MC4R
Chr 18ADARmelanocortin 4 receptor
Also known as: BMIQ20
The melanocortin 4 receptor is a G protein-coupled receptor in the hypothalamus that binds melanocyte-stimulating hormones and ACTH to regulate energy homeostasis by suppressing appetite and food intake. Mutations cause obesity that can follow either autosomal dominant or autosomal recessive inheritance patterns. The gene shows low constraint against loss-of-function variants (pLI 0.0009, LOEUF 1.6), consistent with its association with obesity rather than severe developmental disorders.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MC4R · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Precision Nutrition Technologies for Obesity Management
NOT YET RECRUITINGAssessing Obesity Related Risk Factors in Adult Population: A Genetic and Behavioral Study
ENROLLING BY INVITATIONStudy to Investigate Genetic Causes of Severe Early Childhood Onset Obesity.
RECRUITINGIntensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity
RECRUITINGCardiometabolic Risk of Obese Subjects: Cross-sectional Study
RECRUITINGIntensive Weight Loss Intervention Versus Usual Care for Adults With Obesity
ACTIVE NOT RECRUITINGEfficacy of Semaglutide s.c. Once-weekly on Weight Loss and Management in Adolescents With Monogenic Obesity in Clinical Practice
RECRUITINGExercise to Fight Obesity
RECRUITINGEMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway
ACTIVE NOT RECRUITINGIntensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial
RECRUITINGExternal Resources
Links to major genomics databases and tools