LEPR (leptin receptor)

Gene

• Entrez ID: 3953
• Gene name: Leptin receptor
• Gene symbol: LEPR
• Synonyms: CD295, LEP-R, LEPRD, OB-R, OBR
• Chromosome: 1
• Chromosome location: 1p31.3
• Summary: The protein encoded by this gene belongs to the gp130 family of cytokine receptors that are known to stimulate gene transcription via activation of cytosolic STAT proteins. This protein is a receptor for leptin (an adipocyte-specific hormone that regulates body weight), and is involved in the regulation of fat metabolism, as well as in a novel hematopoietic pathway that is required for normal lymphopoiesis. Mutations in this gene have been associated with obesity and pituitary dysfunction. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. It is noteworthy that this gene and LEPROT gene (GeneID:54741) share the same promoter and the first 2 exons, however, encode distinct proteins (PMID:9207021).[provided by RefSeq, Nov 2010]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs144159890	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs193922650	C>G,T	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, synonymous variant
rs765551290	A>T	Pathogenic	Stop gained, coding sequence variant
rs945135468	G>A	Pathogenic-likely-pathogenic	Coding sequence variant, stop gained
rs1446132233	C>A,G	Likely-pathogenic	Coding sequence variant, missense variant
rs1474810899	G>A,T	Pathogenic	Splice donor variant
rs1553174844	->AG	Pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant
rs1557670950	A>C	Pathogenic	Coding sequence variant, missense variant
rs1557670990	A>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017009	hsa-miR-335-5p	Microarray	18185580
MIRT037290	hsa-miR-877-5p	CLASH	23622248
MIRT734277	hsa-miR-200c-3p	Luciferase reporter assay, Microarray, Western blot	25840984

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001525	Process	Angiogenesis	IMP	21771332
GO:0001934	Process	Positive regulation of protein phosphorylation	IDA	27037668
GO:0004888	Function	Transmembrane signaling receptor activity	TAS	9537324
GO:0004896	Function	Cytokine receptor activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	11279102, 17474147, 18042720, 19910644, 28717967
GO:0005576	Component	Extracellular region	IEA
GO:0005977	Process	Glycogen metabolic process	IEA
GO:0006112	Process	Energy reserve metabolic process	TAS	9537324
GO:0006909	Process	Phagocytosis	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	TAS	9537324
GO:0007275	Process	Multicellular organism development	TAS	9537324
GO:0008203	Process	Cholesterol metabolic process	IEA
GO:0009897	Component	External side of plasma membrane	IBA	21873635
GO:0010507	Process	Negative regulation of autophagy	IDA	25060689
GO:0014009	Process	Glial cell proliferation	IEA
GO:0016021	Component	Integral component of membrane	IEA
GO:0016323	Component	Basolateral plasma membrane	IEA
GO:0017046	Function	Peptide hormone binding	IBA	21873635
GO:0019221	Process	Cytokine-mediated signaling pathway	IBA	21873635
GO:0019953	Process	Sexual reproduction	ISS
GO:0019955	Function	Cytokine binding	IBA	21873635
GO:0030217	Process	T cell differentiation	ISS
GO:0033210	Process	Leptin-mediated signaling pathway	IBA	21873635
GO:0033210	Process	Leptin-mediated signaling pathway	IDA	27037668
GO:0033210	Process	Leptin-mediated signaling pathway	ISS
GO:0038021	Function	Leptin receptor activity	IDA	20977476, 27037668
GO:0038021	Function	Leptin receptor activity	ISS
GO:0042593	Process	Glucose homeostasis	ISS
GO:0042802	Function	Identical protein binding	IPI	16116438
GO:0043235	Component	Receptor complex	IBA	21873635
GO:0043235	Component	Receptor complex	IDA	23382219
GO:0044321	Process	Response to leptin	ISS
GO:0045721	Process	Negative regulation of gluconeogenesis	IEA
GO:0046850	Process	Regulation of bone remodeling	ISS
GO:0051049	Process	Regulation of transport	IDA	20977476
GO:0051346	Process	Negative regulation of hydrolase activity	IEA
GO:0060259	Process	Regulation of feeding behavior	ISS
GO:0097009	Process	Energy homeostasis	ISS
GO:0098868	Process	Bone growth	ISS
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	11003997
GO:0150104	Process	Transport across blood-brain barrier	NAS	26590417, 30280653

Other IDs

• MIM: 601007
• HGNC: 6554
• e!Ensembl: ENSG00000116678

Protein

• UniProt ID: P48357
• Protein name: Leptin receptor (LEP-R) (HuB219) (OB receptor) (OB-R) (CD antigen CD295)
• Protein function: 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:25060689, PubMed:12504075, 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). ; [Isoform A]: May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. Does not induce phosphorylation of and activate STAT3. ; [Isoform E]: Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.
• PDB: 3V6O, 6E2P
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF18589	ObR_Ig	126 → 233	Obesity receptor immunoglobulin like domain	Domain
  PF06328	Lep_receptor_Ig	329 → 420	Ig-like C2-type domain	Domain
  PF18589	ObR_Ig	431 → 533	Obesity receptor immunoglobulin like domain	Domain

• Sequence:

  MICQKFCVVLLHWEFIYVITAFNLSYPITPWRFKLSCMPPNSTYDYFLLPAGLSKNTSNS
  NGHYETAVEPKFNSSGTHFSNLSKTTFHCCFRSEQDRNCSLCADNIEGKTFVSTVNSLVF
  QQIDANWNIQCWLKGDLKLFICYVESLFKNLFRNYNYKVHLLYVLPEVLEDSPLVPQKGS
  FQMVHCNCSVHECCECLVPVPTAKLNDTLLMCLKITSGGVIFQSPLMSVQPINMVKPDPP
  LGLHMEITDDGNLKISWSSPPLVPFPLQYQVKYSENSTTVIREADKIVSATSLLVDSILP
  GSSYEVQVRGKRLDGPGIWSDWSTPRVFTTQDVIYFPPKILTSVGSNVSFHCIYKKENKI
  VPSKEIVWWMNLAEKIPQSQYDVVSDHVSKVTFFNLNETKPRGKFTYDAVYCCNEHECHH
  RYAELYVIDVNINISCETDGYLTKMTCRWSTSTIQSLAESTLQLRYHRSSLYCSDIPSIH
  PISEPKDCYLQSDGFYECIFQPIFLLSGYTMWIRINHSLGSLDSPPTCVLPDSVVKPLPP
  SSVKAEITINIGLLKISWEKPVFPENNLQFQIRYGLSGKEVQWKMYEVYDAKSKSVSLPV
  PDLCAVYAVQVRCKRLDGLGYWSNWSNPAYTVVMDIKVPMRGPEFWRIINGDTMKKEKNV
  TLLWKPLMKNDSLCSVQRYVINHHTSCNGTWSEDVGNHTKFTFLWTEQAHTVTVLAINSI
  GASVANFNLTFSWPMSKVNIVQSLSAYPLNSSCVIVSWILSPSDYKLMYFIIEWKNLNED
  GEIKWLRISSSVKKYYIHDHFIPIEKYQFSLYPIFMEGVGKPKIINSFTQDDIEKHQSDA
  GLYVIVPVIISSSILLLGTLLISHQRMKKLFWEDVPNPKNCSWAQGLNFQKPETFEHLFI
  KHTASVTCGPLLLEPETISEDISVDTSWKNKDEMMPTTVVSLLSTTDLEKGSVCISDQFN
  SVNFSEAEGTEVTYEDESQRQPFVKYATLISNSKPSETGEEQGLINSSVTKCFSSKNSPL
  KDSFSNSSWEIEAQAFFILSDQHPNIISPHLTFSEGLDELLKLEGNFPEENNDKKSIYYL
  GVTSIKKRESGVLLTDKSRVSCPFPAPCLFTDIRVLQDSCSHFVENNINLGTSSKKTFAS
  YMPQFQTCSTQTHKIMENKMCDLTV

• Sequence length: 1165