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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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LEP
leptin
Chromosome 7 Β· 7q32.1
NCBI Gene: 3952Ensembl: ENSG00000174697.6HGNC: HGNC:6553UniProt: A4D0Y8
1,912PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cellular response to leptin stimulusnegative regulation of autophagyplacenta developmentprostaglandin secretionobesity due to congenital leptin deficiencytype 2 diabetes mellituseye diseasepeptic ulcer disease
✦AI Summary

Leptin (LEP) is a 16-kDa adipokine that functions as a master regulator of energy homeostasis and body weight control 1. Upon secretion by adipocytes in proportion to total adipose tissue mass, leptin circulates systemically and binds to leptin receptors (LEPR) throughout the body to activate multiple signaling cascades 234. In the hypothalamus, leptin acts as a central appetite suppressant by activating anorexigenic POMC neurons and inhibiting orexigenic NPY neurons, thereby decreasing food intake and increasing energy expenditure 5. Peripherally, leptin regulates glucose homeostasis by reducing intestinal glucose absorption through PKC-dependent signaling, influences pancreatic beta-cell function and insulin secretion, and modulates reproductive processes 6. Leptin also exhibits pro-inflammatory and immune-modulatory roles, enhancing neutrophil chemotaxis, macrophage phagocytosis, and promoting T-cell proliferation toward Th1 responses through JAK2-STAT3 pathway activation 27. A negative feedback regulatory loop exists whereby leptin suppresses adipocyte TET2 levels via JAK2-STAT3 signaling, while TET2 reciprocally promotes leptin gene expression, providing compensatory metabolic control during obesity 8. Mutations or deficiency in LEP impair energy homeostasis, predisposing to obesity and type-2 diabetes 9.

Sources cited
1
Leptin activates major signaling pathways by binding LEPR and induces pro-inflammatory effects via JAK2-STAT3 pathway
PMID: 15899045
2
Leptin acts as a growth factor activating JAK2-STAT3 and MAPK/PI3K-AKT1 pathways to regulate cell cycle genes
PMID: 17344214
3
Leptin has multiple peripheral effects on metabolism, immunity, and pro-inflammatory signaling via JAK2-PI3K-MAP2K1-MAPK14 pathways
PMID: 19688109
4
Leptin regulates bone mass, reproduction, beta-cell function, and exhibits pro-angiogenic effects on endothelial cells
PMID: 11460888
5
Leptin reduces intestinal glucose absorption by enterocytes through PKC-dependent activation of p38, PI3K, and ERK signaling
PMID: 24340098
6
Leptin promotes CD4+ T-cell proliferation and reduces autophagy through MTOR pathway activation and BCL2 up-regulation
PMID: 25060689
7
Leptin suppresses adipocyte TET2 via JAK2-STAT3 signaling; TET2 increases leptin expression, forming a negative feedback regulatory loop
PMID: 38561362
8
Leptin is a 16-kDa adipokine secreted by adipocytes that controls food intake, energy homeostasis, immune response, and reproduction
PMID: 34944480
9
Leptin mutations decrease leptin concentration and increase obesity and type-2 diabetes; leptin controls appetite through hypothalamic effects
PMID: 28436331
Disease Associationsβ“˜21
obesity due to congenital leptin deficiencyOpen Targets
0.72Strong
type 2 diabetes mellitusOpen Targets
0.50Moderate
eye diseaseOpen Targets
0.31Weak
peptic ulcer diseaseOpen Targets
0.31Weak
gastric ulcerOpen Targets
0.31Weak
duodenal ulcerOpen Targets
0.31Weak
spondylolisthesisOpen Targets
0.30Weak
inherited obesityOpen Targets
0.21Weak
obesityOpen Targets
0.14Weak
metabolic syndromeOpen Targets
0.14Weak
polycystic ovary syndromeOpen Targets
0.13Weak
hepatocellular carcinomaOpen Targets
0.12Weak
breast cancerOpen Targets
0.12Weak
type 1 diabetes mellitusOpen Targets
0.12Weak
rheumatoid arthritisOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
Alzheimer diseaseOpen Targets
0.12Weak
systemic lupus erythematosusOpen Targets
0.12Weak
cancerOpen Targets
0.12Weak
chronic kidney diseaseOpen Targets
0.11Weak
Leptin deficiencyUniProt
Pathogenic Variants8
NM_000230.3(LEP):c.398del (p.Gly133fs)Pathogenic
Obesity due to congenital leptin deficiency|not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 133
NM_000230.3(LEP):c.309C>A (p.Asn103Lys)Likely pathogenic
not provided|LEP-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 103
NM_000230.3(LEP):c.190C>T (p.Pro64Ser)Pathogenic
Leptin dysfunction|Obesity due to congenital leptin deficiency
β˜…β˜†β˜†β˜†2023β†’ Residue 64
NM_000230.3(LEP):c.175G>A (p.Gly59Ser)Pathogenic
Leptin dysfunction|Obesity due to congenital leptin deficiency
β˜…β˜†β˜†β˜†2023β†’ Residue 59
NM_000230.3(LEP):c.73C>T (p.Gln25Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 25
NM_000230.3(LEP):c.461T>C (p.Leu154Pro)Likely pathogenic
Obesity due to congenital leptin deficiency
β˜…β˜†β˜†β˜†2017β†’ Residue 154
NM_000230.3(LEP):c.298G>T (p.Asp100Tyr)Pathogenic
Leptin dysfunction
β˜†β˜†β˜†β˜†2015β†’ Residue 100
NM_000230.3(LEP):c.313C>T (p.Arg105Trp)Pathogenic
Obesity due to congenital leptin deficiency
β˜†β˜†β˜†β˜†2004β†’ Residue 105
View on ClinVar β†—
Related Genes
THPOProtein interaction98%ADIPOQProtein interaction97%SIGLEC6Protein interaction96%CSF3Protein interaction95%CSH1Protein interaction95%GH2Protein interaction95%
Tissue Expression6 tissues
Heart
100%
Lung
19%
Ovary
12%
Liver
11%
Brain
7%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
LEPTHPOADIPOQSIGLEC6CSF3CSH1GH2
PROTEIN STRUCTURE
Preparing viewer…
PDB1AX8 Β· 2.40 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.14LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.65 [0.39–1.14]
RankingsWhere LEP stands among ~20K protein-coding genes
  • #59of 20,598
    Most Researched1,912 Β· top 1%
  • #3,009of 5,498
    Most Pathogenic Variants8
  • #11,809of 17,882
    Most Constrained (LOEUF)1.14
Genes detectedLEP
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
The impact of medical interpreter services on the quality of health care: a systematic review.
PMID: 15894705
Med Care Res Rev Β· 2005
1.00
2
Promoter Methylation of
PMID: 33530087
Obes Facts Β· 2021
0.92
3
A negative feedback loop between TET2 and leptin in adipocyte regulates body weight.
PMID: 38561362
Nat Commun Β· 2024
0.90
4
Associations of
PMID: 30935050
Nutrients Β· 2019
0.80
5
Raised Leptin and Pappalysin2 cell-free RNAs are the hallmarks of pregnancies complicated by preeclampsia with fetal growth restriction.
PMID: 40681537
Nat Commun Β· 2025
0.78