MC4R (melanocortin 4 receptor)

Gene

• Entrez ID: 4160
• Gene name: Melanocortin 4 receptor
• Gene symbol: MC4R
• Synonyms: BMIQ20
• Chromosome: 18
• Chromosome location: 18q21.32
• Summary: 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 thi

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs13447324	G>T	Pathogenic, uncertain-significance	Stop gained, coding sequence variant
rs13447325	T>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs13447331	G>A	Conflicting-interpretations-of-pathogenicity, pathogenic	Coding sequence variant, missense variant
rs13447339	TC>-	Pathogenic	Coding sequence variant, frameshift variant
rs52804924	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs79783591	A>T	Pathogenic, uncertain-significance, benign	Coding sequence variant, missense variant
rs121913557	C>A,T	Pathogenic	Missense variant, coding sequence variant
rs121913558	T>A	Pathogenic	Missense variant, coding sequence variant
rs121913559	A>C,G	Pathogenic	Missense variant, coding sequence variant
rs121913560	T>C	Pathogenic	Missense variant, coding sequence variant
rs121913561	T>C	Pathogenic	Missense variant, coding sequence variant
rs121913562	C>A,T	Pathogenic	Missense variant, coding sequence variant
rs121913563	C>T	Pathogenic	Missense variant, coding sequence variant
rs121913564	A>C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs121913565	T>C	Pathogenic	Missense variant, coding sequence variant
rs121913566	T>C	Pathogenic	Missense variant, coding sequence variant
rs121913567	G>A	Pathogenic	Missense variant, coding sequence variant
rs121917829	A>T	Pathogenic	Stop gained, coding sequence variant
rs187152753	C>T	Pathogenic	Missense variant, coding sequence variant
rs193922685	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs193922687	CA>-,CACA	Pathogenic	Frameshift variant, coding sequence variant
rs369841551	G>A,T	Pathogenic	Stop gained, coding sequence variant, missense variant
rs370479598	C>T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs376439188	A>G	Pathogenic	Missense variant, coding sequence variant
rs549442687	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs747681609	C>T	Pathogenic	Coding sequence variant, missense variant
rs751160202	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs751914635	A>T	Pathogenic	Stop gained, coding sequence variant
rs756232889	A>G	Pathogenic	Coding sequence variant, missense variant
rs766665118	G>A	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs770293321	GT>-	Pathogenic	Inframe indel, stop gained, coding sequence variant
rs772213710	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs772393451	A>T	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs942758928	C>T	Pathogenic	Missense variant, coding sequence variant
rs1057517991	A>G	Pathogenic	Missense variant, coding sequence variant
rs1555691353	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs1555691402	G>A	Pathogenic, uncertain-significance	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT037223	hsa-miR-877-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002024	Process	Diet induced thermogenesis	IEA
GO:0004930	Function	G protein-coupled receptor activity	IBA	21873635
GO:0004977	Function	Melanocortin receptor activity	TAS	8794897
GO:0004980	Function	Melanocyte-stimulating hormone receptor activity	IBA	21873635
GO:0004980	Function	Melanocyte-stimulating hormone receptor activity	IDA	14764818
GO:0004980	Function	Melanocyte-stimulating hormone receptor activity	IPI	19743876
GO:0005515	Function	Protein binding	IPI	19329486, 19743876, 21719532
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	TAS
GO:0006112	Process	Energy reserve metabolic process	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	TAS	8794897
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA	21873635
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA	19329486, 19743876
GO:0007631	Process	Feeding behavior	IEA
GO:0016021	Component	Integral component of membrane	IEA
GO:0017046	Function	Peptide hormone binding	IEA
GO:0019222	Process	Regulation of metabolic process	IBA	21873635
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	19737927
GO:0042923	Function	Neuropeptide binding	IMP	15927146
GO:0045780	Process	Positive regulation of bone resorption	IMP	16614075
GO:2000252	Process	Negative regulation of feeding behavior	IEA
GO:2000821	Process	Regulation of grooming behavior	IEA

Other IDs

• MIM: 155541
• HGNC: 6932
• e!Ensembl: ENSG00000166603

Protein

• UniProt ID: P32245
• Protein name: Melanocortin receptor 4 (MC4-R)
• Protein function: Hormone receptor that acts as a key component of the leptin-melanocortin pathway at the intersection of homeostatic maintenance of energetic state (PubMed:32327598, PubMed:33858992). Plays a role in regulating food intake: activation by a stimul
• PDB: 6W25, 7AUE, 7F53, 7F54, 7F55, 7F58, 7PIU, 7PIV, 8QJ2, 8WKY, 8WKZ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	61 → 302	7 transmembrane receptor (rhodopsin family)	Family

• Sequence:

  MVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLL
  ENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVN
  IDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVS
  GILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGAN
  MKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPL
  IYALRSQELRKTFKEIICCYPLGGLCDLSSRY

• Sequence length: 332

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

Causal
Disease name	Disease term	dbSNP ID	References
Diabetes mellitus	Diabetes Mellitus, Non-Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs1553638903, rs1553638909, rs948820149, rs371977235, rs1553784995, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261
Hyperinsulinism	Hyperinsulinism	rs387906407, rs151344623, rs121913156, rs137853245, rs80356655, rs104894010, rs104894012, rs104894014, rs104894015, rs137852676, rs587783169, rs72559716, rs541269678, rs151344624, rs797045209, rs761749884, rs797045624, rs863225280, rs139964066, rs1057516281, rs1057516317, rs576684889, rs201682634, rs1350717554, rs768951263, rs1260178539, rs200670692, rs72559734, rs1400535021, rs372307320, rs1554923999, rs751279984, rs1008906426, rs367850779, rs1382448285, rs1564977373, rs750586210, rs1599937180	23251400
Hypertension	Hypertensive disease	rs13306026, rs13333226
Monogenic diabetes	Monogenic diabetes	rs137852673, rs137853334, rs137853335, rs137853336, rs1600731198, rs137853338, rs587776825, rs137853236, rs137853237, rs137853238, rs2135818776, rs1566092470, rs137853243, rs137853244, rs137853245, rs80356655, rs104894008, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs193922254, rs193922257, rs193922258, rs193922260, rs193922262, rs193922263, rs193922264, rs193922265, rs193922266, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922280, rs193922282, rs193922283, rs193922284, rs193922286, rs193922289, rs193922291, rs193922297, rs193922300, rs193922302, rs193922311, rs193922313, rs193922315, rs193922317, rs193922319, rs193922335, rs193922471, rs193922475, rs193922476, rs193922479, rs193922480, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs267607555, rs587780343, rs587780344, rs587780346, rs587780357, rs794727236, rs794727775, rs794727839, rs759072800, rs797045595, rs864321656, rs777870079, rs769268803, rs886039544, rs886039386, rs886042610, rs754728827, rs1057517745, rs1057520109, rs1057521092, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524896, rs1057524898, rs1057524900, rs1057524901, rs1057524902, rs1057524903, rs1057524904, rs1057524905, rs764232985, rs1057524908, rs1064795242, rs1064793134, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307455, rs1085307913, rs765432081, rs1131692182, rs1554335441, rs762263694, rs767565869, rs1375656631, rs370375148, rs1554335616, rs769518471, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs776489992, rs1554334539, rs1554334546, rs1400535021, rs1554334610, rs1554334613, rs1415041911, rs556581174, rs1554334894, rs1554334905, rs1554335111, rs104894011, rs1554335132, rs1332966015, rs746913146, rs1554335573, rs1554335966, rs1555260207, rs1555210478, rs753998395, rs1555211426, rs1555211436, rs1555211922, rs1555211999, rs1555212014, rs1555816615, rs1555816642, rs781364316, rs1555817727, rs1555817851, rs1555211904, rs1555211975, rs779184183, rs1555815158, rs1555212396, rs1555815396, rs1555813342, rs1555815393, rs1555813267, rs1236613475, rs954727530, rs369841551, rs771108132, rs1566092307, rs1562711915, rs1185622190, rs1167124132, rs1471992838, rs1562713041, rs193922340, rs556436603, rs1562715657, rs1562717053, rs1562718043, rs193922292, rs1444739794, rs1486280029, rs193922401, rs1565883507, rs1172328722, rs1286294151, rs1565886545, rs1375557127, rs1568731279, rs1392795567, rs1229650809, rs1476637197, rs1583590393, rs1583591700, rs1583591809, rs1583596522, rs766956862, rs1290868034, rs1191912908, rs1593058932, rs2096270755, rs1364708195, rs1877324101	10199800, 27654141, 10592235, 12646665
Obesity	Obesity, Obesity, Morbid, Obesity due to melanocortin 4 receptor deficiency	rs34911341, rs74315349, rs1474810899, rs2282440, rs2491132, rs121918111, rs796065034, rs753856820, rs796065035, rs121918112, rs104894023, rs137852821, rs1580764441, rs137852822, rs137852823, rs137852824, rs13447324, rs121913562, rs121913564, rs74315393, rs121913556, rs2989924, rs193922650, rs193922685, rs193922687, rs751160202, rs1421085, rs747681609, rs1553400259, rs13447339, rs370479598, rs1554394014, rs1553174844, rs756232889, rs369841551, rs1557670950, rs1571321748, rs148538980, rs1572820988, rs1591461970, rs1419374563, rs745921568, rs144159890, rs1570714352, rs779783209, rs1573250294, rs1573254045, rs1580744791, rs1580746829, rs6548238, rs7138803, rs7754840	18559663, 14764818, 23251400, 17143585, 16507637, 18454148, 10199800, 25163632, 11487744, 11443223, 12588803, 12970296, 20966905, 15448103, 10903343, 18801902, 12646665, 15486053, 14671178, 25332687, 19151714, 12690102, 20631012, 26179253, 19079261, 19301229, 22463805, 16274851, 19091795, 19079260, 17628007, 29273807, 29311635, 10903343

Unknown
Disease name	Disease term	dbSNP ID	References
Acanthosis nigricans	Acanthosis Nigricans	rs780668
Anhedonia	Anhedonia		22785313
Compensatory hyperinsulinemia	Compensatory Hyperinsulinemia		23251400
Endogenous hyperinsulinism	Endogenous Hyperinsulinism		23251400
Exogenous hyperinsulinism	Exogenous Hyperinsulinism		23251400
Hyperglycemia	Hyperglycemia		10199800, 12646665, 10592235, 27654141
Mental depression	Mental Depression, Depressive disorder	rs587778876, rs587778877	18502874, 24827639, 18502874
Osteosclerosis	Osteosclerosis