Spectrum of Phenotypes Associated with Human MC1R Variations

• Razeen Tariq

  Centre for Applied Molecular Biology, University of the Punjab, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0009-0001-4387-0669

• Seher

  Centre for Applied Molecular Biology, University of the Punjab, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0009-0000-3324-013X

• Warda Safdar

  Centre for Applied Molecular Biology, University of the Punjab, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0009-0001-4168-4889

• Haleema Zaheer

  Centre for Applied Molecular Biology, University of the Punjab, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0009-0001-8775-7019

• Aiman Yousuf

  Centre for Applied Molecular Biology, University of the Punjab, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0009-0006-4457-8578

• Arshad Ali

  Centre for Applied Molecular Biology, University of the Punjab, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0009-0008-3265-1648

The melanocortin 1 receptor (MC1R) gene is one of the most important genes involved in human pigmentation, influencing skin, eye and hair colour. It is a G protein-coupled receptor that regulates the production of pheomelanin and eumelanin via activation through α-melanocyte-stimulating hormone (α-MSH) that triggers Cyclic Adenosine Monophosphate cAMP pathway. It causes susceptibility to many dermatological conditions such as albinism and melanoma. Different variants of the MC1R are responsible for different phenotypes such as blue-green eyes, light skin, red hair and increased sensitivity to UV light. Red hair colour (RHC) variants including p.V60L, p.D84E, p.V92M p.R142H, p.R151C,  found in fair skin type, red hair and in albinos and melanoma. Although less common, other variants have also been reported. MC1R variants also contribute to altered DNA repair mechanism and increase melanoma risk. MC1R is a key genetic marker in forensic investigations, primarily used for phenotypic prediction, such as determining hair and skin color. Variants in the MC1R are associated with red hair, fair skin, and increased freckling, which can help narrow down suspect profiles. This review explores the molecular mechanism of MC1R function, signaling pathway and phenotypic spectrum associated with its genetic variants. 

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