Free for academic non-profit institutions. Other users need a Commercial license

Aliases for MC4R Gene

Aliases for MC4R Gene

  • Melanocortin 4 Receptor 2 3 5
  • MC4-R 3 4
  • Melanocortin Receptor 4 3

External Ids for MC4R Gene

Previous GeneCards Identifiers for MC4R Gene

  • GC18M057869
  • GC18M058011
  • GC18M056187
  • GC18M056189
  • GC18M054747

Summaries for MC4R Gene

Entrez Gene Summary for MC4R 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]

GeneCards Summary for MC4R Gene

MC4R (Melanocortin 4 Receptor) is a Protein Coding gene. Diseases associated with MC4R include Body Mass Index Quantitative Trait Locus 11 and Schizophrenia. Among its related pathways are Signaling by GPCR and Peptide ligand-binding receptors. Gene Ontology (GO) annotations related to this gene include G-protein coupled receptor activity and peptide hormone binding. An important paralog of this gene is MC5R.

UniProtKB/Swiss-Prot for MC4R Gene

  • 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).

Tocris Summary for MC4R Gene

  • Melanocortin receptors are activated by members of the melanocortin family: alpha-, beta- and gamma-melanocyte stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH). The melanocortins are involved in a range of physiological functions, including pigmentation and inflammation.

Gene Wiki entry for MC4R Gene

Additional gene information for MC4R Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MC4R Gene

Genomics for MC4R Gene

GeneHancer (GH) Regulatory Elements for MC4R Gene

Promoters and enhancers for MC4R Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH18J060372 Promoter/Enhancer 0.9 Ensembl ENCODE 650.7 0.0 -17 0.8 POLR2A CHD2 MC4R GC18M060463
GH18J060295 Enhancer 0.3 ENCODE 11.1 +76.9 76882 0.9 MAFK LOC105372155 MC4R
GH18J059389 Enhancer 0.4 ENCODE 5.1 +983.0 982966 0.6 POLR2A ZSCAN4 LMAN1 MC4R ENSG00000267677 GC18M059402
GH18J060446 Enhancer 0.5 FANTOM5 ENCODE 0.2 -74.4 -74417 1.2 POLR2A GC18M060463 MC4R
GH18J060448 Enhancer 0.3 ENCODE 0.2 -75.9 -75898 0.2 SP1 GC18M060463 MC4R
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MC4R on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MC4R gene promoter:
  • CREB
  • deltaCREB
  • POU6F1 (c2)
  • TBP
  • ARP-1
  • POU2F1
  • POU2F1a
  • E47
  • Tal-1beta

Genomic Locations for MC4R Gene

Genomic Locations for MC4R Gene
chr18:60,371,110-60,372,775
(GRCh38/hg38)
Size:
1,666 bases
Orientation:
Minus strand
chr18:58,038,564-58,040,001
(GRCh37/hg19)
Size:
1,438 bases
Orientation:
Minus strand

Genomic View for MC4R Gene

Genes around MC4R on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MC4R Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MC4R Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MC4R Gene

Proteins for MC4R Gene

  • Protein details for MC4R Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P32245-MC4R_HUMAN
    Recommended name:
    Melanocortin receptor 4
    Protein Accession:
    P32245
    Secondary Accessions:
    • B2RAC3
    • Q16317
    • Q3MIJ6

    Protein attributes for MC4R Gene

    Size:
    332 amino acids
    Molecular mass:
    36943 Da
    Quaternary structure:
    • Interacts with ATRNL1 (By similarity). Homodimer; disulfide-linked, also forms higher order oligomers. Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; this interaction competes with GNAS-binding and thus inhibits agonist-induced cAMP production. Interacts with MRAP and MRAP2; these associated factors increase ligand-sensitivity and generation of cAMP.

    Three dimensional structures from OCA and Proteopedia for MC4R Gene

neXtProt entry for MC4R Gene

Post-translational modifications for MC4R Gene

  • Glycosylation at posLast=2626, posLast=1717, and isoforms=3
  • Modification sites at PhosphoSitePlus

Other Protein References for MC4R Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for MC4R Gene

Domains & Families for MC4R Gene

Gene Families for MC4R Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • G-protein coupled receptors
  • Potential drug targets
  • Predicted membrane proteins
  • Transporters

Graphical View of Domain Structure for InterPro Entry

P32245

UniProtKB/Swiss-Prot:

MC4R_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with MC4R: view

Function for MC4R Gene

Molecular function for MC4R Gene

UniProtKB/Swiss-Prot Function:
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).
GENATLAS Biochemistry:
melanocortin receptor 4,expressed in brain,placenta and intestinal tissue,G protein coupled receptor superfamily,involved in energy balance,but likely to be a minor contributor in obesity

Phenotypes From GWAS Catalog for MC4R Gene

Gene Ontology (GO) - Molecular Function for MC4R Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004871 obsolete signal transducer activity IEA --
GO:0004930 G-protein coupled receptor activity IEA --
GO:0004977 melanocortin receptor activity TAS 8794897
GO:0004980 melanocyte-stimulating hormone receptor activity IPI 19743876
GO:0005515 protein binding IPI 19329486
genes like me logo Genes that share ontologies with MC4R: view
genes like me logo Genes that share phenotypes with MC4R: view

Human Phenotype Ontology for MC4R Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MC4R Gene

MGI Knock Outs for MC4R:

Animal Model Products

  • Taconic Biosciences Mouse Models for MC4R

CRISPR Products

miRNA for MC4R Gene

miRTarBase miRNAs that target MC4R

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MC4R

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for MC4R Gene

Localization for MC4R Gene

Subcellular locations from UniProtKB/Swiss-Prot for MC4R Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MC4R gene
Compartment Confidence
plasma membrane 5
nucleus 4
extracellular 1
endoplasmic reticulum 1
lysosome 1

Gene Ontology (GO) - Cellular Components for MC4R Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA,TAS --
genes like me logo Genes that share ontologies with MC4R: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MC4R Gene

Pathways & Interactions for MC4R Gene

genes like me logo Genes that share pathways with MC4R: view

SIGNOR curated interactions for MC4R Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for MC4R Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002024 diet induced thermogenesis IEA --
GO:0006112 energy reserve metabolic process IEA --
GO:0007165 signal transduction IEA --
GO:0007186 G-protein coupled receptor signaling pathway TAS --
GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway TAS 8794897
genes like me logo Genes that share ontologies with MC4R: view

Drugs & Compounds for MC4R Gene

(53) Drugs for MC4R Gene - From: PharmGKB, ClinicalTrials, DGIdb, IUPHAR, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Haloperidol Approved Pharma Antagonist, Pore Blocker Antipsychotic drug 155
Amisulpride Approved, Investigational Pharma Antagonist Dopamine D2/D3 receptor antagonist 0
Aripiprazole Approved, Investigational Pharma Antagonist, Full agonist, Agonist Antipsychotic, High affinity D2 and 5-HT1A receptor partial agonist; also 5-HT2A antagonist 373
Clozapine Approved Pharma Antagonist, Positive, Allosteric regulator, Full agonist, Agonist, Inverse agonist Antipsychotic medication 121
Olanzapine Approved, Investigational Pharma Antagonist, Full agonist, Agonist, Inverse agonist 408

(17) Additional Compounds for MC4R Gene - From: Novoseek, IUPHAR, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
MK-0493
Full agonist, Agonist
NDP-MSH
Full agonist, Agonist
[Nle4,D-Phe7]-alpha-MSH
75921-69-6
Melanocyte-stimulating hormone release inhibiting factor
2002-44-0

(5) Tocris Compounds for MC4R Gene

Compound Action Cas Number
[Nle4,D-Phe7]-alpha-MSH Melanocortin receptor agonist 75921-69-6
alpha-MSH Endogenous melanocortin receptor agonist 581-05-5
Melanocyte-stimulating hormone release inhibiting factor Inhibitor of alpha-MSH release; inhibits opioid effects in vivo 2002-44-0
Melanotan II High affinity melanocortin receptor agonist 121062-08-6
THIQ Potent and selective MC4 receptor agonist 312637-48-2
genes like me logo Genes that share compounds with MC4R: view

Transcripts for MC4R Gene

mRNA/cDNA for MC4R Gene

(1) REFSEQ mRNAs :
(4) Additional mRNA sequences :
(2) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for MC4R Gene

Melanocortin 4 receptor:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MC4R

Alternative Splicing Database (ASD) splice patterns (SP) for MC4R Gene

No ASD Table

Relevant External Links for MC4R Gene

GeneLoc Exon Structure for
MC4R
ECgene alternative splicing isoforms for
MC4R

Expression for MC4R Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MC4R Gene

mRNA differential expression in normal tissues according to GTEx for MC4R Gene

This gene is overexpressed in Brain - Hypothalamus (x11.0), Brain - Caudate (basal ganglia) (x7.1), Brain - Anterior cingulate cortex (BA24) (x5.1), and Brain - Putamen (basal ganglia) (x4.8).

NURSA nuclear receptor signaling pathways regulating expression of MC4R Gene:

MC4R

SOURCE GeneReport for Unigene cluster for MC4R Gene:

Hs.532833

mRNA Expression by UniProt/SwissProt for MC4R Gene:

P32245-MC4R_HUMAN
Tissue specificity: Brain, placental, and gut tissues.

Evidence on tissue expression from TISSUES for MC4R Gene

  • Nervous system(4.6)
  • Adrenal gland(2.1)
  • Blood(2.1)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with MC4R: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for MC4R Gene

Orthologs for MC4R Gene

This gene was present in the common ancestor of chordates.

Orthologs for MC4R Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MC4R 34 33
  • 99.8 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MC4R 34
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MC4R 34 33
  • 89.63 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Mc4r 16 34 33
  • 88.72 (n)
rat
(Rattus norvegicus)
Mammalia Mc4r 33
  • 88.32 (n)
cow
(Bos Taurus)
Mammalia MC4R 34 33
  • 87.01 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MC4R 34
  • 82 (a)
OneToOne
chicken
(Gallus gallus)
Aves MC4R 34 33
  • 80.49 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MC4R 34
  • 86 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mc4r 33
  • 70.9 (n)
zebrafish
(Danio rerio)
Actinopterygii mc4r 34 33
  • 68.34 (n)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 19 (a)
ManyToMany
-- 34
  • 16 (a)
ManyToMany
Species where no ortholog for MC4R was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MC4R Gene

ENSEMBL:
Gene Tree for MC4R (if available)
TreeFam:
Gene Tree for MC4R (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MC4R: view image

Paralogs for MC4R Gene

Paralogs for MC4R Gene

(9) SIMAP similar genes for MC4R Gene using alignment to 10 proteins:

  • MC4R_HUMAN
  • A0N0W6_HUMAN
  • A0N0W7_HUMAN
  • A0N0W8_HUMAN
  • A0N0W9_HUMAN
  • K4MTP3_HUMAN
  • K4MUE5_HUMAN
  • K4MWA3_HUMAN
  • K4MWP7_HUMAN
  • K4N7A9_HUMAN
genes like me logo Genes that share paralogs with MC4R: view

Variants for MC4R Gene

Sequence variations from dbSNP and Humsavar for MC4R Gene

SNP ID Clin Chr 18 pos Variation AA Info Type
rs1057517991 (OBESITY) [MIM:601665], pathogenic, not provided 60,371,539(-) A/G coding_sequence_variant, missense_variant
rs121913557 pathogenic, Obesity, Obesity (OBESITY) [MIM:601665] 60,372,202(-) C/A/T coding_sequence_variant, missense_variant
rs121913558 pathogenic, Obesity, Obesity (OBESITY) [MIM:601665] 60,372,178(-) T/A coding_sequence_variant, missense_variant
rs121913559 pathogenic, Obesity, Obesity (OBESITY) [MIM:601665], Obesity (OBESITY) [MIM:601665] 60,372,045(-) A/C/G coding_sequence_variant, missense_variant
rs121913560 pathogenic, Obesity, Obesity (OBESITY) [MIM:601665] 60,371,842(-) T/C coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for MC4R Gene

Variant ID Type Subtype PubMed ID
nsv458092 CNV loss 19166990
nsv577058 CNV loss 21841781

Variation tolerance for MC4R Gene

Residual Variation Intolerance Score: 44.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.03; 50.18% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MC4R Gene

Human Gene Mutation Database (HGMD)
MC4R
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MC4R

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MC4R Gene

Disorders for MC4R Gene

MalaCards: The human disease database

(13) MalaCards diseases for MC4R Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search MC4R in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MC4R_HUMAN
  • Obesity (OBESITY) [MIM:601665]: 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. {ECO:0000269 PubMed:10199800, ECO:0000269 PubMed:11443223, ECO:0000269 PubMed:11487744, ECO:0000269 PubMed:12588803, ECO:0000269 PubMed:12646665, ECO:0000269 PubMed:14671178, ECO:0000269 PubMed:14764818, ECO:0000269 PubMed:15486053}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for MC4R

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MC4R: view

No data available for Genatlas for MC4R Gene

Publications for MC4R Gene

  1. Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. (PMID: 15486053) Larsen LH … Pedersen O (The Journal of clinical endocrinology and metabolism 2005) 3 4 22 44 58
  2. Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. (PMID: 11487744) Dubern B … Tounian P (The Journal of pediatrics 2001) 3 4 22 44 58
  3. Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children. (PMID: 19889825) Cole SA … Gibbs RA (The American journal of clinical nutrition 2010) 3 22 44 58
  4. Sympathetic function in human carriers of melanocortin-4 receptor gene mutations. (PMID: 20147580) Sayk F … Lehnert H (The Journal of clinical endocrinology and metabolism 2010) 3 22 44 58
  5. Association of functionally significant Melanocortin-4 but not Melanocortin-3 receptor mutations with severe adult obesity in a large North American case-control study. (PMID: 19091795) Calton MA … Vaisse C (Human molecular genetics 2009) 3 22 44 58

Products for MC4R Gene

Sources for MC4R Gene

Content
Loading form....