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Aliases for LEPR Gene

Aliases for LEPR Gene

  • Leptin Receptor 2 3 5
  • OB Receptor 3 4
  • HuB219 3 4
  • LEP-R 3 4
  • OB-R 3 4
  • OBR 3 4
  • CD295 Antigen 4
  • CD295 3
  • LEPRD 3
  • DB 4

External Ids for LEPR Gene

Previous GeneCards Identifiers for LEPR Gene

  • GC01P065838
  • GC01P064841
  • GC01P065244
  • GC01P065257
  • GC01P065258
  • GC01P065599
  • GC01P065603
  • GC01P065659
  • GC01P065886
  • GC01P063995

Summaries for LEPR Gene

Entrez Gene Summary for LEPR 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]

GeneCards Summary for LEPR Gene

LEPR (Leptin Receptor) is a Protein Coding gene. Diseases associated with LEPR include obesity, morbid, due to leptin receptor deficiency and obesity. Among its related pathways are Adipocytokine signaling pathway and AMPK signaling pathway. GO annotations related to this gene include identical protein binding and cytokine receptor activity.

UniProtKB/Swiss-Prot for LEPR Gene

  • 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.

Tocris Summary for LEPR Gene

  • 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.

Gene Wiki entry for LEPR Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for LEPR Gene

Genomics for LEPR Gene

Regulatory Elements for LEPR Gene

Enhancers for LEPR Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around LEPR on UCSC Golden Path with GeneCards custom track

Promoters for LEPR Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around LEPR on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the LEPR gene promoter:

Genomic Location for LEPR Gene

Chromosome:
1
Start:
65,420,652 bp from pter
End:
65,641,559 bp from pter
Size:
220,908 bases
Orientation:
Plus strand

Genomic View for LEPR Gene

Genes around LEPR on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LEPR Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LEPR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LEPR Gene

Proteins for LEPR Gene

  • Protein details for LEPR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P48357-LEPR_HUMAN
    Recommended name:
    Leptin receptor
    Protein Accession:
    P48357
    Secondary Accessions:
    • Q13592
    • Q13593
    • Q13594
    • Q92919
    • Q92920
    • Q92921

    Protein attributes for LEPR Gene

    Size:
    1165 amino acids
    Molecular mass:
    132494 Da
    Quaternary structure:
    • Present as a mixture of monomers and dimers (Probable). The phosphorylated receptor binds a number of SH2 domain-containing proteins such as JAK2, STAT3, PTPN11, and SOCS3 (By similarity) (PubMed:9600917). Interaction with SOCS3 inhibits JAK/STAT signaling and MAPK cascade (By similarity).

    Three dimensional structures from OCA and Proteopedia for LEPR Gene

    Alternative splice isoforms for LEPR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LEPR Gene

Proteomics data for LEPR Gene at MOPED

Post-translational modifications for LEPR Gene

  • On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-986 is required for complete binding and activation of PTPN11, ERK/FOS activation,for interaction with SOCS3 and SOCS3 mediated inhibition of leptin signaling. Phosphorylation on Tyr-1141 is required for STAT3 binding/activation. Phosphorylation of Tyr-1079 has a more accessory role.
  • Glycosylation at Asn 23, Asn 41, Asn 56, Asn 73, Asn 81, Asn 98, Asn 187, Asn 206, Asn 276, Asn 347, Asn 397, Asn 516, Asn 624, Asn 659, Asn 688, Asn 697, Asn 728, and Asn 750
  • Modification sites at PhosphoSitePlus

Antibody Products

No data available for DME Specific Peptides for LEPR Gene

Domains & Families for LEPR Gene

Suggested Antigen Peptide Sequences for LEPR Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P48357

UniProtKB/Swiss-Prot:

LEPR_HUMAN :
  • The cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase and STATs.
  • Belongs to the type I cytokine receptor family. Type 2 subfamily.
Domain:
  • The cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase and STATs.
  • The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
  • The box 1 motif is required for JAK interaction and/or activation.
  • Contains 4 fibronectin type-III domains.
  • Contains 1 Ig-like (immunoglobulin-like) domain.
Family:
  • Belongs to the type I cytokine receptor family. Type 2 subfamily.
genes like me logo Genes that share domains with LEPR: view

Function for LEPR Gene

Molecular function for LEPR Gene

GENATLAS Biochemistry:
obese gene (leptin) receptor,16kDa,with two alternatively spliced forms,short ubiquitously expressed,long predominantly expressed in hypothalamus,homolog with mouse db,also expressed in human vasculature and in primary cultures of endothelial cells
UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot Function:
Isoform A: May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. Does not induce phosphorylation of and activate STAT3.
UniProtKB/Swiss-Prot Function:
Isoform E: Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.

Gene Ontology (GO) - Molecular Function for LEPR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0042802 identical protein binding IPI 20347812
genes like me logo Genes that share ontologies with LEPR: view
genes like me logo Genes that share phenotypes with LEPR: view

Human Phenotype Ontology for LEPR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for LEPR Gene

MGI Knock Outs for LEPR:

Animal Model Products

  • Taconic Biosciences Mouse Models for LEPR

miRNA for LEPR Gene

miRTarBase miRNAs that target LEPR

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for LEPR Gene

Localization for LEPR Gene

Subcellular locations from UniProtKB/Swiss-Prot for LEPR Gene

Cell membrane; Single-pass type I membrane protein. Basolateral cell membrane.
Isoform E: Secreted.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for LEPR Gene COMPARTMENTS Subcellular localization image for LEPR gene
Compartment Confidence
plasma membrane 5
extracellular 4
nucleus 2
peroxisome 2
cytosol 1
endoplasmic reticulum 1
mitochondrion 1
vacuole 1

Gene Ontology (GO) - Cellular Components for LEPR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with LEPR: view

Pathways & Interactions for LEPR Gene

genes like me logo Genes that share pathways with LEPR: view

SIGNOR curated interactions for LEPR Gene

Is activated by:

Gene Ontology (GO) - Biological Process for LEPR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007166 cell surface receptor signaling pathway TAS 9537324
GO:0007275 multicellular organism development TAS 9537324
GO:0008203 cholesterol metabolic process IEA --
GO:0019953 sexual reproduction ISS --
GO:0030217 T cell differentiation IEA,ISS --
genes like me logo Genes that share ontologies with LEPR: view

Drugs & Compounds for LEPR Gene

(33) Drugs for LEPR Gene - From: DrugBank, PharmGKB, DGIdb, IUPHAR, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
atorvastatin Approved Pharma Competitive, Inhibitor 0
Simvastatin Approved Pharma Competitive, Inhibitor HMG-CoA reductase inhibitor 499
Valproic Acid Approved, Investigational Pharma HDAC1 inhibitor, Histone deacetylase (HDAC)inhibitors 312
Leptin Investigational Pharma Agonist, inhibitor, Target 0
LEP (116-130) (mouse) Pharma An antiobesity hormone, Synthetic leptin peptide fragment 0

(21) Additional Compounds for LEPR Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(1) Tocris Compounds for LEPR Gene

Compound Action Cas Number
LEP (116-130) (mouse) Synthetic leptin peptide fragment 258276-95-8
genes like me logo Genes that share compounds with LEPR: view

Transcripts for LEPR Gene

Unigene Clusters for LEPR Gene

Leptin receptor:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for LEPR Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^
SP1: - - - -
SP2:
SP3: -
SP4:

ExUns: 23
SP1:
SP2:
SP3:
SP4:

Relevant External Links for LEPR Gene

GeneLoc Exon Structure for
LEPR
ECgene alternative splicing isoforms for
LEPR

Expression for LEPR Gene

mRNA expression in normal human tissues for LEPR Gene

mRNA differential expression in normal tissues according to GTEx for LEPR Gene

This gene is overexpressed in Liver (x6.3).

Protein differential expression in normal tissues from HIPED for LEPR Gene

This gene is overexpressed in Cerebral cortex (51.8) and Gallbladder (10.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for LEPR Gene



SOURCE GeneReport for Unigene cluster for LEPR Gene Hs.723178

mRNA Expression by UniProt/SwissProt for LEPR Gene

P48357-LEPR_HUMAN
Tissue specificity: Isoform A is expressed in fetal liver and in hematopoietic tissues and choroid plexus. In adults highest expression in heart, liver, small intestine, prostate and ovary. Low level in lung and kidney. Isoform B is highly expressed in hypothalamus, but also in skeletal muscle. Detected in fundic and antral epithelial cells of the gastric mucosa (PubMed:19159218). Isoform B and isoform A are expressed by NK cells (at protein level) (PubMed:12504075).
genes like me logo Genes that share expression patterns with LEPR: view

Primer Products

No data available for Protein tissue co-expression partners for LEPR Gene

Orthologs for LEPR Gene

This gene was present in the common ancestor of chordates.

Orthologs for LEPR Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia LEPR 35
  • 88.65 (n)
  • 83.32 (a)
OB-R 36
  • 83 (a)
OneToOne
dog
(Canis familiaris)
Mammalia LEPR 35
  • 88.46 (n)
  • 83.76 (a)
LEPR 36
  • 84 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Lepr 35
  • 81.83 (n)
  • 75.71 (a)
Lepr 16
Lepr 36
  • 76 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia LEPR 35
  • 99.31 (n)
  • 98.88 (a)
LEPR 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Lepr 35
  • 81.77 (n)
  • 75.97 (a)
oppossum
(Monodelphis domestica)
Mammalia LEPR 36
  • 65 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LEPR 36
  • 51 (a)
OneToOne
chicken
(Gallus gallus)
Aves LEPR 35
  • 60.78 (n)
  • 48.93 (a)
LEPR 36
  • 48 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LEPR 36
  • 50 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia lepr 35
  • 56.11 (n)
  • 42.37 (a)
zebrafish
(Danio rerio)
Actinopterygii lepr 35
  • 45.02 (n)
  • 31.54 (a)
lepr 36
  • 27 (a)
OneToOne
Species with no ortholog for LEPR:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for LEPR Gene

ENSEMBL:
Gene Tree for LEPR (if available)
TreeFam:
Gene Tree for LEPR (if available)

Paralogs for LEPR Gene

No data available for Paralogs for LEPR Gene

Variants for LEPR Gene

Sequence variations from dbSNP and Humsavar for LEPR Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs1137100 - 65,570,758(+) AGGAA(A/G)GACAT reference, missense
VAR_002704 -
rs1137101 - 65,592,830(+) TTTCC(A/G)GTCAC reference, missense
VAR_002706 -
VAR_002707 -

Structural Variations from Database of Genomic Variants (DGV) for LEPR Gene

Variant ID Type Subtype PubMed ID
nsv830070 CNV Gain 17160897
nsv528808 CNV Gain 19592680
nsv830081 CNV Gain 17160897
esv2521430 CNV Deletion 19546169
esv2015767 CNV Deletion 18987734
esv4385 CNV Deletion 18987735
esv2749218 CNV Deletion 23290073
esv2630441 CNV Deletion 19546169
nsv160318 CNV Loss 16902084
nsv1176 CNV Loss 18451855
nsv870752 CNV Gain 21882294
nsv823109 CNV Gain 20364138
nsv870656 CNV Gain 21882294
nsv461705 CNV Gain 19166990
dgv232n71 CNV Gain 21882294
esv2615796 CNV Deletion 19546169
nsv508260 CNV Loss 20534489
nsv1188 CNV Loss 18451855
nsv436459 CNV Deletion 17901297
esv2661943 CNV Deletion 23128226
nsv498671 CNV Loss 21111241
esv2749229 CNV Deletion 23290073
esv2580170 CNV Deletion 19546169
esv1978491 CNV Deletion 18987734
esv28812 CNV Loss 19812545
esv2665242 CNV Deletion 23128226
esv2464074 CNV Loss 19546169
esv2572647 CNV Insertion 19546169
esv269871 CNV Insertion 20981092
esv274382 CNV Insertion 20981092
esv1474810 CNV Insertion 17803354
esv2079710 CNV Deletion 18987734
esv2749240 CNV Deletion 23290073
esv5181 CNV Deletion 18987735
esv2749252 CNV Deletion 23290073
esv9112 CNV Loss 19470904
nsv819065 CNV Loss 19587683

Variation tolerance for LEPR Gene

Residual Variation Intolerance Score: 11.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.99; 89.98% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for LEPR Gene

HapMap Linkage Disequilibrium report
LEPR
Human Gene Mutation Database (HGMD)
LEPR

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LEPR Gene

Disorders for LEPR Gene

MalaCards: The human disease database

(22) MalaCards diseases for LEPR Gene - From: OMIM, ClinVar, GeneTests, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
obesity, morbid, due to leptin receptor deficiency
  • leptin receptor deficiency
obesity
  • obesity, association with
clostridium difficile colitis
  • pseudomembranous colitis
morbid obesity
  • severe obesity
fatty liver disease
  • alcoholic fatty liver
- elite association - COSMIC cancer census association via MalaCards
Search LEPR in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

LEPR_HUMAN
  • Leptin receptor deficiency (LEPRD) [MIM:614963]: A rare disease characterized by normal levels of serum leptin, hyperphagia and severe obesity from an early age. Additional features include alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. {ECO:0000269 PubMed:25751111, ECO:0000269 PubMed:9537324}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for LEPR Gene

early-onset morbid obesity,absence of pubertal development (hypogonadotropic hypogonadism),and reduced secretion of growth hormone and thyrotropin

Relevant External Links for LEPR

Genetic Association Database (GAD)
LEPR
Human Genome Epidemiology (HuGE) Navigator
LEPR
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
LEPR
genes like me logo Genes that share disorders with LEPR: view

Publications for LEPR Gene

  1. Leptin receptor gene variation and obesity: lack of association in a white British male population. (PMID: 9175732) Gotoda T. … Aitman T.J. (Hum. Mol. Genet. 1997) 3 4 48 67
  2. Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance. (PMID: 19717488) Fuentes T. … Guerra B. (Exp. Physiol. 2010) 3 23
  3. Leptin-R and its association with PI3K/AKT signaling pathway in papillary thyroid carcinoma. (PMID: 20008098) Uddin S. … Al-Kuraya K.S. (Endocr. Relat. Cancer 2010) 3 23
  4. Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults. (PMID: 20032477) Phillips C.M. … Roche H.M. (J. Nutr. 2010) 3 23
  5. Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma. (PMID: 20045163) Cheng S.P. … Liu C.L. (Surgery 2010) 3 23

Products for LEPR Gene

Sources for LEPR Gene

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