oculocutaneous albinism Certain genetic changes in the MC1R gene modify the appearance of people with oculocutaneous albinism type 2. This form of albinism, which is caused by mutations in the OCA2 gene, is characterized by fair hair, light-colored eyes, creamy white skin, and vision problems. People with genetic changes in both the OCA2 and MC1R genes have many of the usual features of oculocutaneous albinism type 2; however, they typically have red hair instead of the usual yellow, blond, or light brown hair seen with this condition. cancers Many genetic changes in the MC1R gene increase the risk of developing skin cancer, including a common, serious form of skin cancer that begins in melanocytes (melanoma). Alterations in the MC1R gene disrupt the ability of the melanocortin 1 receptor to trigger eumelanin production in melanocytes. Because eumelanin normally protects skin from the harmful effects of UV radiation, a lack of this pigment leaves fair skin more vulnerable to damage from sun exposure. Skin damage caused by UV radiation from the sun is a major risk factor for developing melanoma and other forms of skin cancer. Studies suggest that variations in the MC1R gene may also increase the risk of developing melanoma in the absence of UV radiation-related skin damage. In these cases, melanomas can occur in people of dark or light skin coloring. These cancers are often associated with mutations in additional genes related to melanoma risk, such as the BRAF and CDKN2A genes. Researchers are working to explain the complex relationship among MC1R variations, other genetic and environmental factors, and melanoma risk.

     The MC1R gene provides instructions for making a protein called the melanocortin 1 receptor. This receptor plays an important role in normal pigmentation. The receptor is primarily located on the surface of melanocytes, which are specialized cells that produce a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. Melanin is also found in the light-sensitive tissue at the back of the eye (the retina), where it plays a role in normal vision. Melanocytes make two forms of melanin, eumelanin and pheomelanin. The relative amounts of these two pigments help determine the color of a person's hair and skin. People who produce mostly eumelanin tend to have brown or black hair and dark skin that tans easily. Eumelanin also protects skin from damage caused by ultraviolet (UV) radiation in sunlight. People who produce mostly pheomelanin tend to have red or blond hair, freckles, and light-colored skin that tans poorly. Because pheomelanin does not protect skin from UV radiation, people with more pheomelanin have an increased risk of skin damage caused by sun exposure. The melanocortin 1 receptor controls which type of melanin is produced by melanocytes. When the receptor is activated, it triggers a series of chemical reactions inside melanocytes that stimulate these cells to make eumelanin. If the receptor is not activated or is blocked, melanocytes make pheomelanin instead of eumelanin. Common variations (polymorphisms) in the MC1R gene are associated with normal differences in skin and hair color. Certain genetic variations are most common in people with red hair, fair skin, freckles, and an increased sensitivity to sun exposure. These MC1R polymorphisms reduce the ability of the melanocortin 1 receptor to stimulate eumelanin production, causing melanocytes to make mostly pheomelanin. Although MC1R is a key gene in normal human pigmentation, researchers believe that the effects of other genes also contribute to a person's hair and skin coloring. The melanocortin 1 receptor is also active in cells other than melanocytes, including cells involved in the body's immune and inflammatory responses. The receptor's function in these cells is unknown.

The following transcription factors affect gene expression:

• NF-kappaB
• NF-kappaB1
• USF1
• USF-1

Tissue specificity:

Melanocytes and corticoadrenal tissue.

Molecular Function:

• Melanocortin Receptor Activity
• Melanocyte-Stimulating Hormone Receptor Activity
• G-Protein Coupled Peptide Receptor Activity
• Ubiquitin Protein Ligase Binding

Biological Processes:

• G-Protein Coupled Receptor Signaling Pathway, Coupled To Cyclic Nucleotide Second Messenger
• Multicellular Organism Development
• Uv Protection
• Positive Regulation Of Protein Kinase A Signaling
• Sensory Perception Of Pain
• Positive Regulation Of Camp Biosynthetic Process
• Negative Regulation Of Tumor Necrosis Factor Production
• Intracellular Signal Transduction
• Melanin Biosynthetic Process
• Pigmentation
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Positive Regulation Of Protein Kinase B Signaling
• Uv-Damage Excision Repair
• Positive Regulation Of Protein Kinase C Signaling