MC4R Gene: Melanocortin 4 Receptor
Key regulator of energy homeostasis and body weight; mutations cause monogenic obesity
Gene Information Card
| Symbol | MC4R |
|---|---|
| Full Name | Melanocortin 4 receptor |
| Gene Type | protein coding |
| Chromosomal Location | 18q21.32 |
| NCBI Gene ID | 4160 ncbi.nlm.nih.gov/gene/4160 |
| Ensembl ID | ENSG00000166603 |
| UniProt ID | P32245 |
| OMIM ID | 155541 |
| HGNC ID | 6932 |
| Aliases | MGC126851; MGC138196 |
Description
The MC4R gene encodes the melanocortin 4 receptor, a G-protein coupled receptor (GPCR) that is primarily expressed in the brain, particularly in the hypothalamus. It is a critical component of the leptin-melanocortin pathway, regulating energy homeostasis, food intake, and body weight. Activation of MC4R by alpha-melanocyte-stimulating hormone (α-MSH) leads to reduced food intake and increased energy expenditure. Loss-of-function mutations in MC4R are the most common monogenic cause of severe early-onset obesity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | Loss-of-function mutations impair receptor signaling, leading to hyperphagia and reduced energy expenditure. | ClinVar; OMIM 155541; PMID: 10903341 |
| Binge eating disorder | MC4R variants are associated with increased risk of binge eating behavior. | ClinVar; PMID: 23385548 |
| Hyperinsulinemia | MC4R dysfunction may contribute to insulin resistance and hyperinsulinemia independent of obesity. | PMID: 18782851 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 0.0 | Not detected (protein is expressed in specific brain regions, not whole tissue) |
| Hypothalamus | Not available | High expression (protein level) |
| Adipose tissue | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 0.0 | Low/undetectable in standard RNA-seq; protein may be present in neuronal cells |
| HEK293 | 0.0 | Not endogenously expressed; used for recombinant expression studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| V103I (rs2229616) | Missense | ~2-5% in general population | Reduced function; associated with increased obesity risk |
| I251L (rs52820871) | Missense | ~2% in general population | Gain-of-function; protective against obesity |
| S127L | Missense | Rare | Loss-of-function; causes severe obesity |
| R165W | Missense | Rare | Loss-of-function; causes severe obesity |
| N62S | Missense | Rare | Loss-of-function; causes severe obesity |
Mutation functional classification
Loss of Function (LOF)
Most MC4R mutations causing obesity are loss-of-function, impairing receptor trafficking, ligand binding, or G-protein coupling, leading to reduced cAMP signaling.
Gain of Function (GOF)
Rare gain-of-function mutations (e.g., I251L) enhance receptor signaling and are associated with reduced obesity risk.
Dominant Negative (DN)
Some MC4R mutations may exert dominant-negative effects by heterodimerizing with wild-type receptors, reducing overall signaling.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • melanocyte-stimulating hormone receptor activity |
| • peptide hormone binding | • plasma membrane |
| • integral component of plasma membrane | • adenylate cyclase-activating G protein-coupled receptor signaling pathway |
| • positive regulation of cAMP-mediated signaling | • feeding behavior |
| • energy homeostasis | • response to leptin |
Pathways
• Leptin-melanocortin pathway
• GPCR downstream signaling (cAMP/PKA)
• Regulation of appetite and energy expenditure
Protein Summary
The melanocortin 4 receptor (MC4R) is a 332-amino acid G-protein coupled receptor with seven transmembrane domains. It is predominantly expressed in the central nervous system, especially in the hypothalamus, where it mediates the effects of melanocortins (α-MSH and ACTH) and agouti-related peptide (AgRP). Upon activation, MC4R couples to Gs proteins, stimulating adenylate cyclase and increasing intracellular cAMP levels. This signaling cascade regulates appetite, energy expenditure, and body weight. MC4R is a key drug target for obesity treatment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MC4R Knockout HEK293 Cell Line | EDJ-KQ4413 | Human | 4160 | Details Get a Quote |
| MC4R Knockout HeLa Cell Line | EDJ-KQ53851 | Human | 4160 | Details Get a Quote |
| MC4R Knockout A-549 Cell Line | EDJ-KQ62337 | Human | 4160 | Details Get a Quote |
| MC4R Knockout HCT 116 Cell Line | EDJ-KQ70812 | Human | 4160 | Details Get a Quote |
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