MC3R (melanocortin 3 receptor)

Gene

• Entrez ID: 4159
• Gene name: Melanocortin 3 receptor
• Gene symbol: MC3R
• Synonyms (NCBI Gene): BMIQ9, MC3, MC3-R, OB20, OQTL
• Chromosome: 20
• Chromosome location: 20q13.2
• Summary: This gene encodes a G-protein-coupled receptor for melanocyte-stimulating hormone and adrenocorticotropic hormone that is expressed in tissues other than the adrenal cortex and melanocytes. This gene maps to the same region as the locus for benign neonata

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74315393	T>A	Risk-factor	Coding sequence variant, missense variant
rs121913556	T>C,G	Risk-factor	Coding sequence variant, missense variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002027	Process	Regulation of heart rate	IEA
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004977	Function	Melanocortin receptor activity	IEA
GO:0004977	Function	Melanocortin receptor activity	TAS	8175743
GO:0004980	Function	Melanocyte-stimulating hormone receptor activity	IBA
GO:0004980	Function	Melanocyte-stimulating hormone receptor activity	IEA
GO:0004980	Function	Melanocyte-stimulating hormone receptor activity	IPI	19743876
GO:0005515	Function	Protein binding	IPI	19329486, 19743876
GO:0005737	Component	Cytoplasm	IBA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	8463333
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007187	Process	G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS	8175743
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IEA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA	19329486, 19743876
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	TAS	8175743
GO:0008217	Process	Regulation of blood pressure	IEA
GO:0016020	Component	Membrane	IEA
GO:0017046	Function	Peptide hormone binding	IBA
GO:0017046	Function	Peptide hormone binding	IEA
GO:0032922	Process	Circadian regulation of gene expression	IEA
GO:0032922	Process	Circadian regulation of gene expression	ISS
GO:0042309	Process	Homoiothermy	IEA
GO:0042923	Function	Neuropeptide binding	IMP	15927146
GO:0045475	Process	Locomotor rhythm	IEA
GO:0048511	Process	Rhythmic process	IEA
GO:0055078	Process	Sodium ion homeostasis	IEA
GO:0060259	Process	Regulation of feeding behavior	IEA

Other IDs

• MIM: 155540
• HGNC: 6931
• e!Ensembl: ENSG00000124089

Protein

• UniProt ID: P41968
• Protein name: Melanocortin receptor 3 (MC3-R)
• Protein function: Receptor for MSH (alpha, beta and gamma) and ACTH. This receptor is mediated by G proteins which activate adenylate cyclase. Required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availabi
• PDB: 8IOC, 8KIG
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	55 → 299	7 transmembrane receptor (rhodopsin family)	Family

• Tissue specificity: TISSUE SPECIFICITY: Brain, placental, and gut tissues.
• Sequence:

  MNASCCLPSVQPTLPNGSEHLQAPFFSNQSSSAFCEQVFIKPEVFLSLGIVSLLENILVI
  LAVVRNGNLHSPMYFFLCSLAVADMLVSVSNALETIMIAIVHSDYLTFEDQFIQHMDNIF
  DSMICISLVASICNLLAIAVDRYVTIFYALRYHSIMTVRKALTLIVAIWVCCGVCGVVFI
  VYSESKMVIVCLITMFFAMMLLMGTLYVHMFLFARLHVKRIAALPPADGVAPQQHSCMKG
  AVTITILLGVFIFCWAPFFLHLVLIITCPTNPYCICYTAHFNTYLVLIMCNSVIDPLIYA
  FRSLELRNTFREILCGCNGMNLG

• Sequence length: 323

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Hormone signaling

Reactome:

Peptide ligand-binding receptors
G alpha (s) signalling events
ADORA2B mediated anti-inflammatory cytokines production

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 9	—	CTD CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MC3R-related disorder	Benign; Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Likely benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
OBESITY (BMIQ9), SUSCEPTIBILITY TO	risk factor	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anorexia	Anorexia	BEFREE	29363944		★☆☆☆☆ Found in Text Mining only
Anorexia Nervosa	Anorexia	LHGDN	16314751		★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	28426141	Associate	★☆☆☆☆ Found in Text Mining only
Benign neonatal epilepsy	Benign Epilepsy	BEFREE	7949735		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	11242591		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	18180070		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	11397906, 12161058		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	11397906, 12161058		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	37070693	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	35955479	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	11397906, 12161058, 18551113		★☆☆☆☆ Found in Text Mining only
Familial benign neonatal epilepsy	Benign Epilepsy	BEFREE	7949735		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	37369769	Associate	★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	BEFREE	10973258, 15636422		★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	Pubtator	22079958	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	24487982		★☆☆☆☆ Found in Text Mining only
Hypoadiponectinemia	Hypoadiponectinemia	BEFREE	18070757		★☆☆☆☆ Found in Text Mining only
Insulin Resistance	Diabetes mellitus, type 2	Pubtator	16123355	Associate	★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral Disc Degeneration	BEFREE	29572167		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	31013889		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	18180070, 23817596		★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Obesity due to MC3R deficiency	Obesity	Orphanet			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	11889220, 12161058, 14506902, 15636422, 17639020, 18231126, 18551113, 19091795, 19656839, 20539302, 20972733, 21047972, 21695122, 22884546, 23280863, 23680515, 24081230, 24142065, 26663875, 26782456, 26818770, 26909893, 27288827, 28073065, 28363697, 29478099, 31090190		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Obesity	Obesity	Pubtator	15276649, 16123355, 17413091, 17639020, 17964765, 18551113, 18614155, 19091795, 19656839, 20539302, 21368909, 22884546, 24081230, 24142065, 25798062, 26663875, 26782456, 27421018, 30926952, 30937899, 33621651, 35026759, 35574020, 37070693, 37329217, 37369769, 39457458	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Obesity	Obesity	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Obesity Morbid	Obesity	Pubtator	33621651	Associate	★☆☆☆☆ Found in Text Mining only
Obesity, Morbid	Obesity	BEFREE	19091795		★☆☆☆☆ Found in Text Mining only
Pediatric Obesity	Childhood obesity	BEFREE	17192297, 17413091, 17639020, 20144537, 21695122, 21983807, 26909893, 29678289, 29688747, 31090190		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	30784330		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	30784330	Associate	★☆☆☆☆ Found in Text Mining only
Synovitis	Synovitis	BEFREE	27853832		★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	38057752	Associate	★☆☆☆☆ Found in Text Mining only