MC1R Gene: Melanocortin 1 Receptor
Key regulator of pigmentation and melanoma risk
Gene Information Card
| Symbol | MC1R |
|---|---|
| Full Name | Melanocortin 1 Receptor |
| Gene Type | Protein coding |
| Chromosomal Location | 16q24.3 |
| NCBI Gene ID | 4157 ncbi.nlm.nih.gov/gene/4157 |
| Ensembl ID | ENSG00000258839 |
| UniProt ID | Q01726 |
| OMIM ID | 155555 |
| HGNC ID | 6929 |
| Aliases | MSHR, CMM5, SHEP2 |
Description
The MC1R gene encodes the melanocortin 1 receptor, a G protein-coupled receptor primarily expressed on melanocytes. It binds melanocyte-stimulating hormone (MSH) and regulates eumelanin (black/brown) versus pheomelanin (red/yellow) pigment production. Variants in MC1R are strongly associated with red hair, fair skin, poor tanning response, and increased susceptibility to melanoma and non-melanoma skin cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma, cutaneous malignant, susceptibility to | Loss-of-function MC1R variants reduce eumelanin synthesis and impair DNA repair after UV damage, increasing melanoma risk | OMIM #155600; ClinVar |
| Skin cancer, non-melanoma (basal cell carcinoma, squamous cell carcinoma) | Reduced photoprotection due to pheomelanin dominance and impaired UV response | OMIM; NCBI GeneReviews |
| Red hair color (RHC) phenotype | Specific MC1R variants (e.g., R151C, R160W, D294H) cause loss of receptor function, leading to pheomelanin production | OMIM #266300; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | High |
| Adipose tissue | 3.2 | Low |
| Brain | 1.8 | Low |
| Testis | 2.1 | Low |
| Lung | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Melanocytes (primary) | 45.0 | High expression; key cell type |
| Melanoma cell lines (e.g., A375) | 30.0 | Variable; often downregulated in metastatic lines |
| HEK293 | 0.2 | Very low; used for recombinant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R151C | Missense | ~10-20% in European populations | Loss of function; strongly associated with red hair and melanoma risk |
| R160W | Missense | ~10-15% in European populations | Loss of function; reduced receptor activity |
| D294H | Missense | ~5-10% in European populations | Loss of function; impaired MSH binding |
| V60L | Missense | ~5% in European populations | Partial loss of function; weaker association with red hair |
| R163Q | Missense | ~2-5% in Asian populations | Reduced function; associated with lighter skin |
Mutation functional classification
Loss of Function (LOF)
Most common; variants like R151C, R160W, D294H impair receptor signaling, reducing eumelanin and increasing pheomelanin, leading to fair skin and red hair.
Gain of Function (GOF)
Rare; some variants may increase receptor activity but are not well characterized in MC1R.
Dominant Negative (DN)
Not clearly established for MC1R; most variants act in a recessive or semi-dominant manner.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • melanocyte-stimulating hormone receptor activity |
| • adenylate cyclase-activating G protein-coupled receptor signaling pathway | • pigmentation |
| • melanin biosynthetic process | • response to UV |
Pathways
• Melanogenesis (KEGG: hsa04916)
• cAMP signaling pathway (KEGG: hsa04024)
• GPCR downstream signaling
Protein Summary
The melanocortin 1 receptor (MC1R) is a 317-amino acid G protein-coupled receptor with seven transmembrane domains. Upon binding α-MSH, it activates adenylate cyclase, increasing cAMP levels, which upregulates microphthalmia-associated transcription factor (MITF) and tyrosinase, driving eumelanin synthesis. Loss-of-function mutations shift melanin production to pheomelanin, resulting in red hair, fair skin, and increased melanoma risk.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MC1R Knockout HEK293 Cell Line | EDJ-KQ50434 | Human | 4157 | Details Get a Quote |
| MC1R Knockout HeLa Cell Line | EDJ-KQ53848 | Human | 4157 | Details Get a Quote |
| MC1R Knockout A-549 Cell Line | EDJ-KQ62334 | Human | 4157 | Details Get a Quote |
| MC1R Knockout HCT 116 Cell Line | EDJ-KQ70809 | Human | 4157 | Details Get a Quote |
| MC1R Knockout A-375 Cell Line | EDC07619 | Human | 4157 | Details Get a Quote |
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