LEPR (Leptin Receptor) Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the LEPR gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | LEPR |
|---|---|
| Full Name | Leptin receptor |
| Gene Type | Protein coding |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 3953 ncbi.nlm.nih.gov/gene/3953 |
| Ensembl ID | ENSG00000116678 |
| UniProt ID | P48357 |
| OMIM ID | 601007 |
| HGNC ID | 6554 |
| Aliases | CD295, LEP-R, OB-R, OBR |
Description
The LEPR gene encodes the leptin receptor, a single-pass type I membrane protein belonging to the class I cytokine receptor family. It is primarily expressed in the hypothalamus and other tissues, mediating the effects of leptin, an adipocyte-derived hormone that regulates energy balance, appetite, and body weight. Upon leptin binding, the receptor activates JAK/STAT signaling pathways, particularly STAT3, to modulate gene expression. Mutations in LEPR are associated with severe early-onset obesity and endocrine abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity, severe early-onset | Loss-of-function mutations impair leptin signaling, leading to hyperphagia and obesity. | ClinVar, OMIM |
| Leptin receptor deficiency | Homozygous or compound heterozygous mutations cause complete loss of receptor function. | OMIM, ClinVar |
| Hypogonadotropic hypogonadism | Impaired leptin signaling affects GnRH secretion, leading to reproductive dysfunction. | OMIM |
| Type 2 diabetes | Obesity-related insulin resistance is exacerbated by defective leptin signaling. | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Hypothalamus | High | High |
| Adipose tissue | Moderate | Medium |
| Pancreas | Low | Low |
| Muscle | Low | Low |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | Low | Hepatocellular carcinoma cell line |
| MCF7 | Low | Breast cancer cell line |
| SH-SY5Y | Moderate | Neuroblastoma cell line |
| Caco-2 | Low | Colorectal adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2380C>T (p.Arg794Ter) | Nonsense | Rare | Truncated receptor, loss of function |
| c.1673G>A (p.Trp558Ter) | Nonsense | Rare | Premature stop codon, loss of function |
| c.305C>T (p.Pro102Leu) | Missense | Rare | Impaired ligand binding |
| c.2262_2263del (p.Val755fs) | Frameshift | Rare | Frameshift leading to non-functional protein |
Mutation functional classification
Loss of Function (LOF)
Most LEPR mutations are loss-of-function, leading to impaired leptin binding or signal transduction, resulting in hyperphagia and obesity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for LEPR.
Dominant Negative (DN)
Some heterozygous mutations may exert dominant-negative effects by forming non-functional dimers with wild-type receptors.
View complete mutation data：
Gene Ontology (GO)
| • leptin receptor activity | • protein homodimerization activity |
| • signal transducer activity | • JAK-STAT cascade |
| • positive regulation of cell proliferation | • energy homeostasis |
Pathways
• Leptin signaling pathway
• JAK-STAT signaling pathway
• Cytokine-cytokine receptor interaction
• Neuroactive ligand-receptor interaction
Protein Summary
The leptin receptor (LEPR) is a 1165-amino acid glycoprotein with an extracellular domain containing cytokine receptor homology domains, a transmembrane domain, and an intracellular domain with conserved box1/box2 motifs for JAK binding. It exists in multiple isoforms (long, short, soluble) generated by alternative splicing. The long isoform (LEPRb) is essential for intracellular signaling via JAK2/STAT3, MAPK, and PI3K pathways. LEPR is critical for regulating food intake, energy expenditure, and neuroendocrine function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LEPR Knockout HEK293 Cell Line | EDJ-KQ507 | Human | 3953 | Details Get a Quote |
| LEPROTL1 Knockout HEK293 Cell Line | EDJ-KQ7355 | Human | 23484 | Details Get a Quote |
| LEPROT Knockout HEK293 Cell Line | EDJ-KQ12000 | Human | 54741 | Details Get a Quote |
| LEPR Knockout A-549 Cell Line | EDJ-KQ18828 | Human | 3953 | Details Get a Quote |
| LEPR Knockout HCT 116 Cell Line | EDJ-KQ18829 | Human | 3953 | Details Get a Quote |
| LEPR Knockout HeLa Cell Line | EDJ-KQ18830 | Human | 3953 | Details Get a Quote |
| LEPROTL1 Knockout A-549 Cell Line | EDJ-KQ33803 | Human | 23484 | Details Get a Quote |
| LEPROTL1 Knockout HCT 116 Cell Line | EDJ-KQ33804 | Human | 23484 | Details Get a Quote |
| LEPROTL1 Knockout HeLa Cell Line | EDJ-KQ33805 | Human | 23484 | Details Get a Quote |
| LEPROT Knockout A-549 Cell Line | EDJ-KQ40579 | Human | 54741 | Details Get a Quote |
| LEPROT Knockout HCT 116 Cell Line | EDJ-KQ40580 | Human | 54741 | Details Get a Quote |
| LEPROT Knockout HeLa Cell Line | EDJ-KQ40581 | Human | 54741 | Details Get a Quote |
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