LEPR across dismech

LEPR (leptin receptor) is named by 2 disorder entries.

How the entries record the gene

Both entries that name LEPR type it as causative (Obesity; and Obesity Due to MC4R Pathway Disruption), and both record the variants as germline (Obesity; and Obesity Due to MC4R Pathway Disruption). No entry naming LEPR leaves its genetic record untyped (0), and none names the gene without a genetic record (0).

ClinGen's gene-disease validity table classifies LEPR for 0 diseases, so the typing here rests on the entries' own cited evidence rather than on an external classification.

Where the gene sits in the pathographs

The two entries place LEPR on one node each: MC4R pathway signaling failure in the monogenic/melanocortin entry, and Hypothalamic Dysregulation in the broader obesity entry — the same mechanism named at two levels of resolution. The processes carried by the nodes that name LEPR are adenylate cyclase-activating G protein-coupled receptor signaling pathway; and feeding behavior, which is the melanocortin arm downstream of the receptor rather than the receptor step itself; the receptor's own activity is recorded on the melanocortin node as a decreased molecular function.

No node naming LEPR declares conformance to a mechanism module (0), and no treatment record in the KB names the gene (0) — although both entries describe setmelanotide, which acts downstream at MC4R rather than on the receptor this gene encodes.

Normal function

The ai-gene-review ingest layer currently reports 0 core function terms for LEPR, because the ingest tables are pinned to an ai-gene-review commit that predates the review of this gene. The upstream review was written in the same round of work as this page and gives leptin receptor activity at the plasma membrane, the leptin-mediated signalling pathway through STAT, and hypothalamic regulation of feeding behaviour and energy homeostasis as the gene's core functions; those terms will appear here once the ingest pin is advanced. Until then the function layer and the KB layer share 0 GO terms, which reflects the pin rather than a disagreement.