View Ontology Report


The leptin system plays an essential role in energy homeostasis - the balance between energy intake and expenditure. Leptin acts on two classes of neurons: those expressing the appetite decreasing peptides POMC and CART and those expressing the appetite stimulating peptides NPY and AgRP, promoting the upregulation of the former and downregulation of the latter. The products of the Pomc and Agrp genes act on melanocortin receptors as agonists and antagonists, respectively and the le

Pathway Diagram:

Ariadne Genomics Inc. PY1138 PY985 Stat3 Lepr --+> Jak2 Jak2 Lepr Ptpn11 Socs3 ---| Lepr Jak2 --+> Irs2 Lepr --+> the extracellular signal-regulated Raf/Mek/Erk signaling pathway Lep phosphatidylinositol 3-kinase-Akt signaling pathway leptin activated Stat3 gene targets ---> Socs3 Socs3 Ptpn1 Lepr ---- Stat3 Lep ---- Lepr Jak2 --+> Lepr Jak2 --+> Irs1 Jak2 ---- Lepr Jak2 ---- Sh2bpsm1 Irs1 ---- Sh2bpsm1 Irs2 ---- Sh2bpsm1 Jak2 ---- Ptpn11 Lepr ---- Ptpn11 Stat3 ---> leptin activated Stat3 gene targets the extracellular signal-regulated Raf/Mek/Erk signaling pathway Ptpn1 ---| Stat3 Ptpn1 ---| Jak2 Irs2 Irs1 Sh2bpsm1 Jak-Stat signaling pathway Socs3 ---| Jak2 Jak2 --+> Stat3 leptin activated Stat3 gene targets Lepr --+> phosphatidylinositol 3-kinase-Akt signaling pathway Jak2 --+> the extracellular signal-regulated Raf/Mek/Erk signaling pathway

Genes in Pathway:

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leptin system pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Irs1 insulin receptor substrate 1 JBrowse link 9 88,033,668 88,086,488 RGD:2302071
G Irs2 insulin receptor substrate 2 JBrowse link 16 83,824,515 83,848,569 RGD:2302071
G Jak2 Janus kinase 2 JBrowse link 1 247,398,667 247,457,521 RGD:1625125
G Lep leptin JBrowse link 4 56,337,695 56,351,818 RGD:61790
G Lepr leptin receptor JBrowse link 5 120,503,475 120,682,281 RGD:61790
G Lepr_v1 leptin receptor, variant 1 RGD:2290293
G Lepr_v2 leptin receptor, variant 2 RGD:2290292
G Ptpn1 protein tyrosine phosphatase, non-receptor type 1 JBrowse link 3 164,665,462 164,711,936 RGD:2289366
G Ptpn11 protein tyrosine phosphatase, non-receptor type 11 JBrowse link 12 40,895,515 40,955,999 RGD:2289807
G Sh2b1 SH2B adaptor protein 1 JBrowse link 1 197,878,839 197,888,223 RGD:2302071
G Socs3 suppressor of cytokine signaling 3 JBrowse link 10 106,973,863 106,976,969 RGD:1625125
G Stat3 signal transducer and activator of transcription 3 JBrowse link 10 88,790,401 88,842,263 RGD:1600611
altered leptin system pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Insr insulin receptor JBrowse link 12 1,682,527 1,816,414 RGD:2290473
G Lep leptin JBrowse link 4 56,337,695 56,351,818 RGD:61790
G Lepr leptin receptor JBrowse link 5 120,503,475 120,682,281 RGD:61790
G Lepr_v2 leptin receptor, variant 2 RGD:2290292

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Gene GroupLeptin activated Stat3 gene targetsLeptin activated Stat3 gene targets

Pathway Gene Annotations

Disease Annotations Associated with Genes in the leptin system pathway
Disease TermsGene Symbols
Abortion, SpontaneousJak2
adenocarcinomaPtpn11 , Stat3
adenoid cystic carcinomaStat3
adult respiratory distress syndromeLep
AIDS Dementia ComplexIrs1
Alzheimer's DiseaseIrs1 , Irs2 , Jak2 , Lep , Stat3
ankylosing spondylitisJak2
Aortic Valve StenosisPtpn11
Arthritis, ExperimentalJak2 , Lep , Socs3 , Stat3
Arthritis, RheumatoidJak2 , Stat3
atherosclerosisSocs3 , Stat3
Autistic DisorderLep , Stat3
autoimmune disease, multisystem, infantile-onsetStat3
autoimmune disease, multisystem, infantile-onset, 1Stat3
Autoimmune DiseasesStat3
Behcet SyndromeStat3
Body Weight ChangesLep
Brain InjuriesJak2 , Lep , Stat3
Brain IschemiaStat3
Brain NeoplasmsPtpn11
Breast NeoplasmsLep , Lepr , Stat3
Budd-Chiari SyndromeJak2
Carcinoma, Ductal, BreastSocs3
Carcinoma, HepatocellularIrs1 , Irs2 , Socs3
Carcinoma, Intraductal, NoninfiltratingSocs3
Carcinoma, Renal CellLep , Stat3
Carcinoma, Squamous CellPtpn11 , Stat3
Carcinoma, Squamous Cell of Head and NeckStat3
Cardiofaciocutaneous SyndromePtpn11
Cardiomyopathy, HypertrophicPtpn11
Cell Transformation, NeoplasticIrs1 , Stat3
cervical intraepithelial neoplasiaStat3
Choroidal NeovascularizationLep , Stat3
Chronic Lymphoid LeukemiaPtpn11
chronic myeloid leukemiaJak2
Chronic Myeloproliferative DisorderJak2
Churg-Strauss SyndromeStat3
Colonic NeoplasmsLep , Stat3
Colorectal NeoplasmsPtpn11
Copper-Overload CirrhosisStat3
Coronary Artery DiseaseIrs1
Coronary DiseaseIrs1
Costello syndromePtpn11
Crohn DiseaseJak2 , Lep , Stat3
Cystic FibrosisLep
Diabetes MellitusIrs1 , Lep , Lepr
diabetes mellitus, experimentalIrs1 , Irs2 , Lep , Lepr , Socs3 , Stat3
Diabetes, GestationalLep , Lepr
Diabetic NephropathiesIrs2 , Jak2 , Lep , Stat3
Diabetic NeuropathiesLepr
dilated cardiomyopathyLepr , Ptpn11
Disease Models, AnimalStat3
duodenal ulcerStat3
Endometrial NeoplasmsSocs3 , Stat3
EndotoxemiaIrs1 , Socs3
Epidermal HyperplasiaStat3
Erythrocytosis, Familial, 1Jak2
Erythrocytosis, Familial, 2Jak2
essential thrombocythemiaJak2
Experimental Encephalomyelitis, AutoimmuneJak2 , Stat3
Failure to ThrivePtpn11
Fatty LiverJak2 , Lep , Lepr , Socs3
Femoral FracturesLep
Fetal Growth RetardationIrs1 , Irs2 , Lep , Ptpn11
FibrosisLepr , Socs3 , Stat3
gastric ulcerLep
Glucose IntoleranceJak2 , Lep , Lepr
Granuloma, PyogenicStat3
Granulosa Cell TumorLepr
Growth DisordersJak2
Growth Hormone-Secreting Pituitary AdenomaPtpn11
Heart DiseasesJak2 , Stat3
Heart FailureLep , Lepr
Heart Valve DiseasesJak2
Helicobacter InfectionsSocs3
Hepatitis C, ChronicStat3
Hepatitis, AutoimmuneLep
Hepatitis, ChronicStat3
hereditary multiple exostosesPtpn11
Hernias, Diaphragmatic, CongenitalStat3
Heroin DependenceLep
HIV InfectionsSocs3
Hodgkin DiseasePtpn1
Huntington's DiseaseLep
Hyper-IgE recurrent infection syndrome, autosomal dominantStat3
HyperalgesiaJak2 , Stat3
HyperglycemiaIrs2 , Lepr
hyperinsulinismIrs1 , Lep , Lepr , Ptpn1
HyperlipidemiasIrs1 , Lep , Lepr
HyperphagiaLep , Lepr
HypertensionLep , Lepr , Ptpn1
HypertriglyceridemiaLep , Socs3
Hypertrophy, Left VentricularLepr
HyperuricemiaJak2 , Stat3
HypogonadismLep , Lepr
Idiopathic Pulmonary FibrosisStat3
Immunologic Deficiency SyndromesLepr
Infarction, Middle Cerebral ArteryStat3
Infertility, FemaleLep , Lepr
InflammationJak2 , Lep , Ptpn1 , Stat3
inherited metabolic disorderLepr
Insulin ResistanceIrs1 , Irs2 , Lep , Lepr , Ptpn1 , Socs3
Intestinal Reperfusion InjuryJak2
irritant dermatitisStat3
Job syndromeStat3
juvenile arthritisStat3
Kidney DiseasesLepr
Kidney Failure, ChronicIrs1 , Lep
Kidney Reperfusion InjuryLep
LEOPARD SyndromePtpn11
Leptin Receptor DeficiencyLepr
LeukemiaJak2 , Ptpn11
Leukemia, Myeloid, AcuteJak2 , Ptpn11 , Stat3
Leukemia, Myelomonocytic, JuvenilePtpn11
Leukemia, T-CellStat3
Leukemia-Lymphoma, Adult T-CellStat3
Liver CirrhosisStat3
Liver Cirrhosis, AlcoholicJak2
Liver Cirrhosis, BiliaryJak2 , Lep , Lepr
Liver Cirrhosis, ExperimentalJak2 , Lep , Lepr , Ptpn1
Liver DiseasesSocs3
Liver InjuryJak2 , Stat3
Liver NeoplasmsStat3
Liver Neoplasms, ExperimentalJak2 , Stat3
Liver Reperfusion InjuryJak2
lung adenocarcinomaPtpn11
Lung DiseasesLep
lung squamous cell carcinomaPtpn11
Lupus Erythematosus, SystemicJak2
Lymphatic MetastasisSocs3 , Stat3
Lymphoblastic Leukemia, Acute, with Lymphomatous FeaturesJak2
lymphocytic leukemia, chronic, B-cellPtpn11
Lymphoma, B-CellPtpn1
Lymphoma, Large-Cell, AnaplasticStat3
Lymphoma, T-CellStat3
Lymphoproliferative DisordersStat3
Mammary Neoplasms, AnimalStat3
Mammary Neoplasms, ExperimentalLep , Socs3 , Stat3
mediastinal neoplasmsPtpn1
medulloblastomaIrs2 , Stat3
Melanoma, Cutaneous MalignantStat3
Memory DisordersStat3
Mesenteric Vascular OcclusionJak2
Metabolic Syndrome XIrs1 , Lep
Multiple MyelomaPtpn11
Myeloproliferative DisordersJak2
Myocardial InfarctionJak2
Myocardial IschemiaJak2 , Lepr , Socs3
Myocardial Reperfusion InjuryJak2 , Lep , Lepr , Stat3
Nasal PolypsLepr , Stat3
Neoplasm MetastasisStat3
Nephrotic SyndromeJak2
Nerve DegenerationLep
Neurodevelopmental DisordersPtpn11
Niemann-Pick disease type C1Jak2 , Stat3
non-small cell lung carcinomaLep , Stat3
nonalcoholic fatty liver diseaseIrs1 , Irs2 , Jak2 , Lep , Stat3
Noonan like syndromePtpn11
Noonan SyndromePtpn11
Noonan syndrome 1Ptpn11
Noonan syndrome 3Ptpn11
Noonan Syndrome-Like Disorder with or without Juvenile Myelomonocytic LeukemiaPtpn11
obesityIrs1 , Irs2 , Jak2 , Lep , Lepr , Ptpn1 , Sh2b1 , Socs3 , Stat3
Obesity, MorbidLep , Lepr
Oral UlcerLep
Osteoarthritis, KneeLep , Lepr
OsteoporosisIrs1 , Irs2 , Lep , Lepr
Ovarian NeoplasmsStat3
Oxygen-Induced RetinopathyStat3
Pancreatic DiseasesLepr
Pancreatic NeoplasmsStat3
Parkinson's DiseaseLep
Pituitary DiseasesLepr
Pleomorphic Xanthoastrocytoma Lep
Pneumonia, BacterialLep , Stat3
Pneumonia, PneumococcalLep , Lepr
Polycystic Ovary SyndromeLep
polycythemia veraJak2
Pre-EclampsiaLep , Lepr
Precancerous ConditionsIrs1 , Stat3
Precursor B-Cell Lymphoblastic Leukemia-LymphomaStat3
Precursor T-Cell Lymphoblastic Leukemia-LymphomaPtpn11
Pregnancy ComplicationsJak2
Primary MyelofibrosisJak2
prostatic neoplasmsIrs1 , Jak2 , Lep , Stat3
ProteinuriaLep , Lepr
psoriatic arthritisStat3
Puberty, DelayedLepr
Pulmonary Disease, Chronic ObstructiveLep , Lepr
Pulmonary FibrosisLepr , Stat3
Reperfusion InjuryJak2 , Lep , Socs3 , Stat3
Respiratory Tract InfectionsLepr
Retina Reperfusion InjuryStat3
Retinal DetachmentJak2
Rett SyndromePtpn1
Rhabdomyosarcoma, EmbryonalPtpn11
Scleroderma, LimitedJak2
scrapieJak2 , Stat3
SepsisIrs1 , Jak2 , Lep , Socs3 , Stat3
Sepsis-Associated EncephalopathyJak2 , Stat3
short bowel syndromeLep , Lepr
Skin NeoplasmsStat3
Sleep Apnea SyndromesLepr
Sleep Apnea, ObstructiveLep , Lepr
Smith-Magenis syndromeSocs3 , Stat3
Spinal Cord InjuriesJak2 , Lep
Spinal FracturesLepr
Status EpilepticusSocs3
Stomach NeoplasmsIrs2 , Stat3
Subarachnoid HemorrhageStat3
tetralogy of FallotPtpn11
Thrombocythemia 3Jak2
Tongue NeoplasmsStat3
transient cerebral ischemiaJak2 , Stat3
type 1 diabetes mellitusStat3
type 2 diabetes mellitusIrs1 , Irs2 , Lep , Lepr , Ptpn1 , Socs3 , Stat3
ulcerative colitisJak2 , Stat3
uterine cervical neoplasmsJak2 , Stat3
Uveitis, Autoimmune, ExperimentalStat3
Uveoretinitis, Autoimmune, ExperimentalStat3
Varicose UlcerLepr
Venous ThrombosisJak2
Weight GainLep
Weight LossLep
Wilms tumorStat3
Pathway Annotations Associated with Genes in the leptin system pathway
Pathway TermsGene Symbols
acute myeloid leukemia pathwayStat3
aldosterone signaling pathwayIrs1 , Irs2 , Jak2
altered energy homeostasis pathwayLep , Lepr
altered Jak-Stat signaling pathwayJak2
altered leptin system pathwayLep , Lepr , Lepr_v2
angiotensin II signaling pathwayJak2
angiotensin II signaling pathway via AT1 receptorJak2
ceramide signaling pathwayStat3
chemokine mediated signaling pathwayJak2 , Stat3
chronic myeloid leukemia pathwayPtpn11
cytokine mediated signaling pathwayLep , Lepr
endothelin signaling pathwayJak2
energy homeostasis pathwayLep , Lepr
epidermal growth factor/neuregulin signaling pathwayPtpn1 , Ptpn11 , Stat3
erythropoietin signaling pathwayIrs2 , Jak2 , Ptpn11 , Socs3
fibroblast growth factor signaling pathwayPtpn11
granulocyte-macrophage colony-stimulating factor signaling pathwayJak2 , Ptpn11 , Stat3
growth hormone signaling pathwayJak2
hepatitis C pathwaySocs3 , Stat3
hypoxia inducible factor pathwayLep
influenza A pathwayJak2 , Socs3
insulin signaling pathwayIrs1 , Irs2 , Ptpn1 , Ptpn11 , Socs3
insulin-like growth factor signaling pathwayIrs1 , Irs2 , Ptpn1 , Ptpn11
Interleukin-10 signaling pathwayStat3
interleukin-12 signaling pathwayJak2 , Stat3
interleukin-2 signaling pathwayIrs1 , Irs2 , Ptpn11 , Socs3 , Stat3
interleukin-23 signaling pathwayJak2 , Socs3 , Stat3
interleukin-27 signaling pathwayJak2 , Stat3
interleukin-3 signaling pathwayJak2 , Ptpn11
interleukin-4 signaling pathwayIrs1 , Irs2 , Jak2 , Socs3
interleukin-5 signaling pathwayJak2 , Ptpn11
interleukin-6 signaling pathwayJak2 , Ptpn11 , Socs3 , Stat3
Jak-Stat signaling pathwayJak2 , Lep , Lepr , Ptpn1 , Ptpn11 , Socs3 , Stat3
Leishmaniasis pathwayJak2
leptin system pathwayIrs1 , Irs2 , Jak2 , Lep , Lepr , Lepr_v1 , Lepr_v2 , Ptpn1 , Ptpn11 , Sh2b1 , Socs3 , Stat3
measles pathwayJak2 , Stat3
mTOR signaling pathwayIrs1
N-cadherin signaling pathwayPtpn1 , Ptpn11
neurotrophic factor signaling pathwayIrs1 , Irs2 , Ptpn11 , Sh2b1
obesity pathwayLepr , Lepr_v2
pancreatic cancer pathwayStat3
platelet-derived growth factor signaling pathwayJak2 , Ptpn1 , Ptpn11 , Stat3
renal cell carcinoma pathwayPtpn11
scatter factor/hepatocyte growth factor signaling pathwayPtpn11
somatostatin signaling pathwayJak2 , Ptpn11
sphingosine 1-phosphate signaling pathwayIrs1 , Jak2
toxoplasmosis pathwayJak2 , Stat3
tuberculosis pathwayJak2
type 2 diabetes mellitus pathwayIrs1 , Irs2 , Socs3
type II interferon signaling pathwayJak2 , Ptpn11 , Stat3
ubiquitin/proteasome degradation pathwaySocs3
vascular endothelial growth factor signaling pathwayPtpn11
Phenotype Annotations Associated with Genes in the leptin system pathway

References Associated with the leptin system pathway:

Ontology Path Diagram:

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Import into Pathway Studio: