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FLASH GENE

Symbol

MC4R

contributors: mct - updated : 06-10-2018

HGNC name	melanocortin 4 receptor
HGNC id	6932

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain diencephalon thalamus       brain diencephalon hypothalamus suprachiasmatic nuclei   Homo sapiens   brain forebrain cerebral 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed 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