MC4R (Melanocortin receptor 4) variants and mutations

MC4R (also known as Melanocortin receptor 4) is a human protein-coding gene encoding a melanocortin receptor 4 protein. Its melanocortin signaling in hypothalamic circuits suppresses appetite and helps regulate energy expenditure and body weight. Loss-of-function variants are the most common known cause of monogenic obesity and typically produce early hyperphagia. This analysis covers 850 MC4R variants and mutations. Of these, 89% have computational variant effect predictions. Disease context includes obesity disorder, Obesity, and Abnormality of the skeletal system. Example MC4R variants include V2A, N3K, and N3S.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable MC4R variants

Examples include V2A, N3K, N3S, S4A, S4F, S4Y, S4S, S4C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.