin synthesis.
Population Frequency and Evolutionary Context
The distribution of rs1805004 is strikingly ancestry-dependent. The minor T allele occurs with an allele frequency of approximately 5% to 10% in Northern and Western European populations, reaching its highest frequencies in regions such as the British Isles and parts of Scandinavia. In contrast, the variant is exceptionally rare or absent in populations of East Asian and African ancestry, where evolutionary pressure has historically favored strict maintenance of eumelanin-rich pigmentation for photoprotection near the equator. Researchers hypothesize that relaxed selective constraint or local adaptation for vitamin D synthesis at higher latitudes allowed loss-of-function MC1R variants like rs1805004 to persist and spread in ancient northwestern European lineages.
What You Can and Cannot Conclude
Finding this variant in your genomic profile offers insight into inherited pigmentation traits, but it is not a direct medical diagnosis. Genetic traits like hair color and skin pigmentation are multigenic, meaning other modifier genes also shape final hair shading and freckle density. While rs1805004 correlates statistically with greater sun sensitivity and elevated skin cancer risk, carrying the variant does not guarantee skin cancer will occur, nor does its absence guarantee immunity. This information serves as an educational reminder to practice prudent sun safety—such as using broad-spectrum sunscreen, wearing protective clothing, avoiding tanning beds, and having regular full-body skin checks performed by a dermatologist.
How common is this variant?
The minor T allele has an approximate frequency of 0.05 to 0.10 in Northern and Western European populations, whereas it is virtually absent in unadmixed African and East Asian populations.
Frequently asked questions
Does having the rs1805004 variant guarantee I will have red hair?
No single variant acts entirely on its own. While inheriting two copies of rs1805004 (or one copy alongside another strong MC1R allele) heavily predisposes an individual to red hair, modifier genes can influence the shade, producing strawberry blond, auburn, or light brown hair instead.
Can two parents without red hair have a child with the TT genotype?
Yes, two non-red-haired parents who each carry one copy of the T allele (CT genotype) can pass it on. There is a 25% chance for their biological child to inherit both copies (TT) and display the red hair trait.
Does rs1805004 affect skin cancer risk?
Yes, research indicates that the Arg160Trp change is associated with elevated rates of melanoma and non-melanoma skin cancers. This is largely attributed to reduced protective eumelanin, higher skin sensitivity to UV radiation, and pheomelanin-associated oxidative stress.
Are there differences in pain or anesthesia tolerance linked to this gene?
Several observational studies suggest individuals carrying red-hair-associated MC1R variants may exhibit differences in pain perception and sensitivity to certain anesthetic agents. However, findings remain mixed, and you should always discuss any anesthesia or pain management plans directly with your healthcare team.
Sources & further reading
Educational information only, last refreshed 9/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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