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GenoLensGenoLens

LEPR

Chr 1p31.3

leptin receptor

Aliases:
OBR, CD295, LEP-R, OB-R
MANE:
ENST00000349533.11

Annotations refreshed 1 month ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • Hypogonadotropic hypogonadism (GMS)

    BIALLELIC, autosomal or pseudoautosomal
  • Severe early-onset obesity

    BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

  • obesity due to leptin receptor gene deficiency

    0.74
  • lipodystrophy

    0.54
  • type 2 diabetes mellitus

    0.51
  • obesity disorder

    0.43
  • diabetes mellitus

    0.43
  • Abnormality of the skeletal system

    0.41
  • familial partial lipodystrophy

    0.39
  • liver disorder

    0.37
  • Obesity

    0.36
  • generalized lipodystrophy

    0.36

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Leptin receptor

Receptor for hormone LEP/leptin (Probable) (PubMed:22405007). On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS. In the hypothalamus, LEP acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones (By similarity) (PubMed:9537324). In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic and affects innate and adaptive immunity (PubMed:12504075, PubMed:25060689, PubMed:8805376). Control of energy homeostasis and melanocortin production (stimulation of POMC and full repression of AgRP transcription) is mediated by STAT3 signaling, whereas distinct signals regulate NPY and the control of fertility, growth and glucose homeostasis. Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus. Has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T -ells. Leptin increases Th1 and suppresses Th2 cytokine production (By similarity)

Curated MONDO disease pages that list LEPR among their top associated genes.

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.