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FLASH GENE
Symbol MC4R contributors: mct - updated : 06-10-2017
HGNC name melanocortin 4 receptor
HGNC id 6932
Corresponding disease
OBS3 severe obesity
Location 18q21.32      Physical location : 58.038.563 - 58.040.001
Synonym name serpentine melanocortin 4 receptor
Synonym symbol(s) MCR4, MGC126851, MGC138197
DNA
TYPE functioning gene
STRUCTURE 1.44 kb     1 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
Map cen - D18S1152 - D18S41 - D18S858 - D18S1144 - D18S849 - MC4R - D18S499 - D18S862 - D18S68 - D18S42 - D18S55 - D18S1113 - D18S483 - D18S537 - D18S477 - qter
Authors Sundaramurthy (98), Cody (99), LDB
Physical map
MGC33608 18q21.31 hypothetical protein MGC33608 SIAT8C 18q21.2 sialyltransferase 8C (alpha2,3Galbeta1,4GlcNAcalpha 2,8-sialyltransferase) ONECUT2 18q21.1-q21.2 one cut domain, family member 2 FECH 18q21.2 ferrochelatase (protoporphyria) NARS 18q21.2-q21.3 asparaginyl-tRNA synthetase ATP8B1 18q21 ATPase, Class I, type 8B, member 1 LOC284288 18q21.31 similar to Ribosomal protein L24-like LOC388476 18 similar to Nonhistone chromosomal protein HMG-14 (High-mobility group nucleosome binding domain 1) NEDD4L 18q21.2 neural precursor cell expressed, developmentally down-regulated 4-like HAK 18q21.31-q21.32 heart alpha-kinase MALT1 18q21 mucosa associated lymphoid tissue lymphoma translocation gene 1 FLJ10697 LOC390858 18 similar to RIKEN cDNA 5330437I02 gene LOC388477 18 LOC388477 LOC90701 18q21.32 similar to signal peptidase complex (18kD) GRP 18q21.31 gastrin-releasing peptide RAX 18q21.31 retina and anterior neural fold homeobox CPLX4 18q21.32 complexin 4 LMAN1 18q21.3-q22 lectin, mannose-binding, 1 FLJ30681 18q21.32 KIAA1983 protein LOC219542 18q21.32 similar to 40S ribosomal protein S26 LOC390859 18 similar to Chain A, Crystal Structure Of The R463a Mutant Of Human Glutamate Dehydrogenase LOC390860 18 similar to 60S acidic ribosomal protein P0 (L10E) PMAIP1 18q21.32 phorbol-12-myristate-13-acetate-induced protein 1 LOC147072 18q21.32 similar to nuclear factor (erythroid-derived 2)-like 3; NF-E2-related factor 3 LOC388478 18 similar to serologically defined colon cancer antigen 3 LOC284289 18q21.32 similar to TERA protein LOC388479 18 similar to 40S ribosomal protein S3a LOC342784 18q21.32 similar to TFIIH basal transcription factor complex p62 subunit (Basic transcription factor 62 kDa subunit) (BTF2-p62) (General transcription factor IIH polypeptide 1) MC4R 18q21.32 melanocortin 4 receptor MRPS5P4 18q21 mitochondrial ribosomal protein S5 pseudogene LOC220147 18q21.32 similar to C-terminal binding protein 2 isoform 2; ribeye CDH20 18q22-q23 cadherin 20, type 2 LOC388480 18 LOC388480 RNF152 18q21.33 ring finger protein 152 PIGN 18q21.32 phosphatidylinositol glycan, class N KIAA1468 18q21.33 KIAA1468 TNFRSF11A 18q21.3-q22.1 tumor necrosis factor receptor superfamily, member 11a, activator of NFKB LOC390861 18 similar to FKSG30 ZCCHC2 18q21.32 zinc finger, CCHC domain containing 2 PLEKHE1 18q21.32 pleckstrin homology domain containing, family E (with leucine rich repeats) member 1 BCL2 18q21.33 B-cell CLL/lymphoma 2 FVT1 18q21 follicular lymphoma variant translocation 1 VPS4B 18q21.32-q21.33 vacuolar protein sorting 4B (yeast)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
1 - 1438 - 332 - Mountjoy (1994)
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
    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)
  • 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