LEP Gene

Name	leptin
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Leptin is an adipocyte‐derived hormone with multifaceted roles in metabolic regulation. It is critically involved in controlling food intake, energy expenditure, and neuroendocrine function, in part by stimulating fatty acid oxidation in peripheral tissues such as skeletal muscle through activation of AMPK‐dependent pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In leptin-deficient individuals, replacement therapy not only reduces hyperphagia and fat mass but also improves endocrine and immune functions, underscoring leptin’s systemic regulatory capacity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the brain, leptin acts on hypothalamic circuits that control energy homeostasis. It is essential during a neonatal critical period for the proper formation of arcuate nucleus projections, and in the adult, leptin’s action on specific neuronal populations – particularly by modulating inhibitory (GABAergic) neurons to relieve suppression of anorexigenic pro-opiomelanocortin (POMC) neurons – is central to its anti-obesity effects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Leptin also regulates lipid metabolism in the liver by repressing key enzymes such as stearoyl-CoA desaturase-1 (SCD-1), thereby contributing to improved lipid profiles and overall metabolic balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, leptin signals via pathways involving Jak2 and STAT3. Its signaling is tightly regulated by phosphatases such as PTP1B, which dephosphorylates leptin receptor-associated kinases, and mutations in leptin receptor signaling domains further highlight the hormone’s role in modulating energy homeostasis and other metabolic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies demonstrate that leptin acts both centrally and peripherally to integrate nutritional signals with neuroendocrine and metabolic responses. Such a broad range of activities underscores leptin’s therapeutic potential in the management of obesity and its related metabolic disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yasuhiko Minokoshi, Young-Bum Kim, Odile D Peroni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/415339a"}], "href": "https://doi.org/10.1038/415339a"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11797013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11797013"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "I Sadaf Farooqi, Giuseppe Matarese, Graham M Lord, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI15693"}], "href": "https://doi.org/10.1172/JCI15693"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12393845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12393845"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sebastien G Bouret, Shin J Draper, Richard B Simerly "}, {"type": "b", "children": [{"type": "t", "text": "Trophic action of leptin on hypothalamic neurons that regulate feeding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1095004"}], "href": "https://doi.org/10.1126/science.1095004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15064420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15064420"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Linh Vong, Chianping Ye, Zongfang Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2011.05.028"}], "href": "https://doi.org/10.1016/j.neuron.2011.05.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21745644"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21745644"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shirly Pinto, Aaron G Roseberry, Hongyan Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rapid rewiring of arcuate nucleus feeding circuits by leptin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1089459"}], "href": "https://doi.org/10.1126/science.1089459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15064421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15064421"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Paul Cohen, Makoto Miyazaki, Nicholas D Socci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1071527"}], "href": "https://doi.org/10.1126/science.1071527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12114623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12114623"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Janice M Zabolotny, Kendra K Bence-Hanulec, Alain Stricker-Krongrad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTP1B regulates leptin signal transduction in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1534-5807(02)00148-x"}], "href": "https://doi.org/10.1016/s1534-5807(02"}, {"type": "t", "text": "00148-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11970898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11970898"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sarah H Bates, Walter H Stearns, Trevor A Dundon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STAT3 signalling is required for leptin regulation of energy balance but not reproduction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01388"}], "href": "https://doi.org/10.1038/nature01388"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12594516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12594516"}]}]}]}
Synonyms	LEPD, OBS
Proteins	LEP_HUMAN
NCBI Gene ID	3952
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LEP has 13,790 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 114 datasets.

Click the + buttons to view associations for LEP from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LEP Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by LEP gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of LEP gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of LEP gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of LEP gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LEP gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving LEP protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of LEP gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LEP gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LEP gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of LEP gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LEP gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of LEP gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LEP gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LEP gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LEP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of LEP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with LEP gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with LEP gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of LEP gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LEP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LEP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with LEP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of LEP gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LEP gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LEP gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LEP gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LEP gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving LEP gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving LEP gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LEP gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with LEP gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with LEP gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with LEP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LEP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at LEP gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LEP gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LEP gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing LEP from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with LEP gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with LEP gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.