Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Melanocortin receptor 4

The MC4R gene encodes a G-coupled melanocortin receptor that also binds ACTH. Mutations cause autosomal dominant obesity.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Research Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 25 days
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Autosomal dominant obesity
MC4R

References:

1.

Magenis RE et. al. (1994) Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human.

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2.

Gantz I et. al. (1993) Molecular cloning, expression, and gene localization of a fourth melanocortin receptor.

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3.

Huszar D et. al. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice.

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4.

Sundaramurthy D et. al. (1998) Assignment of the melanocortin 4 receptor (MC4R) gene to human chromosome band 18q22 by in situ hybridisation and radiation hybrid mapping.

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5.

Yeo GS et. al. (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity.

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6.

Vaisse C et. al. (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity.

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7.

Marsh DJ et. al. (1999) Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides.

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8.

Hinney A et. al. (1999) Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans.

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9.

Sina M et. al. (1999) Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene.

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10.

Cody JD et. al. (1999) Haplosufficiency of the melancortin-4 receptor gene in individuals with deletions of 18q.

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11.

Kim KS et. al. (2000) A missense variant of the porcine melanocortin-4 receptor (MC4R) gene is associated with fatness, growth, and feed intake traits.

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12.

Cummings DE et. al. (2000) Melanocortins and body weight: a tale of two receptors.

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13.

Chen AS et. al. (2000) Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass.

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14.

Ste Marie L et. al. (2000) A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors.

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15.

Mergen M et. al. (2001) A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid obesity.

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16.

Dubern B et. al. (2001) Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children.

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17.

Brocke KS et. al. (2002) The human intronless melanocortin 4-receptor gene is NMD insensitive.

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18.

Heisler LK et. al. (2002) Activation of central melanocortin pathways by fenfluramine.

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19.

Van der Ploeg LH et. al. (2002) A role for the melanocortin 4 receptor in sexual function.

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20.

Jacobson P et. al. (2002) Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort.

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21.

Lubrano-Berthelier C et. al. (2003) Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations.

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22.

Yeo GS et. al. (2003) Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms.

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23.

Farooqi IS et. al. (2003) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene.

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24.

Branson R et. al. (2003) Binge eating as a major phenotype of melanocortin 4 receptor gene mutations.

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25.

List JF et. al. (2003) Defective melanocortin 4 receptors in hyperphagia and morbid obesity.

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26.

Nijenhuis WA et. al. (2003) Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity.

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27.

Xu B et. al. (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor.

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28.

Hinney A et. al. (2003) Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity.

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29.

Donohoue PA et. al. (2003) Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female.

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30.

Santini F et. al. (2004) Genetic screening for melanocortin-4 receptor mutations in a cohort of Italian obese patients: description and functional characterization of a novel mutation.

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31.

Valli-Jaakola K et. al. (2004) Identification and characterization of melanocortin-4 receptor gene mutations in morbidly obese finnish children and adults.

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32.

Hebebrand J et. al. (2004) Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations.

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33.

Lubrano-Berthelier C et. al. (2004) A homozygous null mutation delineates the role of the melanocortin-4 receptor in humans.

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34.

Larsen LH et. al. (2005) Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity.

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35.

Tao YX et. al. (2005) Functional analyses of melanocortin-4 receptor mutations identified from patients with binge eating disorder and nonobese or obese subjects.

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36.

Balthasar N et. al. (2005) Divergence of melanocortin pathways in the control of food intake and energy expenditure.

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37.

Hinney A et. al. (2006) Prevalence, spectrum, and functional characterization of melanocortin-4 receptor gene mutations in a representative population-based sample and obese adults from Germany.

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38.

Lubrano-Berthelier C et. al. (2006) Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating.

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39.

Hainerová I et. al. (2007) Melanocortin 4 receptor mutations in obese Czech children: studies of prevalence, phenotype development, weight reduction response, and functional analysis.

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40.

Chambers JC et. al. (2008) Common genetic variation near MC4R is associated with waist circumference and insulin resistance.

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41.

Loos RJ et. al. (2008) Common variants near MC4R are associated with fat mass, weight and risk of obesity.

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42.

Willer CJ et. al. (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.

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43.

Hardy R et. al. (2010) Life course variations in the associations between FTO and MC4R gene variants and body size.

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44.

Mineur YS et. al. (2011) Nicotine decreases food intake through activation of POMC neurons.

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45.

Lim BK et. al. (2012) Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens.

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46.

Ghamari-Langroudi M et. al. (2015) G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons.

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Update: Sept. 26, 2018