LEP

HIGH

Leptin

Chromosome: 7q32.1

Gene Overview

LEP encodes leptin, an adipokine secreted by adipose tissue that signals energy sufficiency to the hypothalamus via the leptin receptor (LEPR). Leptin suppresses appetite and promotes energy expenditure through melanocortin and other pathways. Rare LEP mutations cause severe early-onset obesity; common variants contribute to polygenic obesity. Circulating leptin correlates with fat mass; diet and physical activity modulate levels. Leptin resistance in obesity is a therapeutic target.

Molecular Function

hormone activity
appetite regulation
energy homeostasis

Protein class: cytokine

Regulatory Annotation

Promoter activity: Expressed in adipocytes; regulated by insulin and glucocorticoids.

eQTL tissues: adipose tissue, subcutaneous fat

Tissue Expression Context

adipose tissueTPM range: 50-300GTEx vv8

Pathways

insulin-signaling

Linked Diseases & Exposures

Diseases

obesity— Mendelian and GWAS, strength 0.9
type-2-diabetes— pathway, strength 0.7

Exposures

obesity-exposure— literature, strength 0.85
diet-quality— literature, strength 0.75

Mechanistic Hypotheses

Leptin–melanocortin axis defects (LEP, LEPR, POMC, MC4R) cause monogenic or severe obesity; common variants add to polygenic risk; diet and activity modulate leptin sensitivity.

Mendelian genetics; GWAS; intervention studies.

HIGH

Confidence Rating

Overall evidence confidence for this gene entry: HIGH

References

1.Friedman JM (2019). Leptin and the regulation of body weight. Nature Medicine. doi:10.1038/s41591-018-0307-4