MC1R rs1805006: Red Hair and Skin Pigmentation Genetics
The genetic variant rs1805006, also known as Asp84Glu (D84E), is a missense single nucleotide polymorphism in the MC1R gene on chromosome 16. It alters the melanocortin 1 receptor, influencing melanin synthesis and predisposing carriers to red hair, fair skin, and freckling. Carrying this variant also correlates with heightened sensitivity to ultraviolet radiation and an associated risk for melanoma and non-melanoma skin cancers.
What each genotype means
Typical pigmentary function
You carry the most common, non-variant alleles for this position. Research suggests your MC1R receptor function is not altered by this specific genetic marker, meaning it does not contribute to the red hair color phenotype or related changes in UV sensitivity associated with the A allele.
Carried by the vast majority of individuals across all global populations.
Single copy variant carrier
You carry one copy of the A allele, also known as D84E. This variant is associated with a reduction in MC1R function, which can influence how your skin and hair produce pigment. While a single copy generally does not cause red hair on its own, it may contribute to a slightly increased sensitivity to UV radiation and a higher likelihood of freckling compared to those with no variant alleles.
Carried by a small minority of the population, predominantly in those of European ancestry; it is considered rare in other populations.
Dual copy variant carrier
You carry two copies of the A allele, also known as D84E. This genotype is classified as a high-penetrance allele, which significantly impairs MC1R receptor function and is strongly associated with red hair, fair skin, and increased sensitivity to UV radiation. Research indicates that this genotype is linked to an increased risk of developing melanoma and other skin cancers; therefore, prioritizing sun-protective measures and regular skin examinations is strongly advised.
This is a rare genotype, occurring primarily within specific European-descended populations.
Genetic Location and Molecular Identity
The single nucleotide polymorphism rs1805006 is situated in the single coding exon of the melanocortin 1 receptor gene, designated MC1R, located on chromosome 16 at band 16q24.3. At the molecular level, this variation represents a base change from the ancestral cytosine (C) nucleotide to an adenine (A) or guanine (G) allele, most commonly cataloged as a C-to-A transversion. This nucleotide shift alters codon 84 of the protein sequence, replacing an aspartic acid residue with glutamic acid, an alteration historically denoted as Asp84Glu or D84E. Because MC1R encodes a seven-transmembrane G-protein coupled receptor critical for skin and hair biology, changing this amino acid alters receptor conformation and signaling capacity.
Biological Mechanism of the MC1R Receptor
The MC1R protein functions as a central switch in specialized cells known as melanocytes, which produce melanin pigments. Under standard physiological conditions, activation of MC1R by alpha-melanocyte-stimulating hormone elevates intracellular cyclic AMP, prompting melanocytes to synthesize eumelanin, a dark brown-to-black pigment that absorbs and scatters ultraviolet radiation. When loss-of-function variants like rs1805006 occur, receptor signaling diminishes. This functional impairment shifts cellular melanin synthesis toward pheomelanin, a reddish-yellow, sulfur-containing pigment that provides minimal protection against ultraviolet light and can generate reactive oxygen species upon sun exposure, elevating oxidative stress in skin tissue.
Clinical and Phenotypic Associations
In human genetic literature, rs1805006 is traditionally classified as an 'R' allele—a designation reserved for variants with strong penetrance for the red hair color phenotype. Genome-wide association studies catalog rs1805006 among key loci influencing red versus brown or black hair, fair complexion, freckling tendency, and sun-burning susceptibility. Because pheomelanin provides inferior shielding against cellular DNA damage caused by solar radiation, clinical databases like ClinVar record rs1805006 under hereditary susceptibility to cutaneous malignant melanoma and non-melanoma skin neoplasms. However, because skin cancer is multifactorial, this variant confers statistical risk rather than an inevitable medical diagnosis.
Population Distribution and Ancestral Patterns
The rs1805006 variant displays substantial divergence across global populations. It is observed primarily in populations of European heritage, particularly those with ancestry traced to northern, western, and central Europe, where minor allele frequencies commonly range between 0.005 and 0.05, and reach up to 0.10 in targeted cohort subsets. Outside of individuals with European lineage, the alternative allele is exceedingly rare or virtually absent in indigenous African, East Asian, and Native American reference cohorts within large sequencing projects like gnomAD. This population distribution mirrors positive selection and drift events that shaped northern European pigmentary adaptation.
Actionable Insights and Preventive Takeaways
Knowing one's rs1805006 genotype provides an understanding of personal pigmentation genetics and UV sensitivity, but it does not represent a diagnostic test. Regardless of whether an individual carries the common ancestral genotype or the variant allele, standard ultraviolet radiation protection remains crucial. Broad-spectrum sunscreen, protective clothing, and routine self-examinations for atypical moles help mitigate skin cancer risk across all skin types. Genetic test results should never replace professional medical evaluations, and any changing or irregular skin lesions should be evaluated promptly by a dermatologist or primary care provider.
How common is this variant?
The rs1805006 variant is predominantly found in populations of European descent, where the minor allele frequency typically ranges from 0.01 to 0.05 (reaching up to 0.10 in selected regional cohorts), while remaining rare or unobserved in East Asian and African ancestries.
Frequently asked questions
Does having the rs1805006 variant guarantee I will have red hair?
No, carrying the rs1805006 variant does not guarantee red hair. Red hair is largely an inherited recessive trait that typically requires two loss-of-function MC1R variants (either homozygous or compound heterozygous), though single-copy carriers often exhibit lighter hair or freckles.
Does rs1805006 cause melanoma?
The rs1805006 variant does not directly cause melanoma, but it is statistically associated with an increased susceptibility. Because the altered receptor leads to more pheomelanin and less protective eumelanin, skin cells have less natural protection against ultraviolet damage, increasing overall cancer risk.
Can people without red hair carry rs1805006?
Yes, many individuals who do not have red hair carry a single copy of rs1805006. As heterozygous carriers, they may have brown or blonde hair while still inheriting related traits such as fair skin, sun sensitivity, or freckling.
How does rs1805006 affect daily sun protection needs?
Carriers of this variant generally burn more easily and tan less readily due to reduced eumelanin synthesis. Dermatologists recommend diligent sun protection for individuals with MC1R variants, including the use of broad-spectrum SPF 30+ sunscreen, UV-blocking hats, and shade.
Sources & further reading
Educational information only, last refreshed 9/6/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs1805006?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in MC1R
The p.Arg163Gln variant in MC1R is associated with red hair, fair skin, and increased melanoma risk.
This missense variant (p.Arg160Trp) is a primary genetic determinant of red hair color, pale skin, and increased freckling in European populations.
This missense variant (p.Arg142His) is a well-established, highly penetrant allele associated with red hair color and fair skin pigmentation.
The Val60Leu missense variant in MC1R is a well-documented factor contributing to the red hair, fair skin, and freckling phenotype.
A rare variant associated with lighter skin pigmentation in specific populations.
Asp294His coding substitution in the MC1R gene associated with red hair, skin sun-sensitivity, and melanoma risk.