LEP leptin [Homo sapiens (human)] - Gene

Summary

Official Symbol: LEPprovided by HGNC
Official Full Name: leptinprovided by HGNC
Primary source: HGNC:HGNC:6553
See related: Ensembl:ENSG00000174697 MIM:164160
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: OB; OBS; LEPD
Summary: This gene encodes a protein that is secreted by white adipocytes into the circulation and plays a major role in the regulation of energy homeostasis. Circulating leptin binds to the leptin receptor in the brain, which activates downstream signaling pathways that inhibit feeding and promote energy expenditure. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation and wound healing. Mutations in this gene and its regulatory regions cause severe obesity and morbid obesity with hypogonadism in human patients. A mutation in this gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Aug 2017]
Expression: Restricted expression toward fat (RPKM 214.1) See more
Orthologs: mouse all

Genomic context

Location:: 7q32.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	7	NC_000007.14 (128241201..128257629)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (127881241..127897682)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

There was a strong correlation between maternal insulin and infant irisin levels in small for gestational age (SGA) infants, while in large for gestational age (LGA) Infants a strong correlation between infant insulin and leptin levels were found.
Title: The Role of Irisin, Insulin and Leptin in Maternal and Fetal Interaction
The authors concluded that a dysfunctional adipose tissue as suggested by a low adiponectin/leptin ratio may contribute to the increased oxidative stress and inflammation, hallmarks of the metabolic syndrome.
Title: Involvement of the leptin-adiponectin axis in inflammation and oxidative stress in the metabolic syndrome.
LEP 3'UTR A/C and LEPR K109R polymorphisms were associated with Leptin levels and obesity in Tunisian volunteers.
Title: Leptin and Leptin receptor polymorphisms, plasma Leptin levels and obesity in Tunisian volunteers.
in patients with coronary artery disease and without acute myocardial infarction leptin may represent a potential mechanism of adverse cardiac remodeling. Resistin and TNF-alpha might not be involved in ventricular remodeling in these patients.
Title: Plasma leptin, but not resistin, TNF-α and adiponectin, is associated with echocardiographic parameters of cardiac remodeling in patients with coronary artery disease.
Leptin modulates adventitial pericyte functions by autocrine and paracrine signaling.
Title: The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling.
Data suggest that, although changes in the plasma adiponectin/leptin ratio cannot explain improvements to glucose-insulin homeostasis indices following moderate-intensity aerobic training (16-week brisk walking program), a relationship with insulin sensitivity does exist in healthy women with obesity.
Title: The relationship between adiposopathy and glucose-insulin homeostasis is not affected by moderate-intensity aerobic training in healthy women with obesity.
Circulating leptin is associated with higher pro-neurotensin levels independent of diabetes, obesity and metabolic syndrome.
Title: Association between systemic leptin and neurotensin concentration in adult individuals with and without type 2 diabetes mellitus.
Serum level of leptin in prostate cancer.
Title: Circulating Levels of Omentin, Leptin, VEGF, and HGF and Their Clinical Relevance with PSA Marker in Prostate Cancer.
lean mass is an under recognized, but substantial, source of circulating leptin
Title: Associations between lean mass and leptin in men with chronic spinal cord injury: Results from the FRASCI-muscle study.
chemerin and leptin are elevated and omentin-1 and visfatin levels are decreased in Gestational diabetes mellitus women complicated by obesity.
Title: Circulating adipokines and mRNA expression in adipose tissue and the placenta in women with gestational diabetes mellitus.

Submit: New GeneRIF Correction See all GeneRIFs (1444)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Leptin deficiency or dysfunction MedGen: C3554224 OMIM: 614962 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association study identifies three novel loci for type 2 diabetes. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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AMP-activated Protein Kinase (AMPK) Signaling, organism-specific biosystem (from WikiPathways)
AMP-activated Protein Kinase (AMPK) Signaling, organism-specific biosystemAMPK signaling pathway, a fuel sensor and regulator, promotes ATP-producing and inhibits ATP-consuming pathways in various tissues. AMPK is a heterotrimer composed of alpha-catalytic and beta and gam...
AMPK signaling pathway, organism-specific biosystem (from KEGG)
AMPK signaling pathway, organism-specific biosystemAMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in th...
AMPK signaling pathway, conserved biosystem (from KEGG)
AMPK signaling pathway, conserved biosystemAMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in th...
Adipocytokine signaling pathway, organism-specific biosystem (from KEGG)
Adipocytokine signaling pathway, organism-specific biosystemIncreased 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...
Adipocytokine signaling pathway, conserved biosystem (from KEGG)
Adipocytokine signaling pathway, conserved biosystemIncreased 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...
Adipogenesis, organism-specific biosystem (from WikiPathways)
Adipogenesis, organism-specific biosystemThe different classess of factors involved in adipogenesis are shown. Adipogenesis is the process by which fat cells differentiate from predadipocytes to adipocytes (fat cells). Adipose tissue, compo...
Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines 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 ...
Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
Cytokine-cytokine receptor interaction, conserved biosystemCytokines 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 ...
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
Differentiation of white and brown adipocyte, organism-specific biosystem (from WikiPathways)
Differentiation of white and brown adipocyte, organism-specific biosystemDevelopment of white versus brown adipocytes (figure from Handbook of Obesity). Transcription factors and nuclear regulators controlling the development of white versus brown adipocytes are shown in ...
HIF-1-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
HIF-1-alpha transcription factor network, organism-specific biosystem
HIF-1-alpha transcription factor network
Incretin synthesis, secretion, and inactivation, organism-specific biosystem (from REACTOME)
Incretin synthesis, secretion, and inactivation, organism-specific biosystemIncretins are peptide hormones produced by the gut that enhance the ability of glucose to stimulate insulin secretion from beta cells in the pancreas. Two incretins have been identified: Glucagon-lik...
Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
Jak-STAT signaling pathway, organism-specific biosystemThe 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 homeost...
Jak-STAT signaling pathway, conserved biosystem (from KEGG)
Jak-STAT signaling pathway, conserved biosystemThe 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 homeost...
Leptin signaling pathway, organism-specific biosystem (from WikiPathways)
Leptin signaling pathway, organism-specific biosystemLeptin is a peptide hormone mainly synthesised and secreted from adipocytes. It is also expressed in other tissues including placenta, stomach and skeletal muscle. Leptin mediates its effects by bind...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
Neuroactive ligand-receptor interaction, organism-specific biosystem
Neuroactive ligand-receptor interaction
Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
Neuroactive ligand-receptor interaction, conserved biosystem
Neuroactive ligand-receptor interaction
Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystem (from KEGG)
Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
Non-alcoholic fatty liver disease (NAFLD), conserved biosystem (from KEGG)
Non-alcoholic fatty liver disease (NAFLD), conserved biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
Peptide hormone metabolism, organism-specific biosystem (from REACTOME)
Peptide hormone metabolism, organism-specific biosystemPeptide hormones are cleaved from larger precursors in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) of the cell. After secretion peptide hormones are modified and...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by Leptin, organism-specific biosystem (from REACTOME)
Signaling by Leptin, organism-specific biosystemLeptin (LEP, OB, OBS), a circulating adipokine, and its receptor LEPR (DB, OBR) control food intake and energy balance and are implicated in obesity-related diseases (recently reviewed in Amitani et ...
Signaling events mediated by PTP1B, organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by PTP1B, organism-specific biosystem
Signaling events mediated by PTP1B
Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...
Synthesis, secretion, and deacylation of Ghrelin, organism-specific biosystem (from REACTOME)
Synthesis, secretion, and deacylation of Ghrelin, organism-specific biosystemGhrelin is a peptide hormone of 28 amino acid residues which is acylated at the serine-3 of the mature peptide. Ghrelin is synthesized in several tissues: X/A-like cells of the gastric mucosa (the ma...
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1), organism-specific biosystem (from REACTOME)
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1), organism-specific biosystemIn L cells of the intestine the transcription factors TCF-4 (TCF7L2) and Beta-catenin form a heterodimer and bind the G2 enhancer of the Proglucagon gene GCG,activating its transcription to yield Pro...
Transcription factor regulation in adipogenesis, organism-specific biosystem (from WikiPathways)
Transcription factor regulation in adipogenesis, organism-specific biosystemThe transcription factors involved in adipogenesis are shown in the current pathway. Adipogensis is the biological proces of cell differentation in which preadipocytes are converted into adipocytes.
Transcriptional regulation of white adipocyte differentiation, organism-specific biosystem (from REACTOME)
Transcriptional regulation of white adipocyte differentiation, organism-specific biosystemAdipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. During this process the preadipocytes cease to proliferate, begin to accumulate lipid droplets and develo...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

RH70631 (e-PCR)
- UniSTS:78152

LEP-3 (e-PCR)
- UniSTS:253879

OBS (e-PCR)
- UniSTS:35280

STS-U43653 (e-PCR)
- UniSTS:35281

NoName (e-PCR)
- UniSTS:481242

Homology

Homologs of the LEP gene: The LEP gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and frog.
Orthologs from Annotation Pipeline: 143 organisms have orthologs with human gene LEP
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
hormone activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
peptide hormone receptor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
activation of protein kinase C activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
activation of protein kinase C activity	IDA Inferred from Direct Assay more info	PubMed
adipose tissue development	IEA Inferred from Electronic Annotation more info
adult feeding behavior	ISS Inferred from Sequence or Structural Similarity more info
angiogenesis	IDA Inferred from Direct Assay more info	PubMed
aorta development	IEA Inferred from Electronic Annotation more info
bile acid metabolic process	IEA Inferred from Electronic Annotation more info
bone growth	ISS Inferred from Sequence or Structural Similarity more info
bone mineralization involved in bone maturation	IEA Inferred from Electronic Annotation more info
cardiac muscle hypertrophy	IEA Inferred from Electronic Annotation more info
cellular response to L-ascorbic acid	IEA Inferred from Electronic Annotation more info
cellular response to leptin stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to retinoic acid	IEA Inferred from Electronic Annotation more info
central nervous system neuron development	IEA Inferred from Electronic Annotation more info
cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
circadian rhythm	IEA Inferred from Electronic Annotation more info
determination of adult lifespan	IEA Inferred from Electronic Annotation more info
eating behavior	IEA Inferred from Electronic Annotation more info
elastin metabolic process	IEA Inferred from Electronic Annotation more info
energy reserve metabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
fatty acid beta-oxidation	IEA Inferred from Electronic Annotation more info
female pregnancy	IEA Inferred from Electronic Annotation more info
glucose homeostasis	IEA Inferred from Electronic Annotation more info
glucose metabolic process	IEA Inferred from Electronic Annotation more info
glycerol biosynthetic process	IEA Inferred from Electronic Annotation more info
hormone metabolic process	IEA Inferred from Electronic Annotation more info
insulin secretion	IEA Inferred from Electronic Annotation more info
interleukin-12 production	IEA Inferred from Electronic Annotation more info
interleukin-6 secretion	IDA Inferred from Direct Assay more info	PubMed
interleukin-8 secretion	IDA Inferred from Direct Assay more info	PubMed
intestinal absorption	IDA Inferred from Direct Assay more info	PubMed
intracellular signal transduction	IEA Inferred from Electronic Annotation more info
leptin-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
leukocyte tethering or rolling	IEA Inferred from Electronic Annotation more info
lipid metabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
negative regulation of appetite	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of appetite by leptin-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of appetite by leptin-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of autophagy	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cartilage development	IEA Inferred from Electronic Annotation more info
negative regulation of glucagon secretion	IEA Inferred from Electronic Annotation more info
negative regulation of glucose import	IDA Inferred from Direct Assay more info	PubMed
negative regulation of glutamine transport	IEA Inferred from Electronic Annotation more info
negative regulation of lipid storage	IEA Inferred from Electronic Annotation more info
negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
negative regulation of vasoconstriction	IEA Inferred from Electronic Annotation more info
ovulation from ovarian follicle	IEA Inferred from Electronic Annotation more info
phagocytosis	IEA Inferred from Electronic Annotation more info
placenta development	IDA Inferred from Direct Assay more info	PubMed
positive regulation of JAK-STAT cascade	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of JAK-STAT cascade	IDA Inferred from Direct Assay more info	PubMed
positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
positive regulation of MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of TOR signaling	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
positive regulation of developmental growth	IDA Inferred from Direct Assay more info	PubMed
positive regulation of fat cell apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of follicle-stimulating hormone secretion	IEA Inferred from Electronic Annotation more info
positive regulation of hepatic stellate cell activation	IEA Inferred from Electronic Annotation more info
positive regulation of insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of ion transport	IEA Inferred from Electronic Annotation more info
positive regulation of luteinizing hormone secretion	IEA Inferred from Electronic Annotation more info
positive regulation of p38MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of p38MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
positive regulation of peroxisome proliferator activated receptor signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of phosphatidylinositol 3-kinase signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of phosphatidylinositol 3-kinase signaling	IDA Inferred from Direct Assay more info	PubMed
positive regulation of phosphatidylinositol 3-kinase signaling	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein import into nucleus	IEA Inferred from Electronic Annotation more info
positive regulation of protein kinase B signaling	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of reactive oxygen species metabolic process	IEA Inferred from Electronic Annotation more info
positive regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
positive regulation of tyrosine phosphorylation of STAT protein	IEA Inferred from Electronic Annotation more info
prostaglandin secretion	IDA Inferred from Direct Assay more info	PubMed
regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
regulation of blood pressure	IEA Inferred from Electronic Annotation more info
regulation of bone remodeling	ISS Inferred from Sequence or Structural Similarity more info
regulation of brown fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
regulation of cell cycle	IDA Inferred from Direct Assay more info	PubMed
regulation of cytokine production involved in inflammatory response	IDA Inferred from Direct Assay more info	PubMed
regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
regulation of gluconeogenesis	IEA Inferred from Electronic Annotation more info
regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
regulation of intestinal cholesterol absorption	IEA Inferred from Electronic Annotation more info
regulation of lipoprotein lipid oxidation	IEA Inferred from Electronic Annotation more info
regulation of natural killer cell activation	IDA Inferred from Direct Assay more info	PubMed
regulation of natural killer cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
regulation of natural killer cell proliferation	IDA Inferred from Direct Assay more info	PubMed
regulation of nitric-oxide synthase activity	IDA Inferred from Direct Assay more info	PubMed
regulation of signaling receptor activity	IEA Inferred from Electronic Annotation more info
regulation of steroid biosynthetic process	IEA Inferred from Electronic Annotation more info
response to activity	IEA Inferred from Electronic Annotation more info
response to dietary excess	IEA Inferred from Electronic Annotation more info
response to estradiol	IEA Inferred from Electronic Annotation more info
response to ethanol	IEA Inferred from Electronic Annotation more info
response to hypoxia	IEA Inferred from Electronic Annotation more info
response to insulin	IBA Inferred from Biological aspect of Ancestor more info	PubMed
response to vitamin E	IEA Inferred from Electronic Annotation more info
sexual reproduction	IMP Inferred from Mutant Phenotype more info	PubMed
tyrosine phosphorylation of STAT protein	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
extracellular region	TAS Traceable Author Statement more info
extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extracellular space	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: leptin

Names: leptin (murine obesity homolog); leptin (obesity homolog, mouse); obese protein; obese, mouse, homolog of; obesity factor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.