Gene Report

Basic Information

Approved Symbol	LEPR
Approved Name	leptin receptor
Symbol Alias	OBR, CD295
Location	1p31
Position	chr1:65886335-66103176 (+)
External Links	Entrez Gene: 3953 Ensembl: ENSG00000116678 UCSC: uc001dci.3 HGNC ID: 6554
No. of Studies (Positive/Negative)	3(3/0)
Type	Literature-origin; SNP mapped; Protein mapped

Positive relationships between LEPR and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
LEPR	Sequeira, 2007	patients and normal controls		Selected differentially expressed genes in hippocampus Selected differentially expressed genes in hippocampus
LEPR	Klempan, 2009	patients and normal controls		Selected differentially expressed genes in BA44 to BA47 (ANO...... Selected differentially expressed genes in BA44 to BA47 (ANOVA and t-test P < 0.01, fold change 1.3t) More...

Positive relationships between LEPR and other components at different levels (count: 2)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Relation Description
Name in Literature	Related Components
LEPR		Hippocampus(hippocampus)	brain morphology and function	Sequeira, 2007	patients and normal controls	Selected differentially expressed genes in hippocampus Selected differentially expressed genes in hippocampus
leptin receptor (LEPR)		Suicide(suicide attempt)	symptoms	Lalovic, 2010	patients and normal controls	Fatty acid desaturase (FADS1), leptin receptor (LEPR), phosp...... Fatty acid desaturase (FADS1), leptin receptor (LEPR), phosphoinositide-3-kinase (class 2 alpha; PIK3C2A) and stearoyl-CoA desaturase (SCD) were consistently down-regulated in all three regions of the frontal cortex of depressed suicides compared to comparison subjects More...

Positive relationship network of LEPR in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between LEPR and MDD (count: 0)

Negative relationships between LEPR and other components at different levels (count: 0)

LEPR related SNPs in MK4MDD (count: 1)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs3806318	chr1:65885357(Forward)	downstream_gene_variant; upstream_gene_variant	1(1/0)

LEPR related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Leptin receptor	P48357	1(1/0)	Literature-origin

LEPR related GO terms (count: 11)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0008203	cholesterol metabolic process	biological process	IEA
GO:0004888	transmembrane signaling receptor activity	molecular function	TAS[9537324]
GO:0007275	multicellular organismal development	biological process	TAS[9537324]
GO:0051346	negative regulation of hydrolase activity	biological process	IEA
GO:0005576	extracellular region	cellular component	IEA
GO:0007166	cell surface receptor signaling pathway	biological process	TAS[9537324]
GO:0004896	cytokine receptor activity	molecular function	IEA
GO:0016021	integral to membrane	cellular component	IEA
GO:0005515	protein binding	molecular function	IPI[17474147]
GO:0006112	energy reserve metabolic process	biological process	TAS[9537324]
GO:0005886	plasma membrane	cellular component	IEA

LEPR related KEGG pathways (count: 4)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04630	jak stat_signaling_pathway	Jak-STAT signaling pathway	The Janus kinase/signal transducers and activators of transc...... The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in animals, from humans to flies. In mammals, the JAK/STAT pathway is the principal signaling mechanism for a wide array of cytokines and growth factors. Following the binding of cytokines to their cognate receptor, STATs are activated by members of the JAK family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. In addition to the activation of STATs, JAKs mediate the recruitment of other molecules such as the MAP kinases, PI3 kinase etc. These molecules process downstream signals via the Ras-Raf-MAP kinase and PI3 kinase pathways which results in the activation of additional transcription factors. More...
hsa04920	adipocytokine signaling_pathway	Adipocytokine signaling pathway	Increased adipocyte volume and number are positively correla...... Increased adipocyte volume and number are positively correlated with leptin production, and negatively correlated with production of adiponectin. Leptin is an important regulator of energy intake and metabolic rate primarily by acting at hypothalamic nuclei. Leptin exerts its anorectic effects by modulating the levels of neuropeptides such as NPY, AGRP, and alpha-MSH. This leptin action is through the JAK kinase, STAT3 phosphorylation, and nuclear transcriptional effect. Adiponectin lowers plasma glucose and FFAs. These effects are partly accounted for by adiponectin-induced AMPK activation, which in turn stimulates skeletal muscle fatty acid oxidation and glucose uptake. Furthermore, activation of AMPK by adiponectin suppresses endogenous glucose production, concomitantly with inhibition of PEPCK and G6Pase expression. The proinflammatory cytokine TNFalpha has been implicated as a link between obesity and insulin resistance. TNFalpha interferes with early steps of insulin signaling. Several data have shown that TNFalpha inhibits IRS1 tyrosine phosphorylation by promoting its serine phosphorylation. Among the serine/threonine kinases activated by TNFalpha, JNK, mTOR and IKK have been shown to be involved in this phosphorylation. More...
hsa04080	neuroactive ligand_receptor_interaction	Neuroactive ligand-receptor interaction
hsa04060	cytokine cytokine_receptor_interaction	Cytokine-cytokine receptor interaction	Cytokines are soluble extracellular proteins or glycoprotein...... Cytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell growth, differentiation, cell death, angiogenesis, and development and repair processes aimed at the restoration of homeostasis. Cytokines are released by various cells in the body, usually in response to an activating stimulus, and they induce responses through binding to specific receptors on the cell surface of target cells. Cytokines can be grouped by structure into different families and their receptors can likewise be grouped. More...

LEPR related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
LEPTIN_PATHWAY	leptin pathway	Reversal of Insulin Resistance by Leptin	The insulin resistance of type II diabetes appears to be cau...... The insulin resistance of type II diabetes appears to be caused in part by the presence of high levels of lipids in cells such as skeletal muscle where this would not normally be found. The presence of excess lipid stores in skeletal muscle cells interferes with energy metabolism, impairing glucose oxidation and insulin response. Skeletal muscle is one of the primary glucose-consuming tissues, giving it a central role in insulin resistance. The increased risk of diabetes associated with obesity may be caused by increased lipid deposits in skeletal muscle and liver, creating insulin resistance. Leptin is a peptide hormone secreted by adipose tissue that has been associated with many processes. One of the target tissues of leptin is the hypothalamus where it can act to regulate feeding behavior and metabolism. Another leptin target is skeletal muscle. Activation of leptin signaling in skeletal muscle activates the AMP-activated protein kinase (AMP-kinase), known to play a key role in signaling in response to nutrients throughout evolution. AMPK phosphorylates and inactivates the enzyme ACC, acetyl-CoA carboxylase. ACC catalyzes the production of malonyl-CoA from acetyl-CoA. Malonyl-CoA in turn is an inhibitor of the import of fatty acids into mitochondria by carnitine palmitoyl-transferase I for oxidation and energy production. In the presence of leptin, AMPK is activated, ACC is inhibited, and malonyl-CoA levels fall, increasing the oxidation of fatty acids and reducing the lipid content of cells. The reduced lipid content in skeletal muscle allows insulin signaling and glucose consumption to return to their normal levels, reducing insulin resistance. More...

LEPR related Reactome pathways (count: 0)

LEPR related interactors from protein-protein interaction data in HPRD (count: 14)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
LEPR	DGKZ	No	in vitro;in vivo;yeast 2-hybrid	11078732
LEPR	APOD	Yes	in vitro;in vivo;yeast 2-hybrid	11344130
LEPR	SNX6	No	in vitro;in vivo	11279102
LEPR	CLU	No	in vitro	12824284
LEPR	PTPN11	No	in vivo	11018044
LEPR	SNX1	No	in vivo	9819414
LEPR	SNX4	No	in vivo	9819414
LEPR	SNX2	No	in vitro;in vivo	9819414
LEPR	JAK2	No	in vitro	8608603
LEPR	STAT3	No	in vivo	8608603
LEPR	LEP	No	in vivo	8608603
LEPR	PIN1	No	yeast 2-hybrid	16169070
LEPR	LEPR	Yes	in vivo	15771593
LEPR	SOCS3	No	in vitro;in vivo	11018044

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways