MC4R (melanocortin 4 receptor)

Gene

• Entrez ID: 4160
• Gene name: Melanocortin 4 receptor
• Gene symbol: MC4R
• Synonyms (NCBI Gene): 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:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004977	Function	Melanocortin receptor activity	IEA
GO:0004977	Function	Melanocortin receptor activity	TAS	8794897
GO:0004980	Function	Melanocyte-stimulating hormone receptor activity	IBA
GO:0004980	Function	Melanocyte-stimulating hormone receptor activity	IDA	14764818
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, 21719532
GO:0005737	Component	Cytoplasm	IBA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	10585465
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
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
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:0007631	Process	Feeding behavior	IEA
GO:0007631	Process	Feeding behavior	TAS	9771698
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	TAS	8392067
GO:0019222	Process	Regulation of metabolic process	IEA
GO:0030073	Process	Insulin secretion	IEA
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	19737927
GO:0032094	Process	Response to food	IEA
GO:0032868	Process	Response to insulin	IEA
GO:0042923	Function	Neuropeptide binding	IMP	15927146
GO:0045780	Process	Positive regulation of bone resorption	IEA
GO:0045780	Process	Positive regulation of bone resorption	IMP	16614075
GO:0060259	Process	Regulation of feeding behavior	IBA
GO:1903998	Process	Regulation of eating behavior	IEA
GO:1903998	Process	Regulation of eating behavior	ISS
GO:1990680	Process	Response to melanocyte-stimulating hormone	IEA
GO:1990680	Process	Response to melanocyte-stimulating hormone	ISS

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

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

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)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20	Likely pathogenic; Pathogenic	rs13447332, rs2143967167, rs769342968, rs2143967182, rs746241281, rs13447338, rs2143966223, rs13447324, rs121913558, rs121913559, rs121913562, rs121913564, rs121917829, rs121913565, rs121913566, rs777077280, rs747681609, rs1057517991, rs13447339, rs370479598, rs193922687, rs369841551, rs1435358988, rs13447333, rs1380965800	RCV001823788 RCV001733857 RCV001783633 RCV001823842 RCV002468457 RCV000015392 RCV000015393 RCV002504792 RCV000015397 RCV000015398 RCV000768578 RCV000015407 RCV000015408 RCV000015409 RCV000015410 RCV000015411 RCV002288974 RCV001753845 RCV000015413 RCV003144296 RCV002496462 RCV001262853 RCV001253485 RCV001253592 RCV001253372	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Early onset severe obesity	Pathogenic; Likely pathogenic	rs121913562, rs747681609, rs1057517991, rs370479598	RCV006439574 RCV006441910 RCV006443339 RCV006438116	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MC4R-related disorder	Likely pathogenic; Pathogenic	rs2143966828, rs13447332, rs2143967167, rs895704914, rs1333647919, rs121913559, rs13447338, rs121913562, rs747681609, rs1057517991, rs13447339, rs370479598, rs193922687, rs369841551, rs1915335064	RCV003394011 RCV003416408 RCV004749726 RCV004749741 RCV003417116 RCV003402630 RCV003407336 RCV004748523 RCV004748735 RCV004748749 RCV003935293 RCV003409697 RCV003415745 RCV004748902 RCV004749625	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Monogenic diabetes	Likely pathogenic; Pathogenic	rs369841551	RCV000754806	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Obesity	Likely pathogenic; Pathogenic	rs1288335099, rs1056909320, rs13447324, rs121913562, rs121913564, rs747681609, rs13447339, rs370479598, rs193922685, rs193922687, rs756232889, rs369841551	RCV002464551 RCV002464552 RCV000015394 RCV000015405 RCV000778539 RCV000332082 RCV001249014 RCV000583759 RCV000030155 RCV000030159 RCV000582923 RCV000709738	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity due to melanocortin 4 receptor deficiency	Likely pathogenic; Pathogenic	rs2143966828, rs13447332, rs13447324, rs121913562, rs121913564, rs121917829, rs121913566, rs1226923092, rs767325252, rs1568178659, rs747681609, rs370479598, rs193922687	RCV006249747 RCV004017856 RCV004017247 RCV004017248 RCV004017249 RCV004017250 RCV004017251 RCV004018393 RCV004018394 RCV004018395 RCV004017591 RCV004017653 RCV004017270	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity, autosomal dominant	Pathogenic; Likely pathogenic	rs751160202, rs13447339, rs370479598	RCV000194758 RCV000500812 RCV000501559	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Schizophrenia	Pathogenic	rs13447324	RCV000202583	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANHEDONIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BODY WEIGHT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOVASCULAR DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC LYMPHOCYTIC LEUKEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DENTAL CARIES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GALLSTONES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERINSULINISM	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Inherited obesity	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSULIN RESISTANCE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MC4R POLYMORPHISM	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL DEPRESSION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MORBID OBESITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY, MORBID	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY, RESISTANCE TO	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, HIP	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, KNEE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYSTIC OVARY SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acanthosis Nigricans	Acanthosis Nigricans	HPO_DG			★☆☆☆☆ Found in Text Mining only
Adult Craniopharyngioma	Craniopharyngioma	BEFREE	19766264		★☆☆☆☆ Found in Text Mining only
Alopecia	Alopecia	BEFREE	23124548		★☆☆☆☆ Found in Text Mining only
Alstrom Syndrome	Alstrom syndrome	Pubtator	36356613	Associate	★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	29030576		★☆☆☆☆ Found in Text Mining only
Anhedonia	Anhedonia	PSYGENET_DG	22785313		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anorexia	Anorexia	BEFREE	12851326, 29099963, 29363944		★☆☆☆☆ Found in Text Mining only
Anorexia	Anorexia	Pubtator	36323255	Stimulate	★☆☆☆☆ Found in Text Mining only
Anorexia Nervosa	Anorexia	BEFREE	10199800, 11326303, 25419636, 30755592		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	20190196, 30863280		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety disorder	Pubtator	36123585	Associate	★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	20190196, 30863280		★☆☆☆☆ Found in Text Mining only
Apraxias	Apraxia	Pubtator	36356613	Associate	★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	17587397		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	28614768		★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	18839399, 28426141	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	26504195		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	17587397		★☆☆☆☆ Found in Text Mining only
Attention Deficit Disorder with Hyperactivity	Attention deficit hyperactivity disorder	Pubtator	23493066	Associate	★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	18777518, 21211528, 23493066, 25466298		★☆☆☆☆ Found in Text Mining only
Avoidant Restrictive Food Intake Disorder	Avoidant restrictive food intake disorder	Pubtator	36592795	Inhibit	★☆☆☆☆ Found in Text Mining only
Binge Eating Disorder	Binge eating disorder	Pubtator	21710454	Associate	★☆☆☆☆ Found in Text Mining only
Body Weight	Body weight	Pubtator	21347432, 36009013	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	21688152, 24091943, 26865587		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	21688152, 26865587	Associate	★☆☆☆☆ Found in Text Mining only
Bulimia	Bulimia	BEFREE	12646666, 15585384, 16030156, 16507637, 18777518, 25419636, 25948074, 27222505, 30306707		★☆☆☆☆ Found in Text Mining only
Bulimia	Bulimia	Pubtator	12646666	Associate	★☆☆☆☆ Found in Text Mining only
Bulimia Nervosa	Bulimia	BEFREE	10199800, 12140789, 25419636		★☆☆☆☆ Found in Text Mining only
Bulimia Nervosa	Bulimia	LHGDN	12140789		★☆☆☆☆ Found in Text Mining only
Carbohydrate Metabolism Inborn Errors	Carbohydrate metabolism disease	Pubtator	35292917	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	BEFREE	28829041		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	32807123, 33284034, 36050672	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Cerebral Infarction	BEFREE	31840601		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	21921652, 27701175		★☆☆☆☆ Found in Text Mining only
Cholelithiasis	Cholelithiasis	BEFREE	28799434		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	27449576, 28537674		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	19050674, 27449576		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	28537674	Associate	★☆☆☆☆ Found in Text Mining only
Compensatory Hyperinsulinemia	Compensatory Hyperinsulinemia	CTD_human_DG	23251400		★☆☆☆☆ Found in Text Mining only
Congenital Hyperinsulinism	Congenital hyperinsulinism	Pubtator	18835933	Associate	★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	28829041		★☆☆☆☆ Found in Text Mining only
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	21625854, 31002796		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	21625854, 31002796		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	Pubtator	31002796	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	Pubtator	34672391	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary heart disease	Coronary Heart Disease	BEFREE	21625854, 29800275, 31002796		★☆☆☆☆ Found in Text Mining only
Craniopharyngioma	Craniopharyngioma	BEFREE	19766264		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	PSYGENET_DG	18502874		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive Disorder	Major depressive disorder	Pubtator	24827639, 36123585, 37072742, 37311812	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive disorder	Mental Depression	BEFREE	31609059		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes	Diabetes	BEFREE	11246450, 11443223, 18541994, 18697794, 22466342, 23159449, 23512951, 26666384, 28409883, 29351428, 30503832		★☆☆☆☆ Found in Text Mining only
Diabetes Gestational	Gestational diabetes	Pubtator	31271198, 39458497	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Gestational	Gestational diabetes	Pubtator	32390949	Stimulate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	11246450, 11443223, 18541994, 18697794, 22466342, 23159449, 23512951, 26666384, 28409883, 29351428, 30503832		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	21976721, 23512951, 23849767, 32807123, 36585034, 37070693	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	19680233, 20161779, 21976721, 22106157, 22421923, 23130628, 23849767, 25093408, 26308479, 26680479, 31167208, 31947684, 32952152, 33205056, 33542413, 33706321, 34672391, 34696776, 35095762, 35292917, 35955479	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	31002796	Inhibit	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	30503832		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	11397906, 11692184, 19073769, 19255736, 19680233, 19844209, 20161779, 20462274, 21921652, 22106157, 22421923, 22463974, 22869321, 23130628, 23457408, 23727064, 23849767, 24151814, 25093408, 25501231, 25760438, 25951451, 26308479, 26666384, 28035522, 29717269, 31167208		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathies	Diabetic neuropathy	Pubtator	32952152	Associate	★☆☆☆☆ Found in Text Mining only
Dyslipidemias	Dyslipidemias	BEFREE	29454748, 29800275		★☆☆☆☆ Found in Text Mining only
Eating Disorders	Eating Disorders	BEFREE	18777518, 25419636, 30755592		★☆☆☆☆ Found in Text Mining only
Endogenous Hyperinsulinism	Endogenous Hyperinsulinism	CTD_human_DG	23251400		★☆☆☆☆ Found in Text Mining only
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	21347432		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	21347432, 21976109	Associate	★☆☆☆☆ Found in Text Mining only
Exogenous Hyperinsulinism	Exogenous Hyperinsulinism	CTD_human_DG	23251400		★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	BEFREE	28003536, 29402900		★☆☆☆☆ Found in Text Mining only
Fatty Liver Disease	Fatty Liver	BEFREE	28303974, 29202448, 29402900, 29802399, 30465867, 31629472		★☆☆☆☆ Found in Text Mining only
Female sexual dysfunction	Female sexual dysfunction	BEFREE	27977473		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	28303974, 29802399		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	28150230, 28791594		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	28150230	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	28150230, 28791594		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	28150230	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	25747306		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	30134862	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	34036349	Associate	★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	28829041		★☆☆☆☆ Found in Text Mining only
Hyperandrogenism	Hyperandrogenism	BEFREE	15533382		★☆☆☆☆ Found in Text Mining only
Hyperandrogenism	Hyperandrogenism	LHGDN	15533382		★☆☆☆☆ Found in Text Mining only
Hyperandrogenism	Hyperandrogenism	Pubtator	15533382	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	10078568, 30698681		★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	CLINVAR_DG	10199800, 10592235, 12646665, 27654141		★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	Pubtator	10903343, 12646665, 19092146	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperinsulinism	Hyperinsulinism	BEFREE	15126516, 19092146, 19214805, 19646498, 21047921, 21372613, 22463805, 28003536		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperinsulinism	Hyperinsulinism	CTD_human_DG	23251400		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperinsulinism	Hyperinsulinism	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperprolactinemia	Hyperprolactinemia	BEFREE	26682995		★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	19092146, 23849767, 26324055, 27701175, 32733386, 36323255	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	BEFREE	19092146, 19470880, 20147580, 21062377, 23374353, 23588626, 23849767, 26324055, 27701175, 27791019, 28274841, 28829041, 30466186, 30571561, 31028563		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	LHGDN	19092146		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoadiponectinemia	Hypoadiponectinemia	BEFREE	18070757		★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	BEFREE	30503832		★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	BEFREE	21921657		★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	Pubtator	21921657	Associate	★☆☆☆☆ Found in Text Mining only
Hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	BEFREE	21921657		★☆☆☆☆ Found in Text Mining only
Infantile Spasm	Infantile Spasms	BEFREE	18461507		★☆☆☆☆ Found in Text Mining only
Insulin Resistance	Diabetes mellitus, type 2	Pubtator	19680233, 21976721, 23101478, 26680479, 28218067, 31271198, 33468396	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ischemic Attack Transient	Transient ischemic attack	Pubtator	21921652	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure Chronic	Kidney failure	Pubtator	32952152	Associate	★☆☆☆☆ Found in Text Mining only
LEPTIN RECEPTOR DEFICIENCY	LEPTIN RECEPTOR DEFICIENCY	BEFREE	29736023, 30642682		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	29454748		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	29402900		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	21688152, 24091943, 26865587		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of endometrium	Endometrial Cancer	BEFREE	21347432		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	27449576, 28537674		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	19713740		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	PSYGENET_DG	18502874, 24827639		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mental Depression	Mental Depression	BEFREE	31609059		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mental disorders	Mental Disorders	BEFREE	30306707		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	15774557, 31305461		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic syndrome	Pubtator	31305461, 32733386, 32955223, 36050672	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome	Metabolic syndrome	Pubtator	18239646, 19629057, 22566560, 23101478, 23890480, 26965781, 28356726, 29315078, 29598821, 31002796, 31305461, 31502573, 34205732, 36440355	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	15585384, 18239646, 23054017, 23101478, 23817596, 23890480, 26965781, 28975585, 30584439, 31502573		★☆☆☆☆ Found in Text Mining only
Monogenic diabetes	Monogenic Diabetes	CLINVAR_DG	10199800, 10592235, 12646665, 27654141		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Multiple Sclerosis	Multiple Sclerosis	BEFREE	28877366, 31636637		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	31636637	Stimulate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	19713740, 28150230		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	31636637	Associate	★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	24458218, 30465867		★☆☆☆☆ Found in Text Mining only
Nonalcoholic Steatohepatitis	Non-alcoholic Fatty Liver Disease	BEFREE	30465867, 31629472		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	10078568, 10199800, 10508193, 10577903, 10585465, 10598807, 10885325, 10903341, 10903343, 11246450, 11397906, 11443223, 11692184, 11704425, 11756348, 12140789, 12364415, 12499395, 12646665, 12690102, 12851297, 12851318, 12970296, 14504270, 14633860, 14633862, 14671178, 14764812, 14764818, 14973783, 15448103, 15486053, 15489963, 15585384, 15680471, 15805150, 15951321, 15975705, 16030156, 16083993, 16231025, 16274851, 16469222, 16492696, 16507637, 16710097, 16886960, 17143585, 17185898, 17286227, 17356525, 17492953, 17517245, 17519222, 17579204, 17587397, 17628007, 17941900, 18239646, 18377640, 18388690, 18454148, 18492813, 18541994, 18559663, 18682847, 18697794, 18777518, 18801902, 18837289, 18997677, 19019037, 19050674, 19073769, 19091795, 19151714, 19153581, 19244934, 19255736, 19265794, 19283510, 19284607, 19301229, 19646498, 19668254, 19680233, 19696756, 19713740, 19803416, 19851340, 20061430, 20070976, 20147580, 20190196, 20214954, 20215774, 20374728, 20462274, 20530052, 20616199, 20725061, 20826565, 20957447, 20966905, 21047921, 21062377, 21063808, 21085626, 21094029, 21147891, 21283731, 21303735, 21311511, 21347432, 21372613, 21404042, 21527513, 21544081, 21625854, 21688152, 21720444, 21738238, 21796137, 21818152, 21913964, 21976721, 22020349, 22041983, 22083549, 22310352, 22421923, 22447289, 22463805, 22466342, 22511254, 22535749, 22566560, 22688572, 22695173, 22869321, 22989167, 23049848, 23124548, 23130628, 23146882, 23147118, 23151679, 23280863, 23284998, 23317785, 23375129, 23424664, 23428688, 23447422, 23460509, 23505181, 23754400, 23843577, 23849767, 23869016, 23950976, 24064335, 24081231, 24139164, 24151814, 24307561, 24385306, 24426828, 24458218, 24518831, 24521865, 24670271, 24705671, 24820477, 24827639, 25062455, 25093408, 25103139, 25115458, 25163632, 25332687, 25419636, 25466298, 25501231, 25514066, 25641693, 25747306, 25769385, 25948074, 26047380, 26226973, 26244670, 26588347, 26666384, 26680479, 26865587, 26907388, 26939593, 26948330, 27005443, 27241181, 27377581, 27394708, 27449576, 27551991, 27654141, 27730429, 27791019, 27849360, 28003536, 28081251, 28090739, 28148682, 28274841, 28284973, 28333235, 28384342, 28396685, 28499988, 28537674, 28579220, 28755272, 28829041, 28852042, 28878020, 28924523, 28930194, 28975585, 29097517, 29216354, 29296625, 29311635, 29329999, 29454748, 29466028, 29568105, 29726959, 29861388, 29893663, 29910730, 30048591, 30068297, 30121879, 30306707, 30465867, 30466186, 30641221, 30642682, 30755592, 30756300, 30811542, 30894367, 30896429, 30945034, 30981838, 31002796, 31035493, 31167208, 31305461, 31350533, 31429705, 31471646, 31502573, 31529534, 31666192, 31781208, 31841602, 9267995, 9620771		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity	Obesity	CLINVAR_DG	10199800, 10903343, 12588803, 12646665, 12690102, 12970296, 15448103, 15486053, 16274851, 16507637, 17628007, 18559663, 18801902, 19091795, 19301229, 20631012, 20966905, 22463805, 25332687, 26179253		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity	Obesity	UNIPROT_DG	10199800, 11443223, 11487744, 12588803, 12646665, 14671178, 14764818, 15486053, 25163632		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity	Obesity	Pubtator	10577903, 10903341, 10903343, 12629567, 12646665, 12646666, 14504270, 15115780, 15805150, 15951321, 17030971, 18239646, 18377640, 18454148, 18559663, 18682847, 18779298, 18835933, 18997677, 19016587, 19073769, 19091795, 19092146, 19164386, 19265794, 19284607, 19298524, 19629057, 19680233, 19692490, 19812171, 19889825, 20054173, 20070976, 20520848, 20530052, 20616199, 20631012, 20725061, 20843981, 20957447, 20966905, 21085626, 21283731, 21347432, 21372613, 21404042, 21544599, 21688152, 21710454, 21719532, 21720444, 21729752, 21738238, 21779088, 21921652, 21976109, 21976721, 22051089, 22095114, 22344221, 22421923, 22447289, 22511254, 22513296, 22566560, 22695173, 23130628, 23185251, 23251400, 23284998, 23316086, 23349760, 23375129, 23408508, 23493066, 23505181, 23512951, 23740648, 23791567, 23820787, 23849767, 23874820, 23950976, 24040077, 24066140, 24426828, 24518831, 24705671, 24827639, 25062455, 25072390, 25076858, 25093408, 25103139, 25332687, 25402378, 25753114, 26047380, 26179253, 26226973, 26680479, 26711810, 26782456, 26849546, 26865587, 27241181, 27394708, 27421018, 27449576, 27486100, 27634552, 27701175, 27706562, 28025578, 28081251, 28090739, 28148682, 28218067, 28377240, 28472148, 28520814, 28537674, 28852042, 29220676, 29679223, 29726959, 29861388, 29972795, 29991773, 30048591, 30068297, 30442103, 30811542, 30896429, 30945034, 30991789, 31002796, 31035493, 31167208, 31305461, 31350533, 31429705, 31742438, 31936053, 31969346, 32019489, 32059383, 32153512, 32185475, 32228543, 32327598, 32673455, 32692746, 32733386, 32770936, 32921795, 32952152, 33076233, 33205056, 33284034, 33299884, 33542413, 33621651, 33767672, 33801339, 33859285, 33862146, 33983957, 34036349, 34045736, 34205732, 34239499, 34414818, 34769477, 34836030, 35026759, 35095762, 35292917, 35574020, 35627568, 35741707, 35807283, 35809703, 36009013, 36050672, 36123585, 36323255, 36324080, 36356613, 36440355, 36553534, 36692018, 36757449, 36864747, 36921152, 37040537, 37070693, 37072742, 37329217, 37473986, 37500675, 37716291, 38002939, 38003551, 38066615, 38239988, 38279121, 38567654, 39203789, 40246357, 9392003	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity	Obesity	CTD_human_DG	17143585, 18454148, 19079260, 19079261, 19151714, 23251400		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity	Obesity	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity	Obesity	HPO_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity Abdominal	Obesity	Pubtator	23424664, 23890480, 28356726, 31035493, 31502573	Associate	★☆☆☆☆ Found in Text Mining only
Obesity due to melanocortin 4 receptor deficiency	Obesity	ORPHANET_DG	10903343		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity due to melanocortin 4 receptor deficiency	Obesity	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Obesity Morbid	Obesity	Pubtator	10903341, 10903343, 23251400, 24426828, 28377240, 30068297, 33205056, 33621651, 38003551	Associate	★☆☆☆☆ Found in Text Mining only
Obesity, Morbid	Obesity	BEFREE	10508193, 10587584, 10903341, 10903343, 11487744, 11756348, 11924926, 12959994, 14633860, 14633862, 14671178, 15448103, 15585384, 16274851, 16507637, 17143585, 17286227, 17941900, 18231126, 18779298, 19091795, 19214805, 20966905, 22447289, 22463805, 23124548, 23251400, 23774329, 24385306, 24675148, 24780838, 25163632, 26179253, 27706562, 28284973, 29311635, 29466028, 29501261, 29726959, 29736023, 29991773, 30561082		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity, Morbid	Obesity	CTD_human_DG	29273807, 29311635		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteosclerosis	Osteosclerosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pediatric Obesity	Childhood obesity	BEFREE	11487744, 12499395, 12646665, 12959994, 16507637, 17492953, 19214805, 19265794, 19766264, 20406574, 23447422, 23505181, 24139164, 25402378, 25747306, 25953783, 26179253, 27926527, 29678289, 29679223, 30442103, 30811542, 30896429		★☆☆☆☆ Found in Text Mining only
Pituitary Diseases	Pituitary Diseases	BEFREE	31609059		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	20092643, 21283731, 24498077, 26032905, 31429705		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	21283731, 26680479, 31429705	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Precocious pubarche	Precocious Pubarche	BEFREE	15533382		★☆☆☆☆ Found in Text Mining only
Proopiomelanocortin Deficiency	Proopiomelanocortin Deficiency	BEFREE	27468060		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	34787056	Associate	★☆☆☆☆ Found in Text Mining only
Pseudohypoparathyroidism	Pseudohypoparathyroidism	BEFREE	20075145		★☆☆☆☆ Found in Text Mining only
Pseudohypoparathyroidism, Type Ia	Pseudohypoparathyroidism	BEFREE	29794140		★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	Pubtator	29696068	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	22310352		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Seizures	Seizures	Pubtator	23778139	Associate	★☆☆☆☆ Found in Text Mining only
Sexual Dysfunction	Sexual Dysfunction	BEFREE	29910730		★☆☆☆☆ Found in Text Mining only
Sleep Apnea Obstructive	Sleep apnea	Pubtator	24426828	Associate	★☆☆☆☆ Found in Text Mining only
Sleep Apnea, Obstructive	Sleep Apnea	BEFREE	24426828		★☆☆☆☆ Found in Text Mining only
SPHEROCYTOSIS, TYPE 1 (disorder)	Spherocytosis	BEFREE	31551683		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	28003536, 28303974, 29402900		★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	21921652	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Diseases	Thyroid disease	Pubtator	37311812	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Hormone Metabolism Abnormal	Thyroid hormone metabolism disorder	Pubtator	27920511	Associate	★☆☆☆☆ Found in Text Mining only
Transient Cerebral Ischemia	Cerebral Ischemia	BEFREE	21921652		★☆☆☆☆ Found in Text Mining only
Transient Ischemic Attack	Transient Ischemic Attack	BEFREE	21921652		★☆☆☆☆ Found in Text Mining only
Tremor	Tremor	Pubtator	18835933	Associate	★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	28333235		★☆☆☆☆ Found in Text Mining only
Uremia	Uremia	BEFREE	15931394		★☆☆☆☆ Found in Text Mining only
West Syndrome	West Syndrome	BEFREE	18461507		★☆☆☆☆ Found in Text Mining only
West Syndrome	West Syndrome	LHGDN	18461507		★☆☆☆☆ Found in Text Mining only