LEP leptin [Homo sapiens (human)] - Gene

Summary

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Official Symbol: LEPprovided by HGNC
Official Full Name: leptinprovided by HGNC
Primary source: HGNC:6553
See related: Ensembl:ENSG00000174697; HPRD:01249; MIM:164160; Vega:OTTHUMG00000157564
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, and which plays a major role in the regulation of body weight. This protein, which acts through the leptin receptor, functions as part of a signaling pathway that can inhibit food intake and/or regulate energy expenditure to maintain constancy of the adipose mass. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis and wound healing. Mutations in this gene and/or its regulatory regions cause severe obesity, and morbid obesity with hypogonadism. This gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 7q31.3

Sequence :: Chromosome: 7; NC_000007.13 (127881331..127897682)

See LEP in Epigenomics, MapViewer

Chromosome 7 - NC_000007.13 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Intramedullary expression and bioactivity of leptin decreases significantly in patients with avascular necrosis of the femoral head.
Title: [Correlation between local microenvironment leptin expression and avascular necrosis of the femoral head].
Leptin accounted for 55 % of the relationship between V89L SRD5A2 polymorphism and alcohol craving in alcoholics.
Title: Association of V89L SRD5A2 polymorphism with craving and serum leptin levels in male alcohol addicts.
Under physiological conditions, leptin stimulates both ET-1 and NO activity in the human circulation.
Title: Leptin stimulates both endothelin-1 and nitric oxide activity in lean subjects but not in patients with obesity-related metabolic syndrome.
These results suggest that leptin acts as an important mediator linking obesity to elevated muscle sympathetic nerve activity and potentially to the development of hypertension.
Title: Experimental hyperleptinemia acutely increases vasoconstrictory sympathetic nerve activity in healthy humans.
Leptin concentration, at obesity level, variably increased natural killer cell metabolic activity and modulated NK cell cytotoxicity according to the target cells.
Title: Leptin modulates dose-dependently the metabolic and cytolytic activities of NK-92 cells.
Treatment of breast cancer cells with PPAR-gamma agonists elevated the expression of leptin and VEGF mRNA and protein, and increased cell viability and migration.
Title: Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.
The leptin adiponectin ratio remained predictive of incident cardiovascular disease (hazard ratio: 1.40 (95% CI 1.05-1.87), p=0.024).
Title: The plasma leptin/adiponectin ratio predicts first cardiovascular event in men: a prospective nested case-control study.
study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH
Title: Effects of estradiol and FSH on leptin levels in women with suppressed pituitary.
The induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by corticotropin-releasing hormone might promote fetal nutrient supply and placental corticosteroid metabolism in the phase before labour induction.
Title: Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts.
combination of in silico simulation and in vitro experiments was used to probe the role of the knotted topology introduced by the disulphide-bridge on leptin folding and function
Title: The unique cysteine knot regulates the pleotropic hormone leptin.

Submit: New GeneRIF Correction See all (850)

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

Obesity, severe, due to leptin deficiency

MIM: 614962

Genetic Testing Registry

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000221.1	NP_002106.1	HK3	BIND	PubMed	HKIII interacts with leptin. This interaction was modeled on a demonstrated interaction between rat HKIII and human leptin.
P41159	P01023	A2M	HPRD	PubMed
P41159	P10909	CLU	HPRD	PubMed
P41159	P02741	CRP	HPRD	PubMed
P41159	Q9UBU3	GHRL	HPRD	PubMed
P41159	P52790	HK3	HPRD	PubMed
P41159	P48357	LEPR	HPRD	PubMed
P41159	P54646	PRKAA2	HPRD	PubMed
P41159	O43699	SIGLEC6	HPRD	PubMed
P41159	P55089	UCN	HPRD	PubMed
BioGRID:110143	BioGRID:106524	A2M	BioGRID	PubMed	Reconstituted Complex
BioGRID:110143	BioGRID:107603	CLU	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110143	BioGRID:109348	HK3	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110143	BioGRID:112651	STAT3	BioGRID	PubMed	Reconstituted Complex

Pathways from BioSystems

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AMPK signaling, organism-specific biosystem (from WikiPathways)
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...
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...
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...
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
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...
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...
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...

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

Genotypes

See LEP SNP Geneview Report
See LEP SNP Genotype Report
See LEP SNP Variation Viewer Report

Homology

Homologs of the LEP gene: The LEP gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
growth factor activity	IEA Inferred from Electronic Annotation more info
hormone activity	IEA Inferred from Electronic Annotation more info
peptide hormone receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
adipose tissue development	IEA Inferred from Electronic Annotation more info
adult feeding behavior	ISS Inferred from Sequence or Structural Similarity more info
bile acid metabolic process	IEA Inferred from Electronic Annotation more info
bone mineralization involved in bone maturation	IEA Inferred from Electronic Annotation more info
cellular response to L-ascorbic acid	IEA Inferred from Electronic Annotation more info
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
eating behavior	IEA Inferred from Electronic Annotation more info
energy reserve metabolic process	IEA Inferred from Electronic Annotation more info
fatty acid catabolic process	IEA Inferred from Electronic Annotation more info
female pregnancy	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
leptin-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
leukocyte tethering or rolling	IEA Inferred from Electronic Annotation more info
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 cartilage development	IEA Inferred from Electronic Annotation more info
negative regulation of glucagon secretion	IEA Inferred from Electronic Annotation more info
negative regulation of glutamine transport	IEA Inferred from Electronic Annotation more info
negative regulation of transcription from RNA polymerase II promoter	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
placenta development	IDA Inferred from Direct Assay more info	PubMed
positive regulation of MAPK cascade	IEA Inferred from Electronic Annotation more info
positive regulation of STAT protein import into nucleus	IEA Inferred from Electronic Annotation more info
positive regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of cytokine production	IEA Inferred from Electronic Annotation more info
positive regulation of developmental growth	IDA Inferred from Direct Assay more info	PubMed
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 myeloid cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of tyrosine phosphorylation of Stat3 protein	IEA Inferred from Electronic Annotation more info
regulation of blood pressure	IEA Inferred from Electronic Annotation more info
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 steroid biosynthetic process	IEA Inferred from Electronic Annotation more info
response to dietary excess	IEA Inferred from Electronic Annotation more info
response to hypoxia	IEA Inferred from Electronic Annotation more info
response to insulin stimulus	IEA Inferred from Electronic Annotation more info
response to vitamin E	IEA Inferred from Electronic Annotation more info
tyrosine phosphorylation of STAT protein	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
extracellular region	TAS Traceable Author Statement more info
extracellular space	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: leptin

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

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.

Genomic

NG_007450.1 RefSeqGene

Range

5001..21352

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000230.2 → NP_000221.1 leptin precursor

Status: REVIEWED

Source sequence(s)

AC018635, BU752306, DA762132, U43653

Consensus CDS

CCDS5800.1

UniProtKB/TrEMBL

A4D0Y8

UniProtKB/Swiss-Prot

P41159

Related

ENSP00000312652, OTTHUMP00000212285, ENST00000308868, OTTHUMT00000349174

Conserved Domains (1) summary

pfam02024
Location:22 – 167
Blast Score: 708

Leptin; Leptin

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000007.13 Reference GRCh37.p10 Primary Assembly

Range

127881331..127897682

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000139.1 Alternate HuRef

Range

122242298..122258647

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CRA_TCAGchr7v2

Genomic

AC_000068.1 Alternate CRA_TCAGchr7v2

Range

127264455..127280803

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018918.1 Alternate CHM1_1.0

Range

131224516..131240864

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AACC02000001.1 (205655..222003)	None
genomic	ABBA01057678.1 (31772..48121)	None
genomic	AC018635.10 (34398..35973)	None
genomic	AC018662.3 (173369..173845)	None
genomic	AMYH01017915.1 (208167..224515)	None
genomic	AY996373.1	AAX81413.1
genomic	CH236947.1	EAL24315.1
genomic	CH471070.1	EAW83640.1
genomic	D63519.2	BAA09787.1
genomic	D63710.2	BAA09839.1
genomic	DQ054472.1	AAY46797.1
genomic	U43415.1	AAC31660.1
mRNA	AF008123.1	AAB63507.1
mRNA	AK313553.1	BAG36329.1
mRNA	BC060830.1	AAH60830.1
mRNA	BC069323.1	AAH69323.1
mRNA	BC069452.1	AAH69452.1
mRNA	BC069527.1	AAH69527.1
mRNA	BU752306.1	None
mRNA	D49487.1	BAA08448.1
mRNA	DA762132.1	None
mRNA	U18915.1	AAA60470.1
mRNA	U43653.1	AAC50400.1
other-genetic	HQ448411.1	ADQ32891.1