LEPR encodes leptin receptor (1,165 aa). Receptor for hormone LEP/leptin (Probable). Highest expression in Nerve Tibial (24.9 TPM) and Ovary (16.1 TPM).

Obesity due to leptin receptor gene deficiency is associated with mutations in the LEPR gene on chromosome 1.

LEPR is classified as a druggable target (Druggable Genome and External Side Of Plasma Membrane categories) with score 8.7.

Genetic testing for LEPR is available. Testing is considered confirmatory for diagnosis.

1 FDA-approved treatment is available for obesity due to leptin receptor gene deficiency, including SETMELANOTIDE (IMCIVREE, approved 2020). An additional 1 compound holds orphan drug designation.

Approved Therapies

Orphan Drug Designations

The following drugs have received orphan drug designation from the FDA for obesity due to leptin receptor gene deficiency. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Gene therapy approaches for obesity due to leptin receptor gene deficiency have been reported in the published literature.

Phenotype severity distribution: 7 always present features.

No clinical trials have been registered for obesity due to leptin receptor gene deficiency.

55 publications have been identified in PubMed for obesity due to leptin receptor gene deficiency. Research spans Basic Science / Preclinical (64%), Review / Meta-Analysis (13%), and Clinical Trial Publication (11%).

Recent Publications

• Ahima RS (2026). [PMID: 41043250](https://pubmed.ncbi.nlm.nih.gov/41043250/). *Annual review of physiology*. [Review / Meta-Analysis]

• Hegyi B (2026). [PMID: 41407304](https://pubmed.ncbi.nlm.nih.gov/41407304/). *American journal of physiology. Heart and circulatory physiology*. [Basic Science / Preclinical]

• Mira Hernandez J (2026). [PMID: 42168622](https://pubmed.ncbi.nlm.nih.gov/42168622/). *Basic Res Cardiol*. [Basic Science / Preclinical]

• Lytvyak E (2026). [PMID: 42068058](https://pubmed.ncbi.nlm.nih.gov/42068058/). *Obesity (Silver Spring)*. [Case Report / Case Series]

• Bittencourt JOA (2026). [PMID: 41412277](https://pubmed.ncbi.nlm.nih.gov/41412277/). *Life sciences*. [Basic Science / Preclinical]

• Janjua QM (2026). [PMID: 41826632](https://pubmed.ncbi.nlm.nih.gov/41826632/). *International journal of obesity (2005)*. [Gene Therapy / Novel Therapeutics]

• Yamane T (2026). [PMID: 41251330](https://pubmed.ncbi.nlm.nih.gov/41251330/). *Bioscience, biotechnology, and biochemistry*. [Basic Science / Preclinical]

• Chamarthi VS (2026). [PMID: 34424641](https://pubmed.ncbi.nlm.nih.gov/34424641/). *Unknown Journal*. [Review / Meta-Analysis]

• Aibara D (2026). [PMID: 41780810](https://pubmed.ncbi.nlm.nih.gov/41780810/). *Cell Signal*. [Basic Science / Preclinical]

• Tercan U (2026). [PMID: 41999616](https://pubmed.ncbi.nlm.nih.gov/41999616/). *Horm Res Paediatr*. [Case Report / Case Series]