rs1805007 — MC1R Arg151Cys
Risk factor / Drug response · ~8% Northern Europeans
rs1805007 is the strongest MC1R red hair variant. Beyond pigmentation, it significantly affects anesthetic requirements (redheads need ~20% more anesthesia) and melanoma risk independent of UV exposure.
Molecular Mechanism
The Arg151Cys substitution impairs melanocortin-1 receptor signaling, shifting melanin production from eumelanin to pheomelanin. The receptor dysfunction also affects pain perception pathways and DNA repair in melanocytes, explaining the anesthesia and cancer phenotypes.
Peptide Therapeutic Relevance
Alpha-MSH analogs and MC1R-targeting peptides are being developed for photoprotection and melanoma prevention. PepFold generates candidates targeting the MC1R receptor with genotype-specific binding optimization.
Gene: MC1R (Melanocortin 1 Receptor)
Controls eumelanin vs pheomelanin synthesis ratio in melanocytes. Also affects pain perception, inflammation, and DNA repair capacity independent of pigmentation.
Chromosome 16q24.3
Condition: Melanoma Genetic Risk (MC1R)
MC1R variants, particularly rs1805007 (Arg151Cys), increase melanoma risk 2-4 fold independent of UV exposure by impairing DNA repair in melanocytes. Also affects anesthesia requirements.
Prevalence: ~330,000 new melanoma cases/year worldwide; MC1R RHC variants in ~20% of Northern Europeans
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