LEPR (Leptin receptor) variants and mutations

LEPR (also known as Leptin receptor) is a human protein-coding gene encoding a leptin receptor protein. It transmits leptin signals to hypothalamic circuits that regulate appetite, body weight, endocrine axes, and energy expenditure. Biallelic loss-of-function variants cause severe early-onset obesity with intense hyperphagia and frequently hypogonadotropic hypogonadism. This analysis covers 1,511 LEPR variants and mutations. Of these, 69% have computational variant effect predictions. Disease context includes obesity due to leptin receptor gene deficiency, lipodystrophy, and type 2 diabetes mellitus. Example LEPR variants include M1?, I2T, and I2V.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable LEPR variants

Examples include M1?, I2T, I2V, C3S, C3C, Q4H, Q4Q, K5N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.