LEPR

Summary

LEPR (leptin receptor, HGNC:6554) is a protein-coding gene on chromosome 1p31.3, encoding Leptin receptor (P48357). Receptor for hormone LEP/leptin.

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).

Source: NCBI Gene 3953 — RefSeq curated summary.

At a glance

• Gene–disease (curated): obesity due to leptin receptor gene deficiency (Strong, GenCC)
• GWAS associations: 77
• Clinical variants (ClinVar): 543 total — 18 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 32
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_002303

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6554
Approved symbol	LEPR
Name	leptin receptor
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	OBR, CD295, LEP-R, OB-R
Ensembl gene	ENSG00000116678
Ensembl biotype	protein_coding
OMIM	601007
Entrez	3953

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000344610, ENST00000349533, ENST00000371058, ENST00000371059, ENST00000371060, ENST00000462765, ENST00000471762, ENST00000616738

RefSeq mRNA: 6 — MANE Select: NM_002303 NM_001003679, NM_001003680, NM_001198687, NM_001198688, NM_001198689, NM_002303

CCDS: CCDS30740, CCDS30741, CCDS55604, CCDS631

Canonical transcript exons

ENST00000349533 — 20 exons

Exon	Start	End
ENSE00000000357	65420668	65420740
ENSE00001295071	65610214	65610296
ENSE00001298588	65617964	65618146
ENSE00001302126	65619928	65620023
ENSE00001303665	65616008	65616224
ENSE00001306788	65622906	65622981
ENSE00001310674	65636191	65641559
ENSE00003459486	65565546	65565605
ENSE00003504765	65621353	65621458
ENSE00003528068	65608753	65608901
ENSE00003547600	65572326	65572449
ENSE00003559375	65425303	65425378
ENSE00003575758	65601392	65601682
ENSE00003576938	65570473	65570802
ENSE00003585777	65598660	65598804
ENSE00003652322	65596448	65596593
ENSE00003664750	65601843	65601960
ENSE00003671220	65592657	65592865
ENSE00003683686	65609947	65610106
ENSE00003690482	65605038	65605237

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 98.83.

FANTOM5 (CAGE): breadth broad, TPM avg 10.9238 / max 1122.3550, expressed in 725 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3289	37.2493	1818
3302	7.2785	595
3297	1.8867	358
3293	0.5272	205
3301	0.4727	198
3288	0.2603	79
3295	0.2458	114
3299	0.0800	36
3298	0.0471	20
3294	0.0462	16

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	98.83	gold quality
choroid plexus epithelium	UBERON:0003911	98.53	gold quality
trigeminal ganglion	UBERON:0001675	98.41	gold quality
pericardium	UBERON:0002407	97.86	gold quality
skin of hip	UBERON:0001554	97.10	gold quality
oral cavity	UBERON:0000167	96.76	gold quality
pharyngeal mucosa	UBERON:0000355	96.52	gold quality
lower lobe of lung	UBERON:0008949	96.25	gold quality
upper leg skin	UBERON:0004262	95.75	gold quality
urethra	UBERON:0000057	95.49	gold quality
calcaneal tendon	UBERON:0003701	95.48	gold quality
cardia of stomach	UBERON:0001162	94.89	gold quality
dorsal root ganglion	UBERON:0000044	94.79	gold quality
mammary duct	UBERON:0001765	94.78	gold quality
vena cava	UBERON:0004087	94.53	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.20	gold quality
liver	UBERON:0002107	93.69	gold quality
synovial joint	UBERON:0002217	93.20	gold quality
cauda epididymis	UBERON:0004360	92.73	gold quality
visceral pleura	UBERON:0002401	92.50	gold quality
mammalian vulva	UBERON:0000997	92.49	gold quality
epithelium of mammary gland	UBERON:0003244	92.39	gold quality
body of tongue	UBERON:0011876	92.09	gold quality
thoracic mammary gland	UBERON:0005200	92.03	gold quality
mammary gland	UBERON:0001911	91.97	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.82	gold quality
pleura	UBERON:0000977	91.17	gold quality
right lobe of liver	UBERON:0001114	90.42	gold quality
parietal pleura	UBERON:0002400	90.27	gold quality
seminal vesicle	UBERON:0000998	90.18	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	1370.94
E-MTAB-5061	yes	572.20
E-GEOD-81608	yes	492.26
E-GEOD-81547	yes	408.38
E-ENAD-27	yes	402.20
E-GEOD-83139	yes	358.98
E-MTAB-10287	yes	65.16
E-CURD-112	yes	9.17
E-MTAB-10137	yes	4.00
E-GEOD-124858	no	184.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, KAT5, MT3, PPARG

miRNA regulators (miRDB)

22 targeting LEPR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-5591-3P	96.23	67.03	489
HSA-MIR-4522	95.76	66.23	742

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• A human liver cell line expresses the leptin receptor long form Ob-Rb in sufficient quantity to respond to leptin signalling in terms of STAT activation. (PMID:11448122)
• Cultured human articular chondrocytes express functional leptin receptor Ob-R, a receptor present on chondrocytes in native human cartilage. (PMID:11549273)
• Sleep apnea syndrome is associated with plasma soluble leptin receptor and insulin resistance independently of body mass index. (PMID:11896492)
• leptin receptors are expressed in breast cancer; data suggests they may be implicated in mammary cell proliferation and in breast cancer pathogenesis (PMID:11911959)
• the levels of mRNA for the long and total forms of leptin receptors were suppressed in association with the severity of endometriosis (PMID:11994543)
• results suggest that DNA sequence variations in the leptin receptor gene could affect substrate oxidation (PMID:12006639)
• presence of the long leptin receptor isoform in the absorptive cells of the small intestine, suggesting that leptin could have a physiological role in the regulation of nutrient absorption (PMID:12010881)
• confirmation of expression in primary osteoblasts (PMID:12054170)
• relationship of soluble leptin receptor with the degree of adiposity suggests that high SLR levels may enhance leptin action in lean subjects more than in obese subjects (PMID:12075576)
• regulation of circulating levels by gender, adiposity, sex steroids and leptin (PMID:12086939)
• Leptin receptor (Ob-R) expression is induced in peripheral blood mononuclear cells by in vitro activation and in vivo in HIV-infected patients, consistent with the suggested role of leptin in modulating the immune response. (PMID:12100031)
• during weight loss leptin levels decreased, whereas soluble leptin receptor levels and the receptor bound fraction of leptin increased (PMID:12105280)
• modifications in ciruclating levels across the eating disorder spectrum (PMID:12140788)
• Serum leptin and leptin binding activity in children and adolescents with hypothalamic dysfunction. (PMID:12199340)
• cloning, expression and purification of a recombinant leptin-binding domain (PMID:12226096)
• regulated shedding of the ectodomain of membrane-spanning leptin receptors may represent a novel mechanism of modulating leptin’s biological activity (PMID:12270921)
• transforming growth factor beta effects an increase in formation (PMID:12359239)
• high levels of soluble leptin receptor in emaciation may reflect an up-regulation to suppress leptin action during energy deficiency and with free leptin index is a tool to investigate the leptin axis during growth and sexual maturation (PMID:12364439)
• term pregnancy human umbilical cord and fetal membranes co-express leptin and its receptor genes (PMID:12396559)
• Significantly increased in anorexia nervosa patients. Increase unaffected by partial refeeding. Possible etiological role of increased soluble leptin receptor levels in anorexia nervosa by affecting leptin central and/or peripherial effects. (PMID:12489569)
• Human natural killer cell lines express leptin receptors. (PMID:12504075)
• the tumor clones in childhood acute lymphoblastic leukemia do not express the leptin receptor (PMID:12512839)
• higher leptin levels for those with a leptin receptor Lys109Arg or Gln223Arg mutation may imply that these subjects have a modified functional leptin receptor (PMID:12634434)
• Skillful mechanism where a change in the serum SLEPR level regulates, in part, the biological activity of leptin in the circulation. (PMID:12660261)
• in living cells approximately 60% of the leptin receptor exists as constitutive dimers at physiological expression levels in the absence of leptin (PMID:12734179)
• Serum adiponectin and soluble leptin receptor levels might be influenced by common regulatory factors and challenge the notion that cortisol may have a direct inhibitory effect on adiponectin in humans. (PMID:12788897)
• low serum leptin, high serum TGF-beta1 and sOb-R levels, and elevated urine leptin concentrations were observed at the onset of minimal change nephrotic syndrome (PMID:12898374)
• Possibility that soluble leptin receptor is a minor component of leptin binding capacity in the plasma of pregnant women. (PMID:14599116)
• role of the soluble leptin receptor (sOB-R) in maintaining serum leptin levels in nephrotic patients (PMID:14602796)
• Ob-R gene may serve as a novel modifier gene for hypercholesterolemia in Japanese men. (PMID:14625131)
• Hints for a peripheral role of leptin in the male genital tract, possibly, by an interaction between leptin and spermatozoa via sperm leptin receptors. (PMID:14636218)
• Soluble leptin receptor levels are not altered by the cyclic hormone status in the menstrual cycle. (PMID:14967380)
• LEPR single nucleotide polymorphisms contribute to variation in obesity phenotypes. (PMID:14970363)
• The leptin receptor is aberrantly expressed in bladder cancer tissue and is possibly involved in the carcinogenesis of bladder cancer. (PMID:14972512)
• Lower expression levels of leptin receptor short form (Ob-Ra) were observed in most endometrial cancer tissues, especially in the poorly differentiated ones. (PMID:14984939)
• Expression of leptin receptor in arcuate nucleus resulted in normalization of estrous cycle length, increased ovarian follicular development, and decreased serum progesterone levels. (PMID:14998906)
• plasma SLR levels are independently regulated by many different physiological and pathophysiological conditions and SLR may modulate the actions of leptin (PMID:15016839)
• low levels of expression of leptin receptors at the cell surface results from partial retention in the biosynthetic pathway, coupled to constitutive removal from the plasma membrane via ligand-independent, constitutive endocytosis (PMID:15123629)
• Secretory endometrium is target for leptin, and oocytes and preimplantation embryos possess OB-R mRNA. Leptin may be necessary for embryonic development. Leptin mRNA expressed at blastocysts stage. Possible function in blastocyst-endometrial dialogue. (PMID:15126576)
• Leptin receptor polymorphism (Gln223 Arg) has association with peak bone mass in young women. (PMID:15130412)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lepr	ENSDARG00000070961
mus_musculus	Lepr	ENSMUSG00000057722
rattus_norvegicus	Lepr	ENSRNOG00000023664

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL5RA (ENSG00000091181), IL12RB1 (ENSG00000096996), IL27RA (ENSG00000104998), EBI3 (ENSG00000105246), GHR (ENSG00000112964), PRLR (ENSG00000113494), LIFR (ENSG00000113594), CSF3R (ENSG00000119535), CNTFR (ENSG00000122756), IL13RA2 (ENSG00000123496), IL13RA1 (ENSG00000131724), IL6ST (ENSG00000134352), IL11RA (ENSG00000137070), OSMR (ENSG00000145623), IL2RG (ENSG00000147168), IL6R (ENSG00000160712), IL23R (ENSG00000162594), IL31RA (ENSG00000164509), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Protein

Protein identifiers

Leptin receptor — P48357 (reviewed: P48357)

Alternative names: HuB219, OB receptor

All UniProt accessions (1): P48357

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for hormone LEP/leptin. 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. 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. 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. May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. Does not induce phosphorylation of and activate STAT3. Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.

Subunit / interactions. Present as a mixture of monomers and dimers. The phosphorylated receptor binds a number of SH2 domain-containing proteins such as JAK2, STAT3, PTPN11, and SOCS3. Interaction with SOCS3 inhibits JAK/STAT signaling and MAPK cascade.

Subcellular location. Cell membrane. Basolateral cell membrane Secreted.

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. Isoform B and isoform A are expressed by NK cells (at protein level).

Post-translational modifications. 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.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. 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.

Similarity. Belongs to the type I cytokine receptor family. Type 2 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
P48357-1	B, 13.2, OBRb	yes
P48357-2	A, 6.4, HuB219.3
P48357-3	C, 12.1, OBRa
P48357-4	D, HuB219.2
P48357-5	E

RefSeq proteins (6): NP_001003679, NP_001003680, NP_001185616, NP_001185617, NP_001185618, NP_002294* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003529	Hematopoietin_rcpt_Gp130_CS	Conserved_site
IPR003531	Hempt_rcpt_S_F1_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR010457	IgC2-like_lig-bd	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR041182	LEP-R_IGD	Domain

Pfam: PF00041, PF06328, PF18589

UniProt features (88 total): glycosylation site 18, strand 15, sequence variant 11, disulfide bond 10, splice variant 7, domain 5, modified residue 4, region of interest 3, mutagenesis site 3, short sequence motif 2, topological domain 2, sequence conflict 2, helix 2, signal peptide 1, chain 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
3V6O	X-RAY DIFFRACTION	1.95
6E2P	X-RAY DIFFRACTION	2.83
8X85	ELECTRON MICROSCOPY	3.58
7Z3Q	X-RAY DIFFRACTION	3.62
8X81	ELECTRON MICROSCOPY	3.77
8X80	ELECTRON MICROSCOPY	3.88
8AVE	ELECTRON MICROSCOPY	5.62
8AVF	ELECTRON MICROSCOPY	6.45
8AVO	ELECTRON MICROSCOPY	6.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48357-F1	66.49	0.22

Antibody-complex structures (SAbDab): 1 — 3V6O

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 882, 986, 1079, 1141

Disulfide bonds (10): 37–90, 89–99, 131–142, 186–196, 188–193, 352–412, 413–418, 436–447, 473–528, 488–498

Glycosylation sites (18): 23, 41, 56, 73, 81, 98, 187, 206, 276, 347, 397, 516, 624, 659, 688, 697, 728, 750

Mutagenesis-validated functional residues (3):

Position	Phenotype
986	greatly reduced ptpn11 binding; no ptpn11 phosphorylation; no effect on stat3 phosphorylation.
1078–1079	no effect on ptpn11 nor stat3 phosphorylation.
1141	no effect on ptpn11 phosphorylation; no stat3 phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2586552	Signaling by Leptin

MSigDB gene sets: 389 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, WANG_CLIM2_TARGETS_UP, GOBP_BEHAVIOR, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_PEPTIDE, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, MODULE_64, GOZGIT_ESR1_TARGETS_DN, GOBP_GROWTH, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1

GO Biological Process (27): angiogenesis (GO:0001525), glycogen metabolic process (GO:0005977), gluconeogenesis (GO:0006094), energy reserve metabolic process (GO:0006112), phagocytosis (GO:0006909), cell surface receptor signaling pathway (GO:0007166), multicellular organism development (GO:0007275), cholesterol metabolic process (GO:0008203), positive regulation of cell population proliferation (GO:0008284), negative regulation of autophagy (GO:0010507), glial cell proliferation (GO:0014009), cytokine-mediated signaling pathway (GO:0019221), sexual reproduction (GO:0019953), T cell differentiation (GO:0030217), leptin-mediated signaling pathway (GO:0033210), glucose homeostasis (GO:0042593), response to leptin (GO:0044321), negative regulation of gluconeogenesis (GO:0045721), regulation of bone remodeling (GO:0046850), regulation of transport (GO:0051049), regulation of feeding behavior (GO:0060259), energy homeostasis (GO:0097009), cell surface receptor signaling pathway via STAT (GO:0097696), bone growth (GO:0098868), positive regulation of cold-induced thermogenesis (GO:0120162), transport across blood-brain barrier (GO:0150104), system development (GO:0048731)

GO Molecular Function (8): transmembrane signaling receptor activity (GO:0004888), cytokine receptor activity (GO:0004896), peptide hormone binding (GO:0017046), cytokine binding (GO:0019955), leptin receptor activity (GO:0038021), identical protein binding (GO:0042802), protein binding (GO:0005515), signaling receptor activity (GO:0038023)

GO Cellular Component (6): extracellular region (GO:0005576), external side of plasma membrane (GO:0009897), basolateral plasma membrane (GO:0016323), signaling receptor complex (GO:0043235), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	2
cytokine-mediated signaling pathway	2
protein binding	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
energy reserve metabolic process	1
glucan metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
energy derivation by oxidation of organic compounds	1
endocytosis	1
signal transduction	1
multicellular organismal process	1
anatomical structure development	1
sterol metabolic process	1
secondary alcohol metabolic process	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
gliogenesis	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
reproductive process	1
lymphocyte differentiation	1
T cell activation	1
cellular response to leptin stimulus	1
carbohydrate homeostasis	1
response to hormone	1
gluconeogenesis	1
regulation of gluconeogenesis	1
negative regulation of biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of small molecule metabolic process	1
regulation of tissue remodeling	1
bone remodeling	1
transport	1
regulation of localization	1

Protein interactions and networks

STRING

2156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LEPR	LEP	P41159	999
LEPR	POMC	P01189	917
LEPR	JAK2	O60674	904
LEPR	SOCS3	O14543	897
LEPR	INS	P01308	887
LEPR	MC4R	P32245	882
LEPR	AGRP	O00253	881
LEPR	BBS1	Q8NFJ9	872
LEPR	ADIPOQ	Q15848	869
LEPR	NPY	P01303	863
LEPR	STAT3	P40763	845
LEPR	LEPROT	O15243	844
LEPR	CARTPT	Q16568	840
LEPR	SNX4	O95219	791
LEPR	SNX2	P82862	770

IntAct

40 interactions, top by confidence:

A	B	Type	Score
LEPR	LEP	psi-mi:“MI:0407”(direct interaction)	0.700
LEP	LEPR	psi-mi:“MI:0914”(association)	0.700
LEPR	LEP	psi-mi:“MI:0915”(physical association)	0.700
LEP	LEPR	psi-mi:“MI:0915”(physical association)	0.700
GHSR	LEPR	psi-mi:“MI:0403”(colocalization)	0.610
GHSR	LEPR	psi-mi:“MI:2364”(proximity)	0.610
HCRTR1	LEPR	psi-mi:“MI:0403”(colocalization)	0.580
HCRTR1	LEPR	psi-mi:“MI:2364”(proximity)	0.580
LEPR	HCRTR1	psi-mi:“MI:0915”(physical association)	0.580
LEPR	LEPROT	psi-mi:“MI:0915”(physical association)	0.540
LEPR	LEPROT	psi-mi:“MI:0407”(direct interaction)	0.540
atp6v0d_human	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
PTPN11	LEPR	psi-mi:“MI:0914”(association)	0.530
LEPR	GRB2	psi-mi:“MI:0915”(physical association)	0.400
CSNK2B	LEPR	psi-mi:“MI:0915”(physical association)	0.370
LEPR	LEPR	psi-mi:“MI:2364”(proximity)	0.350
LEPR	JAK2	psi-mi:“MI:0914”(association)	0.350
BTNL8	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLURP1	MANBA	psi-mi:“MI:0914”(association)	0.350
DEFB107A	ZZEF1	psi-mi:“MI:0914”(association)	0.350
TAFA2	ERN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): LEPR (Affinity Capture-MS), LEPR (Reconstituted Complex), LEPR (Affinity Capture-MS), LEPR (Affinity Capture-MS), LEPR (Affinity Capture-MS), LEPR (Affinity Capture-MS), LEPR (Affinity Capture-MS), NDN (Two-hybrid), LEPR (Proximity Label-MS), LEPR (Protein-RNA), PTPN11 (Affinity Capture-Western), PTPN11 (Reconstituted Complex), LEPR (Synthetic Lethality), USP8 (Proximity Label-MS), LEPR (Proximity Label-MS)

ESM2 similar proteins: A0A2K5V015, A1YIY0, A8MUZ8, A8MWA4, B8JI71, O08569, P01133, P0DJ43, P14370, P14585, P17630, P19070, P48357, P82279, P97435, Q07444, Q0D2K5, Q28066, Q28660, Q29RU2, Q4KUS1, Q5G872, Q5R6R1, Q5RCW9, Q5T1H1, Q5UKY4, Q5Z5Q3, Q60736, Q63515, Q63722, Q6DFV8, Q6GMZ9, Q6V0K7, Q6ZN79, Q7TSY4, Q811Q4, Q8N2E2, Q8VHS2, Q90Y54, Q95MI4

Diamond homologs: O02671, P16471, P48356, P48357, Q62959, Q9MYL0, Q14213

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
LEPR	“up-regulates activity”	JAK2	binding
LEPR	“up-regulates activity”	STAT3	phosphorylation
JAK2	“up-regulates activity”	LEPR	phosphorylation
LEPR	“up-regulates activity”	STAT3	binding
LEPR	“up-regulates activity”	PTPN11	binding
LEPR	“down-regulates activity”	AMPK
LEP	up-regulates	LEPR	binding
LEPR	“up-regulates quantity”	POMC
LEPR	“down-regulates quantity”	NPY
LEPR	“down-regulates quantity”	AGRP
LEPR	“up-regulates activity”	SH2B1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of tumor necrosis factor production	5	27.4×	3e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

543 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	16
Uncertain significance	248
Likely benign	157
Benign	53

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2498024	NM_002303.6(LEPR):c.1874G>A (p.Trp625Ter)	Pathogenic
2814341	NM_002303.6(LEPR):c.253dup (p.Thr85fs)	Pathogenic
3030911	NM_002303.6(LEPR):c.1986_1990del (p.Leu663fs)	Pathogenic
3247939	NC_000001.10:g.(?66101854)(66102698_?)del	Pathogenic
3348212	NM_002303.6(LEPR):c.494+1G>T	Pathogenic
3351586	NM_002303.6(LEPR):c.1776del (p.Lys592fs)	Pathogenic
3351967	NM_002303.6(LEPR):c.1103G>A (p.Trp368Ter)	Pathogenic
3653406	NM_002303.6(LEPR):c.395G>A (p.Trp132Ter)	Pathogenic
421140	NM_002303.6(LEPR):c.93G>A (p.Trp31Ter)	Pathogenic
453309	NM_002303.6(LEPR):c.3268_3269dup (p.Ser1090fs)	Pathogenic
4726995	NM_002303.6(LEPR):c.359_360del (p.Phe120fs)	Pathogenic
4732471	NM_002303.6(LEPR):c.2396-2A>C	Pathogenic
4811500	NM_002303.6(LEPR):c.1846del (p.Arg615_Leu616insTer)	Pathogenic
596614	NM_002303.6(LEPR):c.2296A>T (p.Lys766Ter)	Pathogenic
596629	NM_002303.6(LEPR):c.479del (p.His160fs)	Pathogenic
619954	NM_002303.6(LEPR):c.464A>C (p.Tyr155Ser)	Pathogenic
666597	Single allele	Pathogenic
8522	NM_002303.6(LEPR):c.2597+1G>A	Pathogenic
1525833	NM_002303.6(LEPR):c.995-2A>G	Likely pathogenic
3242154	NM_002303.6(LEPR):c.1752+1G>A	Likely pathogenic
3340175	NM_002303.6(LEPR):c.2051A>C (p.His684Pro)	Likely pathogenic
3345031	NM_002303.6(LEPR):c.1501C>T (p.Gln501Ter)	Likely pathogenic
3345338	NM_002303.6(LEPR):c.1603+1G>T	Likely pathogenic
3347906	NM_002303.6(LEPR):c.1204C>T (p.Arg402Ter)	Likely pathogenic
3348213	NM_002303.6(LEPR):c.233del (p.His78fs)	Likely pathogenic
3351054	NM_002303.6(LEPR):c.1990T>A (p.Trp664Arg)	Likely pathogenic
3353366	NM_002303.6(LEPR):c.286_289delinsT (p.Asp96_Arg97delinsTer)	Likely pathogenic
3354244	NM_002303.6(LEPR):c.802C>T (p.Gln268Ter)	Likely pathogenic
3355139	NM_002303.6(LEPR):c.1265A>T (p.Tyr422Phe)	Likely pathogenic
3357044	NM_002303.6(LEPR):c.3G>A (p.Met1Ile)	Likely pathogenic

SpliceAI

5043 predictions. Top by Δscore:

Variant	Effect	Δscore
1:65425301:A:AG	acceptor_gain	1.0000
1:65425302:G:GG	acceptor_gain	1.0000
1:65425377:GG:G	donor_gain	1.0000
1:65425378:GG:G	donor_gain	1.0000
1:65425379:G:GG	donor_gain	1.0000
1:65429835:T:A	acceptor_gain	1.0000
1:65429835:T:TA	acceptor_gain	1.0000
1:65429836:G:A	acceptor_gain	1.0000
1:65429846:T:A	acceptor_gain	1.0000
1:65429847:G:A	acceptor_gain	1.0000
1:65494009:G:GT	donor_gain	1.0000
1:65596445:A:AG	acceptor_gain	1.0000
1:65596445:AAGT:A	acceptor_gain	1.0000
1:65596446:A:AG	acceptor_gain	1.0000
1:65596447:G:GA	acceptor_gain	1.0000
1:65596447:GT:G	acceptor_gain	1.0000
1:65596447:GTGAA:G	acceptor_gain	1.0000
1:65596589:GAGAA:G	donor_gain	1.0000
1:65596594:G:GG	donor_gain	1.0000
1:65597434:GA:G	donor_gain	1.0000
1:65598803:AGG:A	donor_loss	1.0000
1:65598805:GTAG:G	donor_loss	1.0000
1:65617962:A:AG	acceptor_gain	1.0000
1:65617963:G:GG	acceptor_gain	1.0000
1:65633260:G:T	donor_gain	1.0000
1:65420736:TAAAG:T	donor_loss	0.9900
1:65420738:AAGGT:A	donor_loss	0.9900
1:65420739:AGG:A	donor_loss	0.9900
1:65420740:GGTAC:G	donor_loss	0.9900
1:65420741:G:GA	donor_loss	0.9900

AlphaMissense

7731 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:65601896:T:C	C447R	0.996
1:65601863:T:C	C436R	0.995
1:65601896:T:A	C447S	0.995
1:65601897:G:C	C447S	0.995
1:65608821:T:A	W558R	0.995
1:65608821:T:C	W558R	0.995
1:65610061:A:C	S623R	0.995
1:65610063:T:A	S623R	0.995
1:65610063:T:G	S623R	0.995
1:65622957:G:C	W883C	0.995
1:65622957:G:T	W883C	0.995
1:65601499:T:A	W368R	0.994
1:65601499:T:C	W368R	0.994
1:65601864:G:A	C436Y	0.994
1:65622955:T:A	W883R	0.994
1:65622955:T:C	W883R	0.994
1:65601863:T:A	C436S	0.993
1:65601864:G:C	C436S	0.993
1:65601897:G:A	C447Y	0.993
1:65601898:C:G	C447W	0.993
1:65601902:T:A	W449R	0.993
1:65601902:T:C	W449R	0.993
1:65601904:G:C	W449C	0.993
1:65601904:G:T	W449C	0.993
1:65605126:T:C	C498R	0.992
1:65601865:T:G	C436W	0.991
1:65608823:G:C	W558C	0.991
1:65608823:G:T	W558C	0.991
1:65610070:A:C	S626R	0.991
1:65610072:C:A	S626R	0.991

dbSNP variants (sampled 300 via entrez): RS1000001524 (1:65459908 A>G), RS1000008257 (1:65483861 G>T), RS1000033733 (1:65454977 C>G,T), RS1000049408 (1:65498616 T>C), RS1000049870 (1:65550124 C>G,T), RS1000070706 (1:65449783 C>G,T), RS1000080591 (1:65583018 T>C), RS1000098917 (1:65537462 CT>C,CTT), RS1000106906 (1:65609277 C>T), RS1000141524 (1:65449181 C>T), RS1000144644 (1:65544783 T>C), RS1000178187 (1:65438423 G>A,T), RS1000183519 (1:65477297 C>T), RS1000206088 (1:65577290 T>C), RS1000207814 (1:65435681 C>T)

Disease associations

OMIM: gene MIM:601007 | disease phenotypes: MIM:614963, MIM:614962, MIM:601665

GenCC curated gene-disease

Disease	Classification	Inheritance
obesity due to leptin receptor gene deficiency	Strong	Autosomal recessive

Mondo (7): peripheral precocious puberty (MONDO:0015791), obesity due to leptin receptor gene deficiency (MONDO:0013992), monogenic diabetes (MONDO:0015967), obesity due to congenital leptin deficiency (MONDO:0013991), inherited obesity (MONDO:0019182), obesity disorder (MONDO:0011122), primary ovarian failure (MONDO:0005387)

Orphanet (8): Rare peripheral precocious puberty (Orphanet:178040), Obesity due to leptin receptor gene deficiency (Orphanet:179494), Rare genetic diabetes mellitus (Orphanet:183625), Obesity due to congenital leptin deficiency (Orphanet:66628), Genetic obesity (Orphanet:77828), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000712	Emotional lability
HP:0000718	Aggressive behavior
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000815	Hypergonadotropic hypogonadism
HP:0000819	Diabetes mellitus
HP:0000823	Delayed puberty
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000842	Hyperinsulinemia
HP:0001249	Intellectual disability
HP:0001513	Obesity
HP:0002155	Hypertriglyceridemia
HP:0002591	Polyphagia
HP:0002788	Recurrent upper respiratory tract infections
HP:0002958	Immune dysregulation
HP:0003292	Decreased serum leptin
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0004926	Orthostatic hypotension due to autonomic dysfunction
HP:0005419	Decreased T cell activation
HP:0005616	Accelerated skeletal maturation
HP:0008187	Absence of secondary sex characteristics
HP:0008214	Decreased serum estradiol
HP:0008245	Pituitary hypothyroidism
HP:0008724	Hypoplasia of the ovary
HP:0008734	Decreased testicular size
HP:0012286	Abnormal hypothalamus morphology
HP:0032218	Decreased CD4+ T cell proportion

GWAS associations

77 associations (top):

Study	Trait	p-value
GCST000178_2	C-reactive protein	7.000000e-21
GCST000292_4	Metabolic traits	4.000000e-07
GCST000430_4	C-reactive protein	3.000000e-14
GCST000605_1	Soluble leptin receptor levels	6.000000e-13
GCST000965_8	C-reactive protein levels	4.000000e-62
GCST001650_4	C-reactive protein	2.000000e-09
GCST001957_5	Obesity (early onset extreme)	2.000000e-09
GCST002086_4	C-reactive protein	9.000000e-09
GCST002147_14	Fibrinogen	5.000000e-14
GCST002541_27	Menarche (age at onset)	4.000000e-08
GCST002610_1	Fasting plasma glucose (childhood)	5.000000e-08
GCST002937_15	Molybdenum levels	8.000000e-06
GCST003194_12	Fibrinogen levels	4.000000e-15
GCST003681_6	C-reactive protein levels or triglyceride levels (pleiotropy)	8.000000e-36
GCST003994_11	Age at voice drop	1.000000e-10
GCST004121_9	Fibrinogen levels	5.000000e-12
GCST004122_31	Fibrinogen levels	5.000000e-11
GCST004602_10	Mean corpuscular volume	4.000000e-11
GCST004610_27	White blood cell count	2.000000e-16
GCST004613_12	Sum neutrophil eosinophil counts	9.000000e-20
GCST004614_111	Granulocyte count	1.000000e-19
GCST004614_112	Granulocyte count	4.000000e-37
GCST004620_111	Sum basophil neutrophil counts	8.000000e-20
GCST004626_58	Myeloid white cell count	8.000000e-19
GCST004626_59	Myeloid white cell count	8.000000e-36
GCST004629_7	Neutrophil count	5.000000e-20
GCST004630_7	Mean corpuscular hemoglobin	1.000000e-15
GCST004632_88	Lymphocyte percentage of white cells	8.000000e-10
GCST006585_480	Blood protein levels	0.000000e+00
GCST007614_24	C-reactive protein levels	2.000000e-162

EFO canonical traits (25, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004635	leptin receptor measurement
EFO:0004703	age at menarche
EFO:0004530	triglyceride measurement
EFO:0007888	age at voice drop
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0004527	mean corpuscular hemoglobin
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004340	body mass index
EFO:0005937	longitudinal BMI measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004509	hemoglobin measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5913 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1137101	Efficacy	3	simvastatin	Coronary Disease
rs1137101	Efficacy	3	simvastatin	Hyperlipidemias
rs1137101	Toxicity	3	valproic acid	Epilepsy
rs1137101	Toxicity	3	antipsychotics
rs1805094	Efficacy	3	atorvastatin	Acute coronary syndrome

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1137101	LEPR, LEPROT	3	2.50	4	simvastatin;valproic acid;antipsychotics
rs1805094	LEPR, LEPROT	3	1.25	1	atorvastatin
rs1045895	LEPR, LEPROT		0.00	0
rs6657868	LEPR		0.00	0
rs9436746	LEPR		0.00	0
rs1805096	LEPR		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — IL-6 receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
leptin	Agonist	10.19	pKd

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	4
methylmercuric chloride	increases expression, decreases expression	2
bisphenol A	decreases methylation, increases expression	2
trichostatin A	decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Arsenic	affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
Simvastatin	affects response to substance	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
pirinixic acid	increases activity, increases expression, affects binding	1
lead acetate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
1-aminomethylphosphonic acid	decreases expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1291112	Binding	Displacement of [125I]-Leptin from leptin receptor at 1 to 3 uM	Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols. — Bioorg Med Chem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 1 hybrid cell line, 1 transformed cell line, 1 factor-dependent cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4457	SN-56/OBR	Hybrid cell line
CVCL_D7TH	Ubigene A-549 LEPR KO	Cancer cell line	Male
CVCL_D8P6	Ubigene HCT 116 LEPR KO	Cancer cell line	Male
CVCL_D9II	Ubigene HEK293 LEPR KO	Transformed cell line	Female
CVCL_E0GF	Ubigene HeLa LEPR KO	Cancer cell line	Female
CVCL_K248	Baf3/WSX E63x7 sort	Factor-dependent cell line
CVCL_SV45	HAP1 LEPR (-)	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	PHASE4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)
NCT00699413	PHASE4	TERMINATED	Supplements for Controlling Resistance to Insulin
NCT00729963	PHASE4	COMPLETED	Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients