rs1805008
badMag 5.5This is a variant in the MC1R gene that changes a arginine to an tryptophan.
Key Literature Trait Associations
Red Hair Color
The T allele of MC1R rs1805008 (Arg160Trp, R160W) is one of the three strongest known genetic determinants of red hair. It encodes a loss-of-function variant in the melanocortin-1 receptor, shifting melanin synthesis from eumelanin (brown/black) toward phaeomelanin (red/yellow). Individuals who are compound heterozygous or homozygous for high-penetrance MC1R variants including R160W have up to a 96% probability of having pure red hair.
Cutaneous melanoma
The rs1805008 T allele (MC1R R160W) is a well-established risk factor for cutaneous melanoma across multiple large studies. A 2020 Nature Genetics meta-analysis of 36,760 cases and 375,188 controls identified genome-wide significant melanoma susceptibility at the MC1R locus. A 2011 meta-analysis of 20 studies found that RHC variants as a class confer approximately OR=2.44 (95% CI 1.72–3.45) for melanoma, with R160W being one of the canonical high-risk alleles. An earlier 2008 meta-analysis (Raimondi et al., PMID 18366057) confirmed R160W is associated with melanoma, with individual variant ORs in the 1.4–2.5 range. The risk is mediated by reduced DNA repair capacity and impaired pigmentary protection, and is further amplified in individuals with co-occurring CDKN2A mutations or MITF E31...
Sun sensitivity and tanning ability
The rs1805008 T allele strongly predisposes to sun sensitivity and inability to tan, core features of the RHC (red hair color) phenotype. A genome-wide study found genome-wide significant associations between rs1805008-T and tendency to sunburn (p=2×10⁻²²⁵ in UK Biobank). The mechanistic basis is reduced MC1R-driven eumelanin synthesis, which both reduces constitutive pigmentation and impairs the facultative tanning response to UV exposure. Individuals homozygous for R160W and other RHC alleles are essentially unable to tan and are highly susceptible to UV-induced DNA damage. This UV hypersensitivity underlies the elevated skin cancer risk associated with this variant.
Keratinocyte carcinoma
The rs1805008 T allele is significantly associated with increased risk of keratinocyte cancers (basal cell carcinoma and squamous cell carcinoma combined), with OR=1.21 (95% CI 1.18–1.25, p=6×10⁻⁴²) in a large GWAS meta-analysis of 47,742 cases and 634,413 controls. MC1R is one of six pigmentation loci with overlapping associations across melanoma, BCC, and cSCC. The elevated risk is mediated by impaired eumelanin-based UV protection and reduced nucleotide excision repair capacity — non-pigmentary mechanisms that operate independently of skin color per se. MC1R variants have been confirmed as independent skin cancer risk factors even after adjusting for hair and skin color phenotype.
Pain sensitivity and opioid analgesia
MC1R R160W (rs1805008) has been linked to altered pain processing and analgesic response, particularly in women. A landmark 2003 PNAS study found that women carrying two variant MC1R alleles (compound heterozygotes or homozygotes for RHC alleles) exhibited significantly greater analgesic response to the kappa-opioid pentazocine compared to all other groups, suggesting MC1R mediates sex-specific opioid analgesia. A 2024 narrative review found mixed and inconclusive evidence for red hair/MC1R variants and general pain sensitivity, with some studies showing increased sensitivity in red-haired women and others showing no significant differences. A small clinical study (2025, n=92) found MC1R variants predicted local anesthetic duration but not onset. Evidence is preliminary and largely base...
Parkinson's disease
Some evidence suggests MC1R R160W may influence Parkinson's disease (PD) risk, though findings are inconsistent across studies. A 2015 case-control study (n=870 PD, 736 controls) found marginal association with PD for p.R160W (OR=2.10, p=0.009) in a Spanish population. However, a subsequent meta-analysis (Chen et al., 2017) found p.R151C — not p.R160W — was significantly associated with PD risk (OR=1.10, 95% CI 1.00–1.21), while R160W specifically did not reach significance. A 2016 case-control study with meta-analysis (n=2,657) found a non-significant trend for R160W after removing a heterogeneous outlier study (OR=1.11, 95% CI 0.92–1.35). The biological plausibility involves MC1R expression in dopaminergic neurons and shared melanin-related pathways, but the evidence for R160W specifi...
▶GWAS Catalog Trait Associations (8)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (8)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
Skin/hair/eye pigmentation 2, red hair/fair skin; ALBINISM, OCULOCUTANEOUS, TYPE II, MODIFIER OF; Increased analgesia from kappa-opioid receptor agonist, female-specific; not specified; not provided; Melanoma, cutaneous malignant, susceptibility to, 5; Malignant tumor of breast; SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 2
View on ClinVar →▶Research that mentions this SNP (6)
▶Variants at chromosome 20 (ASIP locus) and melanoma riskAssociationN=1,033Maccioni L. et al.(2013)· International Journal of Cancer
This study examined associations between sun-sensitive pigmentary gene variants and serum PSA levels in 1033 older Australian men. Variants in SLC45A2 (rs28777: -19.6%, rs16891982: -17.3%) were associated with lower PSA levels in all men. Variants in MC1R (rs1805007) and ASIP (rs4911414) showed significant interactions with birth region, with higher PSA levels in ANZ-born men carrying the variants. Post-hoc analysis found increased testosterone in MC1R rs1805007 carriers and elevated dihydrotestosterone in ASIP rs1015362 carriers.
▶Technical note: Quantitative measures of iris color using high resolution photographsAssociationN=402Melissa Edwards et al.(2012)· American Journal of Physical Anthropology
This genome-wide association study (GWAS) of pigmentary traits in East Asian populations (N=305 skin, N=342 iris) identifies a genome-wide significant signal for iris color in the OCA2 region, with rs1800414 (His615Arg) explaining 11.9%, 10.4%, and 6% of variation in b*, a*, and L* coordinates respectively. While no genome-wide significant signals were detected for skin pigmentation, rs2373391 in ZNF804B was replicated in independent Chinese samples (p=0.003).
▶Model-based prediction of human hair color using DNA variantsAssociationN=385Wojciech Branicki et al.(2011)· Human Genetics
This study demonstrates that human hair color can be predicted from DNA variants with high accuracy using a multinomial logistic regression model. A subset of 13 genetic markers from 11 genes (MC1R, HERC2, IRF4, TYR, EXOC2, SLC45A2, TYRP1, OCA2, SLC24A4, KITLG, ASIP) predicted hair color categories in Polish Europeans with AUC values of 0.93 for red hair, 0.87 for black hair, 0.82 for brown hair, and 0.81 for blond hair. MC1R variants showed the strongest association with red hair (OR=12.64 for R variants, P=2.5×10⁻¹⁷), while rs12913832 in HERC2 was significantly associated with darker hair colors (OR=3.33 for black, P=4.3×10⁻⁶).
▶The R402Q tyrosinase variant does not cause autosomal recessive ocular albinismReviewOetting WS et al.(2009)· American Journal of Medical Genetics Part A
Genome-wide association studies and comparative genomics have identified major pigmentation loci (SLC24A5, SLC45A2, TYR, OCA2, MC1R, IRF4, TPCN2) showing evidence of strong natural selection in human populations. Light skin variants in Europeans and Asians underwent complete or near-complete selective sweeps, with SLC24A5 rs1426654 and SLC45A2 variants representing independent evolutionary mechanisms. Critical skin-lightening variants arose 11,000-30,000 years ago during human demographic expansion, driven by UV radiation exposure, vitamin D synthesis requirements, and possibly sexual selection.
▶Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in CaucasiansAssociationN=1,673Hongmei Nan et al.(2009)· International Journal of Cancer
Nested case-control study of 1,673 Caucasian women examining 15 SNPs in pigmentation genes. TYR Arg402Gln (rs1126809) and SLC45A2 Phe374Leu (rs16891982) were significantly associated with skin color and tanning ability. ASIP haplotype (rs4911414[T], rs1015362[G]) increased melanoma risk (OR 1.68) and SCC risk (OR 1.54), while TYRP1 rs1408799 and SLC45A2 -1721 C>G (rs13289) showed protective effects against melanoma (OR 0.77, 0.75 respectively). No associations remained significant after Bonferroni correction.
▶Identification of novel functional variants of the melanocortin 1 receptor gene originated from AsiansFunctionalN=995Kazuhiro Nakayama et al.(2006)· Human Genetics
This functional genetics study identified three novel MC1R gene variants with Asian origins: Phe147Δ, Thr157Ile, and Pro159Thr. In vitro cAMP assays demonstrated that these variants showed impaired signaling similar to or more severe than the European red-hair variant Arg151Cys, suggesting functional constraint on MC1R varies geographically, possibly due to UV light adaptation in Eurasian populations.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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