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This gene encodes a protein that is secreted by white adipocytes into the circulation and plays a major role in the regulation of energy homeostasis. Circulating leptin binds to the leptin receptor in the brain, which activates downstream signaling pathways that inhibit feeding and promote energy expenditure. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation and wound healing. Mutations in this gene and its regulatory regions cause severe obesity and morbid obesity with hypogonadism in human patients. A mutation in this gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Aug 2017]
LEP (Leptin) is a Protein Coding gene. Diseases associated with LEP include Leptin Deficiency Or Dysfunction and Eating Disorder. Among its related pathways are Signaling by GPCR and PEDF Induced Signaling. Gene Ontology (GO) annotations related to this gene include growth factor activity and peptide hormone receptor binding.
Leptin was initially thought to have a role in energy homeostasis and obesity. It acts via leptin receptors (Ob-Rs), which are transmembrane catalytic receptors found on NPY/AgRP and alpha-MSH/CART neurons in hypothalamic nuclei. There are six isoforms of Ob-R.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0003677 | DNA binding | IEA | -- |
GO:0005102 | signaling receptor binding | IEA | -- |
GO:0005179 | hormone activity | IBA | 21873635 |
GO:0051428 | peptide hormone receptor binding | IBA | 21873635 |
GO:1990460 | leptin receptor binding | IDA | 27037668 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | TAS | -- |
GO:0005615 | extracellular space | ISS | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005829 | cytosol | ISS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | AMP-activated Protein Kinase (AMPK) Signaling | ||
2 | Incretin synthesis, secretion, and inactivation | ||
3 | Peptide hormone metabolism | ||
4 | Adipocytokine signaling pathway | ||
5 | PEDF Induced Signaling |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000122 | negative regulation of transcription by RNA polymerase II | IEA | -- |
GO:0001525 | angiogenesis | IDA | 19910644 |
GO:0001542 | ovulation from ovarian follicle | IEA | -- |
GO:0001666 | response to hypoxia | IEA | -- |
GO:0001819 | positive regulation of cytokine production | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Olanzapine | Approved, Investigational | Pharma | Antagonist, Agonist, Full agonist, Inverse agonist | 442 | ||
Risperidone | Approved, Investigational | Pharma | Antagonist, Inverse agonist | SR-2A inhibitor | 532 | |
Androstenedione | Experimental, Illicit | Pharma | 0 | |||
LEP (116-130) (mouse) | Pharma | An antiobesity hormone, Synthetic leptin peptide fragment | 0 | |||
antipsychotics | Pharma | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
Compound | Action | Cas Number |
---|---|---|
LEP (116-130) (mouse) | Synthetic leptin peptide fragment | 258276-95-8 |
Compound | Action | Cas Number |
---|---|---|
LEP (116-130) (mouse) | An antiobesity hormone | 258276-95-8 |
ExUns: | 1a | · | 1b | ^ | 2a | · | 2b |
---|---|---|---|---|---|---|---|
SP1: | |||||||
SP2: |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | LEP 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | LEP 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | LEP 30 |
|
||
OB 31 |
|
OneToOne | |||
Rat (Rattus norvegicus) |
Mammalia | Lep 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Lep 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | LEP 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | LEP 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100486715 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | lepa 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 07 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
724209 | Conflicting Interpretations: Leptin deficiency or dysfunction; not provided | 128,254,424(+) | G/A | SYNONYMOUS_VARIANT | |
741430 | Likely Benign: not provided | 128,252,033(+) | C/G | SYNONYMOUS_VARIANT | |
778362 | Benign: not provided | 128,252,093(+) | A/G | SYNONYMOUS_VARIANT | |
783831 | Benign: not provided | 128,254,568(+) | C/T | SYNONYMOUS_VARIANT | |
908787 | Uncertain Significance: Leptin deficiency or dysfunction | 128,256,081(+) | G/C | THREE_PRIME_UTR_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
leptin deficiency or dysfunction |
|
|
eating disorder |
|
|
glucose intolerance |
|
|
apnea, obstructive sleep |
|
|
bulimia nervosa |
|