MELANOCORTIN SYSTEM PATHWAY (PW:0000365)
Description
The melanocortin peptides - a collective term for the alpha-, beta- and gamma-melanocyte-stimulating hormones and the adenocorticotropin hormone (ACTH) - are derived from the sequential processing of the pro-opiomelanocortin (POMC) gene product. They bind to specific G-protein coupled melanocortin receptors (Mcr) to elicit a range of responses that include anti-inflammatory and immunomodulatory effects, regulation of energy homeostasis and feeding behavior and induction of melanogenesis. The five Mc receptors have rather distinct expression patterns. MC1R (human gene shown) is expressed in skin and also immune cells; in addition to its role in melanogenesis studies have shown that it may also function in inflammation and immunoregulation. Mc3r and 4, expressed in the central nervous system (CNS) and the brain are known regulators of energy homeostasis. Mc3r, also expressed in other tissues and Mc5r in peripheral, play a role in inflammation and immunity. Mc2r is the only receptor that exclusively binds the ACTH peptide; the others appear to bind all POMC derived peptides but with distinct affinities. A distinguishing feature of the system is the presence of natural antagonists. Asip acts as an antagonist of MC1R while Agrp is an antagonist of Mc3r and Mc4r. As the exclusive ACTH binder, Mc2r is an important effector of the hypothalamus-pituitary-adenal (HPA) axis which responds to various stresses and whose end effect is the stimulation of glucocorticoid synthesis. Activation of HPA axis leads to release of corticotropin-releasing hormone (CRH) from the hypothalamus. CRH signaling activates protein kinase A (PKA) pathway leading to expression of POMC gene and the release of ACTH. Melanocortin receptors couple to G alphas family of heterotrimeric G proteins that stimulates adenylyl cyclases; cAMP production activates PKA pathway. Mc2r requires an additional factor - Mrap, which assists in the trafficking of the receptor to the cell surface. Mrap binding the other receptors appears to have an inhibitory effect (not shown). A second Mrap-related human protein - MRAP2, appears to promote similar inhibitory effects on the receptors, except for Mc2r; its exact role in the function of Mc2r remains to be established. Other accessory proteins include Atrn and the Atrn-related, Atrnl. Atrn may act as a co-receptor for Asip while Atrnl is a binding partner for Mc4r. An intracellular protein that may also be involved in the inhibition of MC1R signaling (and possibly Mc4r) is Mgrn1. Some syndecans may act as co-receptors for Agrp (not shown). ACTH-mediated pathway is subject to inhibition by the negative feedback loop provided by the cortisol signaling pathway. The nuclear glucocorticoid receptor forms a complex with a mediator of POMC expression, the orphan nuclear receptor Nr4a1. The complex is stabilized by Smarca4 and recruits Hdac2 to silence gene expression.
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Pathway Diagram:
Genes in Pathway:
G
a nonagouti
TAS RGD
PMID:15189116 RGD:1357925
NCBI chr 2:154,792,519...154,892,932
G
Adcy2 adenylate cyclase 2
ISO SMPDB SMP:00310
NCBI chr13:68,768,162...69,147,719
G
Agrp agouti related neuropeptide
ISO RGD
PMID:15189116 RGD:1357925
NCBI chr 8:106,293,327...106,306,477
G
Atrn attractin
TAS RGD
PMID:20654690 RGD:5144214
NCBI chr 2:130,734,363...130,872,249
G
Atrnl1 attractin like 1
TAS RGD
PMID:20654690 RGD:5144214
NCBI chr19:57,599,248...58,121,775
G
Cpe carboxypeptidase E
ISO RGD
PMID:11874690 RGD:1357926
NCBI chr 8:65,045,576...65,146,143
G
Gnas GNAS (guanine nucleotide binding protein, alpha stimulating) complex locus
ISO SMPDB PMID:20852827 SMP:00310, RGD:5144213
NCBI chr 2:174,126,113...174,188,537
G
Gnb1 guanine nucleotide binding protein (G protein), beta 1
ISO SMPDB SMP:00310
NCBI chr 4:155,575,757...155,643,726
G
Gng12 guanine nucleotide binding protein (G protein), gamma 12
ISO SMPDB SMP:00310
NCBI chr 6:66,873,381...66,998,345
G
Mc1r melanocortin 1 receptor
ISO RGD
PMID:20852827 RGD:5144213
NCBI chr 8:124,133,839...124,137,483
G
Mc2r melanocortin 2 receptor
ISO SMPDB PMID:20852827 SMP:00310, RGD:5144213
NCBI chr18:68,539,970...68,562,391
G
Mc3r melanocortin 3 receptor
ISO RGD
PMID:20852827 PMID:8415620 RGD:5144213 , RGD:69884
NCBI chr 2:172,090,412...172,093,034
G
Mc4r melanocortin 4 receptor
ISO RGD
PMID:15189116 PMID:20852827 RGD:1357925 , RGD:5144213
NCBI chr18:66,990,776...66,993,558
G
Mc5r melanocortin 5 receptor
IDA ISO RGD
PMID:9512481 PMID:20852827 RGD:1626223 , RGD:5144213
NCBI chr18:68,469,811...68,475,517
G
Mgrn1 mahogunin, ring finger 1
TAS RGD
PMID:20654690 RGD:5144214
NCBI chr16:4,703,964...4,756,160
G
Mrap melanocortin 2 receptor accessory protein
ISO RGD
PMID:20654690 RGD:5144214
NCBI chr16:90,535,095...90,546,673
G
Mrap2 melanocortin 2 receptor accessory protein 2
ISO RGD
PMID:20654690 RGD:5144214
NCBI chr 9:87,026,293...87,066,104
G
Pam peptidylglycine alpha-amidating monooxygenase
ISO RGD
PMID:11874690 RGD:1357926
NCBI chr 1:97,748,816...98,023,578
G
Pcsk1 proprotein convertase subtilisin/kexin type 1
ISO RGD
PMID:15189116 PMID:11874690 RGD:1357925 , RGD:1357926
NCBI chr13:75,237,407...75,282,980
G
Pcsk2 proprotein convertase subtilisin/kexin type 2
ISO RGD
PMID:11874690 RGD:1357926
NCBI chr 2:143,388,053...143,658,204
G
Pomc pro-opiomelanocortin-alpha
ISO SMPDB PMID:15189116 PMID:11874690 SMP:00310, RGD:1357925 , RGD:1357926
NCBI chr12:4,004,945...4,010,643
G
Prkacb protein kinase, cAMP dependent, catalytic, beta
ISO SMPDB SMP:00310
NCBI chr 3:146,435,334...146,518,691
G
Sdc1 syndecan 1
TAS RGD
PMID:15189116 RGD:1357925
NCBI chr12:8,821,396...8,843,716
G
Sdc3 syndecan 3
ISO RGD
PMID:15189116 RGD:1357925
NCBI chr 4:130,519,848...130,553,629
G
Agrp agouti related neuropeptide
ISO RGD
PMID:15189116 RGD:1357925
NCBI chr 8:106,293,327...106,306,477
G
Mc4r melanocortin 4 receptor
ISO RGD
PMID:15189116 RGD:1357925
NCBI chr18:66,990,776...66,993,558
G
Pcsk1 proprotein convertase subtilisin/kexin type 1
ISO RGD
PMID:15189116 PMID:11874690 RGD:1357925 , RGD:1357926
NCBI chr13:75,237,407...75,282,980
G
Pomc pro-opiomelanocortin-alpha
ISO RGD
PMID:15189116 PMID:11874690 RGD:1357925 , RGD:1357926
NCBI chr12:4,004,945...4,010,643
G
Sdc1 syndecan 1
TAS RGD
PMID:15189116 RGD:1357925
NCBI chr12:8,821,396...8,843,716
Altered Pathway:
Additional Elements in Pathway: (includes Gene Groups, Small Molecules, Other Pathways..etc.) Pathway corticotropin-releasing hormone signaling pathway Activation of HPA axis by various stresses leads to release of corticotropin-releasing hormone from the hypothalamus and initiation of its signaling pathway which leads to activation of POMC gene expression Pathway G protein mediated signaling via Gaphas family Based on sequence similarity, the Galpha genes have been grouped into four classes. Effectors of activated Galphas are adenylyl cyclases that catalyze the formation of cAMP Small Molecule cAMP cAMP binding to the PKA complex leads to dissociation of the catalytic subunits Pathway cortisol biosynthetic pathway Cortisol, the main C21 glucocorticoid, is primarily synthesized in the cortex of the adrenal gland. Like all steroid hormones, glucocorticoids are derived from cholesterol; their biosynthesis is tightly regulated by the hypothalamus-pituitary-gonadal axis. The chronic steroidogenic response involves the change in the expression of steroidogenic genes while the acute response involves the quick delivery of cholesterol to the site of the first enzymatic reaction Pathway protein kinase A (PKA) signaling pathway Protein kinase A (PKA) signaling is a widely used intracellular pathway and the major route for channeling the second messenger cAMP signal
Pathway Gene Annotations
Disease Annotations Associated with Genes in the melanocortin system pathway
a basal cell carcinoma , dermatitis , diabetes mellitus , disease of cellular proliferation , Edema , Failure to Thrive , Furunculosis , genetic disease , hepatic veno-occlusive disease , Hyperplasia , keratosis , Liver Neoplasms , long QT syndrome , melanoma , obesity , pigmentation disease , Prenatal Exposure Delayed Effects , Skin Neoplasms , Skin/Hair/Eye Pigmentation, Variation In, 9 , type 2 diabetes mellitus Adcy2 asthma , bipolar disorder , genetic disease Agrp autosomal dominant dyskeratosis congenita 6 , genetic disease , Hyperphagia , obesity , Thinness , type 2 diabetes mellitus Atrn Experimental Liver Cirrhosis , genetic disease , Huntington's disease-like 1 , Inosine Triphosphatase Deficiency , Nerve Degeneration , obesity , pantothenate kinase-associated neurodegeneration , Tremor Atrnl1 genetic disease Cpe BDV Syndrome , endocrine system disease , genetic disease , Insulin Resistance , Lung Neoplasms , Memory Disorders , morbid obesity , obesity , type 2 diabetes mellitus Gnas acromegaly , ACTH-independent macronodular adrenal hyperplasia , ACTH-independent macronodular adrenal hyperplasia 1 , adrenal gland hyperfunction , Adrenal Gland Neoplasms , adrenocortical carcinoma , Albright's hereditary osteodystrophy , Alzheimer's disease , B-Cell Chronic Lymphocytic Leukemia , brachydactyly , Breast Neoplasms , Cafe-au-Lait Spots , cholangiocarcinoma , Colorectal Neoplasms , Cushing Syndrome , disease of cellular proliferation , endocrine system disease , Gallstones , gastric adenocarcinoma , genetic disease , growth hormone secreting pituitary adenoma , head and neck squamous cell carcinoma , hemorrhagic disease , hepatocellular carcinoma , hereditary spastic paraplegia 4 , Heterotopic Ossification , hypertension , Hypoxia , Insulin Resistance , intellectual disability , lung adenocarcinoma , McCune Albright syndrome , melanoma , Metabolic Bone Diseases , neuroblastoma , obesity , Orthostatic Hypotension , pancreatic adenocarcinoma , pancreatic cancer , Parasitic Liver Diseases , pituitary adenoma 3 , Pituitary Neoplasms , polycystic kidney disease , polycystic ovary syndrome , Precocious Puberty , primary hyperaldosteronism , Primary Pigmented Nodular Adrenocortical Disease, 1 , progressive osseous heteroplasia , pseudohypoaldosteronism , pseudohypoparathyroidism , pseudohypoparathyroidism type IB , Pseudohypoparathyroidism Type IC , pseudopseudohypoparathyroidism , Respiration Disorders , schizophrenia , sex cord-gonadal stromal tumor , skin melanoma , Tachycardia , Uterine Cervical Neoplasms , withdrawal disorder Gnb1 acute lymphoblastic leukemia , anxiety disorder , autism spectrum disorder , autosomal dominant intellectual developmental disorder , autosomal dominant intellectual developmental disorder 42 , cerebral palsy , chromosome 1p36 deletion syndrome , cleft palate , congenital myasthenic syndrome 8 , congestive heart failure , depressive disorder , Developmental Disabilities , dilated cardiomyopathy 1LL , dystonia , Ehlers-Danlos syndrome spondylodysplastic type 2 , epilepsy , epilepsy with generalized tonic-clonic seizures , Failure to Thrive , focal epilepsy , genetic disease , Goldberg-Shprintzen syndrome , Growth Disorders , hypothyroidism , idiopathic generalized epilepsy , immunodeficiency 16 , immunodeficiency 38 , intellectual disability , Joubert syndrome 25 , Language Development Disorders , microcephaly , Muscle Hypotonia , myelodysplastic syndrome , Neurodevelopmental Disorders , pathologic nystagmus , Peroxisome Biogenesis Disorder, Complementation Group 7 , Shprintzen-Goldberg Craniosynostosis , strabismus Gng12 intellectual disability Mc1r Acute-Phase Reaction , allergic contact dermatitis , atopic dermatitis , autosomal recessive chronic granulomatous disease 4 , bacterial pneumonia , basal cell carcinoma , bilateral breast cancer , breast cancer , colitis , Cutaneous Malignant Melanoma, Susceptibility To, 1 , Experimental Melanoma , familial melanoma , Fanconi anemia , genetic disease , Hyperalgesia , Hyperoxia , Hypopigmentation , Kidney Reperfusion Injury , major depressive disorder , melanoma , oculocutaneous albinism type II , primary ciliary dyskinesia 33 , Reperfusion Injury , Seasonal Allergic Rhinitis , SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 2 , UV-Induced Skin Damage , vitiligo Mc2r Acute-Phase Reaction , chromosome 18p deletion syndrome , genetic disease , glucocorticoid deficiency 1 , Hyperoxia , hypertension , intellectual disability , Metabolic Brain Diseases, Inborn , Prostatic Neoplasms , toxic shock syndrome , West syndrome Mc3r Acute-Phase Reaction , genetic disease , obesity Mc4r Acute-Phase Reaction , Binge-Eating Disorder , Body Weight , Bradycardia , Cachexia , chromosome 18q deletion syndrome , cone-rod dystrophy , diabetes mellitus , Endotoxemia , fatty liver disease , genetic disease , Hyperalgesia , hyperinsulinism , Hyperphagia , immunodeficiency 12 , Insulin Resistance , isolated microphthalmia 3 , morbid obesity , non-alcoholic steatohepatitis , obesity , schizophrenia , sciatic neuropathy Mc5r Acute-Phase Reaction , chromosome 18p deletion syndrome , genetic disease , intellectual disability Mgrn1 epilepsy , genetic disease , hyperglycemia , hyperinsulinism , idiopathic generalized epilepsy , Kohlschutter-Tonz syndrome , obesity , Rubinstein-Taybi syndrome , short-rib thoracic dysplasia 9 with or without polydactyly Mrap adrenal gland disease , amyotrophic lateral sclerosis type 1 , autosomal dominant intellectual developmental disorder 7 , genetic disease , glucocorticoid deficiency 1 , Glucocorticoid Deficiency 2 , Parkinson's disease 20 , ZTTK Syndrome Mrap2 genetic disease , obesity Pam anxiety disorder , Brain Hypoxia , Experimental Arthritis , familial adenomatous polyposis 1 , genetic disease , Hereditary Neoplastic Syndromes , Hyperplasia , hypothyroidism , Neurodevelopmental Disorders , prostate adenocarcinoma , type 2 diabetes mellitus Pcsk1 Body Weight , Dehydration , Dwarfism , endocrine system disease , Endotoxemia , Experimental Diabetes Mellitus , familial adenomatous polyposis 1 , genetic disease , glucose intolerance , Hereditary Neoplastic Syndromes , hyperglycemia , hyperthyroidism , hypogonadism , hypothyroidism , Inflammation , islet cell tumor , morbid obesity , Neurodevelopmental Disorders , obesity , proprotein convertase 1/3 deficiency , type 1 diabetes mellitus , type 2 diabetes mellitus , visual epilepsy Pcsk2 cataract 33 , chronic kidney disease , Endotoxemia , Experimental Diabetes Mellitus , genetic disease , Inflammation , myocardial infarction , Reperfusion Injury , type 2 diabetes mellitus Pomc ACTH Syndrome, Ectopic , acute kidney failure , acute kidney tubular necrosis , Acute Liver Failure , adrenal cortex disease , Adrenal Insufficiency , amnestic disorder , autistic disorder , bipolar disorder , Body Weight , Bradycardia , Burns , calcinosis , Cardiomegaly , cardiomyopathy , Catalepsy , Cerebral Hemorrhage , cerebral palsy , cholestasis , chondrocalcinosis , Cocaine-Related Disorders , congestive heart failure , Constipation , Cushing Syndrome , cystitis , depressive disorder , diabetes insipidus , diabetes mellitus , disease by infectious agent , disease of mental health , Edema , epilepsy , epilepsy with generalized tonic-clonic seizures , Experimental Liver Cirrhosis , eye disease , Eye Pain , facial paralysis , familial Mediterranean fever , fatty liver disease , Femur Head Necrosis , Fever , gastrointestinal system disease , genetic disease , glomerulonephritis , Gouty Arthritis , Hematuria , Hemorrhage , heroin dependence , Hirsutism , Hypercalciuria , Hypernatremia , Hyperphagia , hypertension , hypertrophic cardiomyopathy , Hypocalcemia , hypokalemia , Hypotension , Hypoxia , immune system disease , Inflammation , inflammatory bowel disease , Kidney Calculi , kidney disease , long QT syndrome , melanoma , morbid obesity , multiple sclerosis , myasthenia gravis , Myocardial Ischemia , Myoclonic Epilepsies , Nausea , Necrosis , nephrocalcinosis , Neurogenic Inflammation , Nociceptive Pain , obesity , Oliguria , Opsoclonus-Myoclonus Syndrome , osteoarthritis , osteoporosis , Pain , pancreas disease , penile disease , pituitary-dependent Cushing's disease , pneumonia , Postoperative Complications , Proopiomelanocortin Deficiency , proteinuria , Recurrence , renal cell carcinoma , restless legs syndrome , Rhabdomyoma , Sacroiliitis , severe acute respiratory syndrome , sick sinus syndrome , sleep disorder , subvalvular aortic stenosis , synovitis , Tatton-Brown-Rahman syndrome , urinary tract infection , Weight Gain , Weight Loss , West syndrome , withdrawal disorder Prkacb adrenal cortical adenoma , biliary tract benign neoplasm , brain ischemia , Cardioacrofacial Dysplasia 2 , cholangiocarcinoma , Cushing Syndrome , genetic disease , Hypoglossal Nerve Injuries , Prostatic Neoplasms Sdc1 COVID-19 , familial hyperlipidemia , genetic disease , Hodgkin's lymphoma , hyperglycemia , Inflammation , long QT syndrome , lung adenocarcinoma , Lymphoma, AIDS-Related , malignant mesothelioma , myocardial infarction , obesity , proteinuria Sdc3 genetic disease , obesity
acromegaly Gnas ACTH Syndrome, Ectopic Pomc ACTH-independent macronodular adrenal hyperplasia Gnas ACTH-independent macronodular adrenal hyperplasia 1 Gnas acute kidney failure Pomc acute kidney tubular necrosis Pomc Acute Liver Failure Pomc acute lymphoblastic leukemia Gnb1 Acute-Phase Reaction Mc1r , Mc2r , Mc3r , Mc4r , Mc5r adrenal cortex disease Pomc adrenal cortical adenoma Prkacb adrenal gland disease Mrap adrenal gland hyperfunction Gnas Adrenal Gland Neoplasms Gnas Adrenal Insufficiency Pomc adrenocortical carcinoma Gnas Albright's hereditary osteodystrophy Gnas allergic contact dermatitis Mc1r Alzheimer's disease Gnas amnestic disorder Pomc amyotrophic lateral sclerosis type 1 Mrap anxiety disorder Gnb1 , Pam asthma Adcy2 atopic dermatitis Mc1r autism spectrum disorder Gnb1 autistic disorder Pomc autosomal dominant dyskeratosis congenita 6 Agrp autosomal dominant intellectual developmental disorder Gnb1 autosomal dominant intellectual developmental disorder 42 Gnb1 autosomal dominant intellectual developmental disorder 7 Mrap autosomal recessive chronic granulomatous disease 4 Mc1r B-Cell Chronic Lymphocytic Leukemia Gnas bacterial pneumonia Mc1r basal cell carcinoma a , Mc1r BDV Syndrome Cpe bilateral breast cancer Mc1r biliary tract benign neoplasm Prkacb Binge-Eating Disorder Mc4r bipolar disorder Adcy2 , Pomc Body Weight Mc4r , Pcsk1 , Pomc brachydactyly Gnas Bradycardia Mc4r , Pomc Brain Hypoxia Pam brain ischemia Prkacb breast cancer Mc1r Breast Neoplasms Gnas Burns Pomc Cachexia Mc4r Cafe-au-Lait Spots Gnas calcinosis Pomc Cardioacrofacial Dysplasia 2 Prkacb Cardiomegaly Pomc cardiomyopathy Pomc Catalepsy Pomc cataract 33 Pcsk2 Cerebral Hemorrhage Pomc cerebral palsy Gnb1 , Pomc cholangiocarcinoma Gnas , Prkacb cholestasis Pomc chondrocalcinosis Pomc chromosome 18p deletion syndrome Mc2r , Mc5r chromosome 18q deletion syndrome Mc4r chromosome 1p36 deletion syndrome Gnb1 chronic kidney disease Pcsk2 cleft palate Gnb1 Cocaine-Related Disorders Pomc colitis Mc1r Colorectal Neoplasms Gnas cone-rod dystrophy Mc4r congenital myasthenic syndrome 8 Gnb1 congestive heart failure Gnb1 , Pomc Constipation Pomc COVID-19 Sdc1 Cushing Syndrome Gnas , Pomc , Prkacb Cutaneous Malignant Melanoma, Susceptibility To, 1 Mc1r cystitis Pomc Dehydration Pcsk1 depressive disorder Gnb1 , Pomc dermatitis a Developmental Disabilities Gnb1 diabetes insipidus Pomc diabetes mellitus a , Mc4r , Pomc dilated cardiomyopathy 1LL Gnb1 disease by infectious agent Pomc disease of cellular proliferation a , Gnas disease of mental health Pomc Dwarfism Pcsk1 dystonia Gnb1 Edema a , Pomc Ehlers-Danlos syndrome spondylodysplastic type 2 Gnb1 endocrine system disease Cpe , Gnas , Pcsk1 Endotoxemia Mc4r , Pcsk1 , Pcsk2 epilepsy Gnb1 , Mgrn1 , Pomc epilepsy with generalized tonic-clonic seizures Gnb1 , Pomc Experimental Arthritis Pam Experimental Diabetes Mellitus Pcsk1 , Pcsk2 Experimental Liver Cirrhosis Atrn , Pomc Experimental Melanoma Mc1r eye disease Pomc Eye Pain Pomc facial paralysis Pomc Failure to Thrive a , Gnb1 familial adenomatous polyposis 1 Pam , Pcsk1 familial hyperlipidemia Sdc1 familial Mediterranean fever Pomc familial melanoma Mc1r Fanconi anemia Mc1r fatty liver disease Mc4r , Pomc Femur Head Necrosis Pomc Fever Pomc focal epilepsy Gnb1 Furunculosis a Gallstones Gnas gastric adenocarcinoma Gnas gastrointestinal system disease Pomc genetic disease a , Adcy2 , Agrp , Atrn , Atrnl1 , Cpe , Gnas , Gnb1 , Mc1r , Mc2r , Mc3r , Mc4r , Mc5r , Mgrn1 , Mrap , Mrap2 , Pam , Pcsk1 , Pcsk2 , Pomc , Prkacb , Sdc1 , Sdc3 glomerulonephritis Pomc glucocorticoid deficiency 1 Mc2r , Mrap Glucocorticoid Deficiency 2 Mrap glucose intolerance Pcsk1 Goldberg-Shprintzen syndrome Gnb1 Gouty Arthritis Pomc Growth Disorders Gnb1 growth hormone secreting pituitary adenoma Gnas head and neck squamous cell carcinoma Gnas Hematuria Pomc Hemorrhage Pomc hemorrhagic disease Gnas hepatic veno-occlusive disease a hepatocellular carcinoma Gnas Hereditary Neoplastic Syndromes Pam , Pcsk1 hereditary spastic paraplegia 4 Gnas heroin dependence Pomc Heterotopic Ossification Gnas Hirsutism Pomc Hodgkin's lymphoma Sdc1 Huntington's disease-like 1 Atrn Hyperalgesia Mc1r , Mc4r Hypercalciuria Pomc hyperglycemia Mgrn1 , Pcsk1 , Sdc1 hyperinsulinism Mc4r , Mgrn1 Hypernatremia Pomc Hyperoxia Mc1r , Mc2r Hyperphagia Agrp , Mc4r , Pomc Hyperplasia a , Pam hypertension Gnas , Mc2r , Pomc hyperthyroidism Pcsk1 hypertrophic cardiomyopathy Pomc Hypocalcemia Pomc Hypoglossal Nerve Injuries Prkacb hypogonadism Pcsk1 hypokalemia Pomc Hypopigmentation Mc1r Hypotension Pomc hypothyroidism Gnb1 , Pam , Pcsk1 Hypoxia Gnas , Pomc idiopathic generalized epilepsy Gnb1 , Mgrn1 immune system disease Pomc immunodeficiency 12 Mc4r immunodeficiency 16 Gnb1 immunodeficiency 38 Gnb1 Inflammation Pcsk1 , Pcsk2 , Pomc , Sdc1 inflammatory bowel disease Pomc Inosine Triphosphatase Deficiency Atrn Insulin Resistance Cpe , Gnas , Mc4r intellectual disability Gnas , Gnb1 , Gng12 , Mc2r , Mc5r islet cell tumor Pcsk1 isolated microphthalmia 3 Mc4r Joubert syndrome 25 Gnb1 keratosis a Kidney Calculi Pomc kidney disease Pomc Kidney Reperfusion Injury Mc1r Kohlschutter-Tonz syndrome Mgrn1 Language Development Disorders Gnb1 Liver Neoplasms a long QT syndrome a , Pomc , Sdc1 lung adenocarcinoma Gnas , Sdc1 Lung Neoplasms Cpe Lymphoma, AIDS-Related Sdc1 major depressive disorder Mc1r malignant mesothelioma Sdc1 McCune Albright syndrome Gnas melanoma a , Gnas , Mc1r , Pomc Memory Disorders Cpe Metabolic Bone Diseases Gnas Metabolic Brain Diseases, Inborn Mc2r microcephaly Gnb1 morbid obesity Cpe , Mc4r , Pcsk1 , Pomc multiple sclerosis Pomc Muscle Hypotonia Gnb1 myasthenia gravis Pomc myelodysplastic syndrome Gnb1 myocardial infarction Pcsk2 , Sdc1 Myocardial Ischemia Pomc Myoclonic Epilepsies Pomc Nausea Pomc Necrosis Pomc nephrocalcinosis Pomc Nerve Degeneration Atrn neuroblastoma Gnas Neurodevelopmental Disorders Gnb1 , Pam , Pcsk1 Neurogenic Inflammation Pomc Nociceptive Pain Pomc non-alcoholic steatohepatitis Mc4r obesity a , Agrp , Atrn , Cpe , Gnas , Mc3r , Mc4r , Mgrn1 , Mrap2 , Pcsk1 , Pomc , Sdc1 , Sdc3 oculocutaneous albinism type II Mc1r Oliguria Pomc Opsoclonus-Myoclonus Syndrome Pomc Orthostatic Hypotension Gnas osteoarthritis Pomc osteoporosis Pomc Pain Pomc pancreas disease Pomc pancreatic adenocarcinoma Gnas pancreatic cancer Gnas pantothenate kinase-associated neurodegeneration Atrn Parasitic Liver Diseases Gnas Parkinson's disease 20 Mrap pathologic nystagmus Gnb1 penile disease Pomc Peroxisome Biogenesis Disorder, Complementation Group 7 Gnb1 pigmentation disease a pituitary adenoma 3 Gnas Pituitary Neoplasms Gnas pituitary-dependent Cushing's disease Pomc pneumonia Pomc polycystic kidney disease Gnas polycystic ovary syndrome Gnas Postoperative Complications Pomc Precocious Puberty Gnas Prenatal Exposure Delayed Effects a primary ciliary dyskinesia 33 Mc1r primary hyperaldosteronism Gnas Primary Pigmented Nodular Adrenocortical Disease, 1 Gnas progressive osseous heteroplasia Gnas Proopiomelanocortin Deficiency Pomc proprotein convertase 1/3 deficiency Pcsk1 prostate adenocarcinoma Pam Prostatic Neoplasms Mc2r , Prkacb proteinuria Pomc , Sdc1 pseudohypoaldosteronism Gnas pseudohypoparathyroidism Gnas pseudohypoparathyroidism type IB Gnas Pseudohypoparathyroidism Type IC Gnas pseudopseudohypoparathyroidism Gnas Recurrence Pomc renal cell carcinoma Pomc Reperfusion Injury Mc1r , Pcsk2 Respiration Disorders Gnas restless legs syndrome Pomc Rhabdomyoma Pomc Rubinstein-Taybi syndrome Mgrn1 Sacroiliitis Pomc schizophrenia Gnas , Mc4r sciatic neuropathy Mc4r Seasonal Allergic Rhinitis Mc1r severe acute respiratory syndrome Pomc sex cord-gonadal stromal tumor Gnas short-rib thoracic dysplasia 9 with or without polydactyly Mgrn1 Shprintzen-Goldberg Craniosynostosis Gnb1 sick sinus syndrome Pomc skin melanoma Gnas Skin Neoplasms a SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 2 Mc1r Skin/Hair/Eye Pigmentation, Variation In, 9 a sleep disorder Pomc strabismus Gnb1 subvalvular aortic stenosis Pomc synovitis Pomc Tachycardia Gnas Tatton-Brown-Rahman syndrome Pomc Thinness Agrp toxic shock syndrome Mc2r Tremor Atrn type 1 diabetes mellitus Pcsk1 type 2 diabetes mellitus a , Agrp , Cpe , Pam , Pcsk1 , Pcsk2 urinary tract infection Pomc Uterine Cervical Neoplasms Gnas UV-Induced Skin Damage Mc1r visual epilepsy Pcsk1 vitiligo Mc1r Weight Gain Pomc Weight Loss Pomc West syndrome Mc2r , Pomc withdrawal disorder Gnas , Pomc ZTTK Syndrome Mrap
