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FLASH GENE
Symbol MC4R contributors: mct - updated : 06-10-2018
HGNC name melanocortin 4 receptor
HGNC id 6932
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbraindiencephalonthalamus  
 braindiencephalonhypothalamussuprachiasmatic nuclei  Homo sapiens
 brainforebraincerebral cortex  
 spinal cord    
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text pregnancy
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven transmembrane segments (7TM) receptor, and TM6 has pleiotropic functions
  • a third intracellular loop being essential for the functional activity but also for the regulation and maintenance of an optimal constitutive activity of MC4R in association with G protein coupling, in the control of energy homeostasis
  • HOMOLOGY
    Homologene
    FAMILY
  • G-protein coupled receptor 1 family
  • CATEGORY signaling hormone , receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,nucleus
    basic FUNCTION
  • playing a central role in the control of energy homeostasis and in the regulation of the body weight
  • playing a role in the central control of pituitary function (Mountjoy 1994)
  • role for MC4R expressed in cholinergic neurons in the regulation of insulin levels and in the development of obesity-induced hypertension
  • MC4R in POMC neurons are important for regulation of energy balance
  • is a G protein-coupled receptor involved in food intake and energy expenditure regulation
  • essential role for Ca(2+) signaling in the MC4R pathway that leads to satiety, and a non-redundant role for SLC24A4-mediated Ca(2+) extrusionrusion in controlling MC4R signaling and feeding behavior
  • is a critical coordinator of mammalian energy homeostasis and body weight
  • intact melanocortin signaling via the G protein-coupled receptors (GPCRs), MC4R and MC3R is crucial for body weight maintenance
  • plays a pivotal role in the regulation of body fat and food and energy intake
  • MC4R expression levels in in peripheral blood cells are related with body fat distribution and percentage of energy intake from carbohydrates and fat
  • MC4R is implicated in the central control of sexual function
  • neural melanocortin receptors (MCRs), MC3R and MC4R, play crucial roles in the regulation of energy homeostasis
  • melanocortin 4 receptor (MC4R) is implicated in the central control of sexual function
  • melanocortin signaling via the MC4R on SIM1 neurons implicated in the central control of male sexual behavior
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal
    a component
  • complex MC4R-MRAP2 throws light on the action of ACTH and, by extension, on the relay of stress-related information to additional biological systems
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NHLH2 is a transcriptional regulator of MC4R
  • specifically inhibited the presynaptic N-type channel subtype, and this inhibition may be important for the effects of melanocortin in the central subdivision of the amygdala
  • link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (MC4R)
  • MRAP2 interaction with the melanocortin-4-receptor (MC4R) affects receptor signaling
  • RNF11 inhibits MC3R, MC4R signaling
  • coupling of MC4R to KCNJ13 may explain unusual aspects of the control of energy homeostasis by melanocortin signalling, including the gene dosage effect of MC4R and the sustained effects of AGRP on food intake
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) OBS3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    results in hyperphagia, obesity and increased growth
    Susceptibility
  • to obesity (major contributor)(Hotta 2009)
  • to infantile spasms
  • to Polycystic ovary syndrome (PCOS)
  • Variant & Polymorphism SNP , other
  • rs17782313 associate with fat mass, weight and height, suggesting an overall influence on adult size as well as an increased risk of obesity (Thorleifsson, Hotta 2009)
  • genetic variants in the MC4R promoter are associated with the development of infantile spasms, and rs11872992 polymorphism influences ACTH treatment responses in patients with infantile spasms (Liu 2007)
  • interaction between common variants of FTO and MC4R is associated with risk of PCOS
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    obesity  
    therapy including partial agonists of the MC4R could normalize the appetite and inhibit compulsive eating
    ANIMAL & CELL MODELS
  • hyperphagia following germline loss of MC4R in male mice promotes growth while suppressing the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis