Summary of MC4R
The Function of MC4R
Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP).
Protein names
Recommended name:
Melanocortin receptor 4Short name:
MC4-R- RS10871777 (MC4R) ??
- RS11872992 (MC4R) ??
- RS12970134 (MC4R) ??
- RS17700633 (MC4R) ??
- RS17782313 (MC4R) ??
- RS2229616 (MC4R) ??
- RS4257308 (MC4R) ??
- RS489693 (MC4R) ??
- RS52804924 (MC4R) ??
- RS6567160 (MC4R) ??
- RS663129 (MC4R) ??
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Top Gene-Substance Interactions
MC4R Interacts with These Diseases
Disease | Score |
Fixes
Exercise, calorie restriction, and portion control may help curb fat buildup from over-eating (R). Sun/UV increases MSH (R) - in humans and horses. The light itself may also increase MSH (R). Nicotine activates the MC4 Receptors (R), which is the main mechanism of action for MSH (R, R2).
Fixes Advanced
The following activate the MC4 Receptor:
- Melanotan II
- MSH Pro2
Substances That Increase MC4R
Substances | Interaction | Organism | Category |
Substances That Decrease MC4R
Substances | Interaction | Organism | Category |
Advanced Summary
MC4R gene codes for a protein called the Melanocortin 4 Receptor, which regulates weight (R). Consistent with a role in body weight regulation, the MC4R is expressed in a number of hypothalamic sites, including the ventromedial, lateral, dorsomedial, and paraventricular nuclei (R).
MC4R responds in part to hormones influenced by alpha-, beta-, and gamma-MSH (melanocyte-stimulating hormone, which is related to the skin pigment, melanin) and other signals from the brain (R).
MC4R is activated by inflammation (R).
MC4R has the same function in humans as in mice, so it is easy to test the genes effects (R).
The mutant version of the MC4R gene produces a protein receptor that doesn't activate as well - it is less sensitive to signals from the body that tell the body that it is already full (R).
The mutant version of MC4R leads to a higher percentage of obesity because the satiated signals that reach the receptor protein cannot effectively tell the person to stop eating (R).
MC4R not working is the most common genetic cause of obesity (R).
Lack of this gene and its associated protein makes mice taller (R).
The mutant MC4R gene (which allows for overeating) was beneficial for early humans, whose food source was scarce and needed the fat buildup. Similarly, creatures like bears still contain the mutant version as they need to store fat during winters (R).
Leptin reduces weight through MC4R (R).
Activating the MC4R induces anxiety, inhibits appetite and activates the HPA axis (R).
Activating MC4R enhances libido (R).
Activating MC4R stimulates the thyroid hormone precursor TRH (precursor to TSH) (R).
MC4R activation increases morphine tolerance (R).
MC4R activation reduces proinflammatory cytokines (such as IL-1, IL-6, and TNF-) and MMP9 and increases the anti-inflammatory cytokine IL-10 (R, R2, R3).
People with chronic stress and/or inflammation will have the MC4R receptor activated, which then leads to flushing, weight loss, lower blood pressure and increased pain (R).
From NCBI Gene: ObesityFrom UniProt: Obesity (OBESITY): A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. [MIM:601665]
From NCBI Gene: The protein encoded by this gene is a membrane-bound receptor and member of the melanocortin receptor family. The encoded protein interacts with adrenocorticotropic and MSH hormones and is mediated by G proteins. This is an intronless gene. Defects in this gene are a cause of autosomal dominant obesity . [provided by RefSeq, Jan 2010] From UniProt: Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP).
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Brain, placental, and gut tissues.
Gene Pathways:
Molecular Function:
- Melanocortin Receptor Activity
- Melanocyte-Stimulating Hormone Receptor Activity
- Neuropeptide Binding
- Peptide Hormone Binding
- Ubiquitin Protein Ligase Binding
Biological Processes:
- Adenylate Cyclase-Modulating G-Protein Coupled Receptor Signaling Pathway
- Diet Induced Thermogenesis
- Energy Reserve Metabolic Process
- Feeding Behavior
- Insulin Secretion
- Negative Regulation Of Feeding Behavior
- Positive Regulation Of Bone Resorption
- Positive Regulation Of Camp Biosynthetic Process
- Regulation Of Grooming Behavior
- Response To Insulin