LEPR

Protein identityUniProt · HPA

UniProt accession

P48357

Gene

LEPR

Ensembl

ENSG00000116678

Chromosome

1

Canonical length

1165 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted membrane proteins

Subcellular location

Vesicles,Plasma membrane,Primary cilium,Basal body,Cytosol

Secretome location

Intracellular and membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1165 residues, UniProt reviewed canonical sequence.

>P48357|LEPR
     1  MICQKFCVVL LHWEFIYVIT AFNLSYPITP WRFKLSCMPP NSTYDYFLLP AGLSKNTSNS
    61  NGHYETAVEP KFNSSGTHFS NLSKTTFHCC FRSEQDRNCS LCADNIEGKT FVSTVNSLVF
   121  QQIDANWNIQ CWLKGDLKLF ICYVESLFKN LFRNYNYKVH LLYVLPEVLE DSPLVPQKGS
   181  FQMVHCNCSV HECCECLVPV PTAKLNDTLL MCLKITSGGV IFQSPLMSVQ PINMVKPDPP
   241  LGLHMEITDD GNLKISWSSP PLVPFPLQYQ VKYSENSTTV IREADKIVSA TSLLVDSILP
   301  GSSYEVQVRG KRLDGPGIWS DWSTPRVFTT QDVIYFPPKI LTSVGSNVSF HCIYKKENKI
   361  VPSKEIVWWM NLAEKIPQSQ YDVVSDHVSK VTFFNLNETK PRGKFTYDAV YCCNEHECHH
   421  RYAELYVIDV NINISCETDG YLTKMTCRWS TSTIQSLAES TLQLRYHRSS LYCSDIPSIH
   481  PISEPKDCYL QSDGFYECIF QPIFLLSGYT MWIRINHSLG SLDSPPTCVL PDSVVKPLPP
   541  SSVKAEITIN IGLLKISWEK PVFPENNLQF QIRYGLSGKE VQWKMYEVYD AKSKSVSLPV
   601  PDLCAVYAVQ VRCKRLDGLG YWSNWSNPAY TVVMDIKVPM RGPEFWRIIN GDTMKKEKNV
   661  TLLWKPLMKN DSLCSVQRYV INHHTSCNGT WSEDVGNHTK FTFLWTEQAH TVTVLAINSI
   721  GASVANFNLT FSWPMSKVNI VQSLSAYPLN SSCVIVSWIL SPSDYKLMYF IIEWKNLNED
   781  GEIKWLRISS SVKKYYIHDH FIPIEKYQFS LYPIFMEGVG KPKIINSFTQ DDIEKHQSDA
   841  GLYVIVPVII SSSILLLGTL LISHQRMKKL FWEDVPNPKN CSWAQGLNFQ KPETFEHLFI
   901  KHTASVTCGP LLLEPETISE DISVDTSWKN KDEMMPTTVV SLLSTTDLEK GSVCISDQFN
   961  SVNFSEAEGT EVTYEDESQR QPFVKYATLI SNSKPSETGE EQGLINSSVT KCFSSKNSPL
  1021  KDSFSNSSWE IEAQAFFILS DQHPNIISPH LTFSEGLDEL LKLEGNFPEE NNDKKSIYYL
  1081  GVTSIKKRES GVLLTDKSRV SCPFPAPCLF TDIRVLQDSC SHFVENNINL GTSSKKTFAS
  1141  YMPQFQTCST QTHKIMENKM CDLTV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LEPR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

122 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LEPR.

Disease | AllUniProt

Conditions LEPR is implicated in, by any mechanism.

• Leptin receptor deficiency (LEPRD) MIM:614963

Disease | GeneticClinVar

34 pathogenic / likely-pathogenic of 526 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• LEPR-related disorder
• Obesity due to leptin receptor gene deficiency
• Obesity
• Early onset severe obesity
• Obesity due to congenital leptin deficiency

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.28

gnomAD pLI

0.99

gnomAD missense Z

1.42

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• bone growth
• cell surface receptor signaling pathway
• cell surface receptor signaling pathway via STAT
• cholesterol metabolic process
• cytokine-mediated signaling pathway
• energy homeostasis
• energy reserve metabolic process
• glial cell proliferation
• gluconeogenesis
• glucose homeostasis
• glycogen metabolic process
• leptin-mediated signaling pathway
• multicellular organism development
• negative regulation of autophagy
• negative regulation of gluconeogenesis
• phagocytosis
• positive regulation of cell population proliferation
• positive regulation of cold-induced thermogenesis
• regulation of bone remodeling
• regulation of feeding behavior
• regulation of transport
• response to leptin
• sexual reproduction
• T cell differentiation
• transport across blood-brain barrier

Molecular functions

• cytokine binding
• cytokine receptor activity
• identical protein binding
• peptide hormone binding
• transmembrane signaling receptor activity
• leptin receptor activity

Cellular components

• basolateral plasma membrane
• external side of plasma membrane
• extracellular region
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Long hematopoietin receptor, Gp130 family 2, conserved site
• Short hematopoietin receptor, family 1, conserved site
• Fibronectin type III
• Immunoglobulin-like domain
• Immunoglobulin C2-set-like, ligand-binding
• Immunoglobulin-like fold
• Fibronectin type III superfamily
• Fibronectin type III domain
• Ig-like C2-type domain
• Leptin receptor, immunoglobulin-like domain
• Obesity receptor immunoglobulin like domain

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Membrane
• Obesity
• Phosphoprotein
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of LEPR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• JAK2
• LEPROT