MCID: LPT006
MIFTS: 38

Leptin Receptor Deficiency

Categories: Genetic diseases, Reproductive diseases, Endocrine diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Leptin Receptor Deficiency

MalaCards integrated aliases for Leptin Receptor Deficiency:

Name: Leptin Receptor Deficiency 57 25 75 37 29 6 73
Obesity, Morbid, Due to Leptin Receptor Deficiency 57 25 13
Obesity Due to Leptin Receptor Gene Deficiency 25 59
Obesity, Morbid, Nonsyndromic 2 57 25
Morbid Obesity Due to Leptin Receptor Deficiency 75
Congenital Deficiency of the Leptin Receptor 25
Leptin Receptor-Related Monogenic Obesity 25
Non-Syndromic Morbid Obesity 2 75
Deficiency, Leptin Receptor 40
Leptin Receptor 13
Leprd 75

Characteristics:

Orphanet epidemiological data:

59
obesity due to leptin receptor gene deficiency
Inheritance: Autosomal recessive;

Classifications:



Summaries for Leptin Receptor Deficiency

Genetics Home Reference : 25 Leptin receptor deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. The extreme hunger leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret.

MalaCards based summary : Leptin Receptor Deficiency, also known as obesity, morbid, due to leptin receptor deficiency, is related to obesity due to congenital leptin deficiency and lung cancer. An important gene associated with Leptin Receptor Deficiency is LEPR (Leptin Receptor), and among its related pathways/superpathways are Neuroactive ligand-receptor interaction and Adipocytokine signaling pathway. The drugs alpha-MSH and Hormone Antagonists have been mentioned in the context of this disorder. Affiliated tissues include t cells, hypothalamus and pituitary, and related phenotypes are obesity and decreased serum leptin

UniProtKB/Swiss-Prot : 75 Leptin receptor deficiency: 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.

Wikipedia : 76 Leptin receptor also known as LEP-R or OB-R is a Type I cytokine receptor, a protein that in humans is... more...

Description from OMIM: 614963

Related Diseases for Leptin Receptor Deficiency

Diseases related to Leptin Receptor Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 obesity due to congenital leptin deficiency 11.1
2 lung cancer 10.6
3 breast cancer 10.1
4 diabetes mellitus, noninsulin-dependent 10.1
5 osteoporosis 9.7
6 diabetes mellitus 9.7
7 glucose intolerance 9.7
8 influenza 9.7
9 autonomic dysfunction 9.7
10 hypoxia 9.7
11 body mass index quantitative trait locus 11 9.0 LEPR LEPROT

Graphical network of the top 20 diseases related to Leptin Receptor Deficiency:



Diseases related to Leptin Receptor Deficiency

Symptoms & Phenotypes for Leptin Receptor Deficiency

Clinical features from OMIM:

614963

Human phenotypes related to Leptin Receptor Deficiency:

59 32 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 obesity 59 32 obligate (100%) Obligate (100%) HP:0001513
2 decreased serum leptin 59 32 obligate (100%) Obligate (100%) HP:0003292
3 gynecomastia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000771
4 primary amenorrhea 59 32 hallmark (90%) Very frequent (99-80%) HP:0000786
5 hypergonadotropic hypogonadism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000815
6 hyperinsulinemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000842
7 polyphagia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002591
8 decreased t cell activation 59 32 hallmark (90%) Very frequent (99-80%) HP:0005419
9 absence of secondary sex characteristics 59 32 hallmark (90%) Very frequent (99-80%) HP:0008187
10 decreased serum estradiol 59 32 hallmark (90%) Very frequent (99-80%) HP:0008214
11 decreased testosterone in males 59 32 hallmark (90%) Very frequent (99-80%) HP:0008230
12 hypoplasia of the ovary 59 32 hallmark (90%) Very frequent (99-80%) HP:0008724
13 decreased testicular size 59 32 hallmark (90%) Very frequent (99-80%) HP:0008734
14 emotional lability 59 32 frequent (33%) Frequent (79-30%) HP:0000712
15 insulin-resistant diabetes mellitus 59 32 frequent (33%) Frequent (79-30%) HP:0000831
16 hypertriglyceridemia 59 32 frequent (33%) Frequent (79-30%) HP:0002155
17 recurrent upper respiratory tract infections 59 32 frequent (33%) Frequent (79-30%) HP:0002788
18 orthostatic hypotension due to autonomic dysfunction 59 32 frequent (33%) Frequent (79-30%) HP:0004926
19 accelerated skeletal maturation 59 32 frequent (33%) Frequent (79-30%) HP:0005616
20 pituitary hypothyroidism 59 32 frequent (33%) Frequent (79-30%) HP:0008245
21 decreased number of cd4+ t cells 59 Very frequent (99-80%)
22 aggressive behavior 32 obligate (100%) HP:0000718
23 delayed puberty 32 HP:0000823
24 growth hormone deficiency 32 HP:0000824
25 immune dysregulation 32 HP:0002958
26 abnormal hypothalamus morphology 32 obligate (100%) HP:0012286
27 decreased proportion of cd4-positive t cells 32 hallmark (90%) HP:0005407

MGI Mouse Phenotypes related to Leptin Receptor Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.62 LEPR LEPROT

Drugs & Therapeutics for Leptin Receptor Deficiency

Drugs for Leptin Receptor Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 alpha-MSH Phase 3,Phase 2 581-05-5
2 Hormone Antagonists Phase 3,Phase 2
3 Hormones Phase 3,Phase 2
4 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 3,Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Setmelanotide for the Treatment of LEPR Deficiency Obesity Recruiting NCT03287960 Phase 3 setmelanotide;Placebo
2 Setmelanotide Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity Recruiting NCT03013543 Phase 2, Phase 3 Setmelanotide

Search NIH Clinical Center for Leptin Receptor Deficiency

Genetic Tests for Leptin Receptor Deficiency

Genetic tests related to Leptin Receptor Deficiency:

# Genetic test Affiliating Genes
1 Leptin Receptor Deficiency 29 LEPR

Anatomical Context for Leptin Receptor Deficiency

MalaCards organs/tissues related to Leptin Receptor Deficiency:

41
T Cells, Hypothalamus, Pituitary, Ovary, Nk Cells, Lung, Brain

Publications for Leptin Receptor Deficiency

Articles related to Leptin Receptor Deficiency:

(show all 21)
# Title Authors Year
1
MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. ( 29736023 )
2018
2
Potential role of gender specific effect of leptin receptor deficiency in an extended consanguineous family with severe early-onset obesity. ( 29545012 )
2018
3
Validity of leptin receptor-deficiency (db/db) type 2 diabetes mellitus mice as a model of secondary osteoporosis. ( 27283954 )
2016
4
Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice. ( 25791744 )
2015
5
The daidzein- and estradiol- induced anorectic action in CCK or leptin receptor deficiency rats. ( 25765851 )
2015
6
Leptin receptor deficiency confers resistance to behavioral effects of fluoxetine and desipramine via separable substrates. ( 25463972 )
2014
7
Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages. ( 25232724 )
2014
8
Increased central and peripheral inflammation and inflammatory hyperalgesia in Zucker rat model of leptin receptor deficiency and genetic obesity. ( 22523380 )
2012
9
Haematopoietic leptin receptor deficiency does not affect macrophage accumulation in adipose tissue or systemic insulin sensitivity. ( 22194312 )
2012
10
Neuropeptide Y and agouti-related peptide mediate complementary functions of hyperphagia and reduced energy expenditure in leptin receptor deficiency. ( 21285324 )
2011
11
Diabetic hypertensive leptin receptor-deficient db/db mice develop cardioregulatory autonomic dysfunction. ( 19029483 )
2009
12
Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesity. ( 18984941 )
2009
13
The effect of leptin receptor deficiency and fasting on cannabinoid receptor 1 mRNA expression in the rat hypothalamus, brainstem and nodose ganglion. ( 19596404 )
2009
14
Leptin receptor deficiency is associated with upregulation of cannabinoid 1 receptors in limbic brain regions. ( 18563836 )
2008
15
Swim training improves leptin receptor deficiency-induced obesity and lipid disorder by activating uncoupling proteins. ( 17603293 )
2007
16
Indirect effects of leptin receptor deficiency on lymphocyte populations and immune response in db/db mice. ( 16920925 )
2006
17
Leptin receptor-deficient obese Zucker rats reduce their food intake in response to hypobaric hypoxia. ( 16234269 )
2006
18
Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) female mice do not develop oncogene-induced mammary tumors. ( 14734797 )
2004
19
Transgenic complementation of leptin receptor deficiency. II. Increased leptin receptor transgene dose effects on obesity/diabetes and fertility/lactation in lepr-db/db mice. ( 14600075 )
2004
20
Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. ( 12413939 )
2002
21
Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene. ( 11272157 )
2001

Variations for Leptin Receptor Deficiency

ClinVar genetic disease variations for Leptin Receptor Deficiency:

6
(show top 50) (show all 63)
# Gene Variation Type Significance SNP ID Assembly Location
1 LEPR LEPR, IVS16, G-A, +1 single nucleotide variant Pathogenic
2 LEPR NM_002303.5(LEPR): c.-161C> T single nucleotide variant Uncertain significance rs372078226 GRCh38 Chromosome 1, 65420676: 65420676
3 LEPR NM_002303.5(LEPR): c.-161C> T single nucleotide variant Uncertain significance rs372078226 GRCh37 Chromosome 1, 65886359: 65886359
4 LEPR NM_002303.5(LEPR): c.-120C> T single nucleotide variant Uncertain significance rs189950527 GRCh38 Chromosome 1, 65420717: 65420717
5 LEPR NM_002303.5(LEPR): c.-120C> T single nucleotide variant Uncertain significance rs189950527 GRCh37 Chromosome 1, 65886400: 65886400
6 LEPR NM_002303.5(LEPR): c.-20-15A> T single nucleotide variant Uncertain significance rs116571599 GRCh38 Chromosome 1, 65565531: 65565531
7 LEPR NM_002303.5(LEPR): c.-20-15A> T single nucleotide variant Uncertain significance rs116571599 GRCh37 Chromosome 1, 66031214: 66031214
8 LEPR NM_002303.5(LEPR): c.921G> C (p.Gln307His) single nucleotide variant Uncertain significance rs531183918 GRCh38 Chromosome 1, 65598731: 65598731
9 LEPR NM_002303.5(LEPR): c.921G> C (p.Gln307His) single nucleotide variant Uncertain significance rs531183918 GRCh37 Chromosome 1, 66064414: 66064414
10 LEPR NM_002303.5(LEPR): c.1246C> T (p.His416Tyr) single nucleotide variant Uncertain significance rs144710810 GRCh38 Chromosome 1, 65601643: 65601643
11 LEPR NM_002303.5(LEPR): c.1246C> T (p.His416Tyr) single nucleotide variant Uncertain significance rs144710810 GRCh37 Chromosome 1, 66067326: 66067326
12 LEPR NM_002303.5(LEPR): c.2103C> T (p.Phe701=) single nucleotide variant Uncertain significance rs755504289 GRCh38 Chromosome 1, 65616115: 65616115
13 LEPR NM_002303.5(LEPR): c.2103C> T (p.Phe701=) single nucleotide variant Uncertain significance rs755504289 GRCh37 Chromosome 1, 66081798: 66081798
14 LEPR NM_002303.5(LEPR): c.3078T> C (p.Asn1026=) single nucleotide variant Uncertain significance rs34130975 GRCh38 Chromosome 1, 65636595: 65636595
15 LEPR NM_002303.5(LEPR): c.3078T> C (p.Asn1026=) single nucleotide variant Uncertain significance rs34130975 GRCh37 Chromosome 1, 66102278: 66102278
16 LEPR NM_002303.5(LEPR): c.3479T> C (p.Met1160Thr) single nucleotide variant Uncertain significance rs145685060 GRCh38 Chromosome 1, 65636996: 65636996
17 LEPR NM_002303.5(LEPR): c.3479T> C (p.Met1160Thr) single nucleotide variant Uncertain significance rs145685060 GRCh37 Chromosome 1, 66102679: 66102679
18 LEPR NM_002303.5(LEPR): c.*112T> C single nucleotide variant Uncertain significance rs886046506 GRCh37 Chromosome 1, 66102810: 66102810
19 LEPR NM_002303.5(LEPR): c.*112T> C single nucleotide variant Uncertain significance rs886046506 GRCh38 Chromosome 1, 65637127: 65637127
20 LEPR NM_002303.5(LEPR): c.371A> G (p.Asp124Gly) single nucleotide variant Uncertain significance rs35573508 GRCh38 Chromosome 1, 65572326: 65572326
21 LEPR NM_002303.5(LEPR): c.371A> G (p.Asp124Gly) single nucleotide variant Uncertain significance rs35573508 GRCh37 Chromosome 1, 66038009: 66038009
22 LEPR NM_002303.5(LEPR): c.536G> A (p.Gly179Asp) single nucleotide variant Uncertain significance rs151190195 GRCh38 Chromosome 1, 65592698: 65592698
23 LEPR NM_002303.5(LEPR): c.536G> A (p.Gly179Asp) single nucleotide variant Uncertain significance rs151190195 GRCh37 Chromosome 1, 66058381: 66058381
24 LEPR NM_002303.5(LEPR): c.1166G> A (p.Ser389Asn) single nucleotide variant Uncertain significance rs780534740 GRCh38 Chromosome 1, 65601563: 65601563
25 LEPR NM_002303.5(LEPR): c.1166G> A (p.Ser389Asn) single nucleotide variant Uncertain significance rs780534740 GRCh37 Chromosome 1, 66067246: 66067246
26 LEPR NM_002303.5(LEPR): c.2698A> G (p.Ile900Val) single nucleotide variant Uncertain significance rs142647085 GRCh38 Chromosome 1, 65636215: 65636215
27 LEPR NM_002303.5(LEPR): c.2698A> G (p.Ile900Val) single nucleotide variant Uncertain significance rs142647085 GRCh37 Chromosome 1, 66101898: 66101898
28 LEPR NM_002303.5(LEPR): c.3019A> T (p.Ser1007Cys) single nucleotide variant Uncertain significance rs145651189 GRCh38 Chromosome 1, 65636536: 65636536
29 LEPR NM_002303.5(LEPR): c.3019A> T (p.Ser1007Cys) single nucleotide variant Uncertain significance rs145651189 GRCh37 Chromosome 1, 66102219: 66102219
30 LEPR NM_002303.5(LEPR): c.3114A> G (p.Ile1038Met) single nucleotide variant Uncertain significance rs886046505 GRCh38 Chromosome 1, 65636631: 65636631
31 LEPR NM_002303.5(LEPR): c.3114A> G (p.Ile1038Met) single nucleotide variant Uncertain significance rs886046505 GRCh37 Chromosome 1, 66102314: 66102314
32 LEPR NM_002303.5(LEPR): c.*188A> C single nucleotide variant Uncertain significance rs886046507 GRCh37 Chromosome 1, 66102886: 66102886
33 LEPR NM_002303.5(LEPR): c.*188A> C single nucleotide variant Uncertain significance rs886046507 GRCh38 Chromosome 1, 65637203: 65637203
34 LEPR NM_002303.5(LEPR): c.*362_*363delCA deletion Benign rs796868878 GRCh37 Chromosome 1, 66103060: 66103061
35 LEPR NM_002303.5(LEPR): c.*362_*363delCA deletion Benign rs796868878 GRCh38 Chromosome 1, 65637377: 65637378
36 LEPR NM_002303.5(LEPR): c.*403T> C single nucleotide variant Uncertain significance rs375886561 GRCh37 Chromosome 1, 66103101: 66103101
37 LEPR NM_002303.5(LEPR): c.*403T> C single nucleotide variant Uncertain significance rs375886561 GRCh38 Chromosome 1, 65637418: 65637418
38 LEPR NM_002303.5(LEPR): c.-122T> C single nucleotide variant Benign rs3790435 GRCh38 Chromosome 1, 65420715: 65420715
39 LEPR NM_002303.5(LEPR): c.-122T> C single nucleotide variant Benign rs3790435 GRCh37 Chromosome 1, 65886398: 65886398
40 LEPR NM_002303.5(LEPR): c.-92C> T single nucleotide variant Uncertain significance rs13306523 GRCh38 Chromosome 1, 65425307: 65425307
41 LEPR NM_002303.5(LEPR): c.-92C> T single nucleotide variant Uncertain significance rs13306523 GRCh37 Chromosome 1, 65890990: 65890990
42 LEPR NM_002303.5(LEPR): c.666C> G (p.Phe222Leu) single nucleotide variant Uncertain significance rs886046503 GRCh38 Chromosome 1, 65592828: 65592828
43 LEPR NM_002303.5(LEPR): c.666C> G (p.Phe222Leu) single nucleotide variant Uncertain significance rs886046503 GRCh37 Chromosome 1, 66058511: 66058511
44 LEPR NM_002303.5(LEPR): c.1029T> C (p.Ser343=) single nucleotide variant Likely benign rs1805134 GRCh38 Chromosome 1, 65601426: 65601426
45 LEPR NM_002303.5(LEPR): c.1029T> C (p.Ser343=) single nucleotide variant Likely benign rs1805134 GRCh37 Chromosome 1, 66067109: 66067109
46 LEPR NM_002303.5(LEPR): c.3057G> A (p.Pro1019=) single nucleotide variant Benign rs1805096 GRCh38 Chromosome 1, 65636574: 65636574
47 LEPR NM_002303.5(LEPR): c.3057G> A (p.Pro1019=) single nucleotide variant Benign rs1805096 GRCh37 Chromosome 1, 66102257: 66102257
48 LEPR NM_002303.5(LEPR): c.*201C> T single nucleotide variant Uncertain significance rs577287309 GRCh37 Chromosome 1, 66102899: 66102899
49 LEPR NM_002303.5(LEPR): c.*201C> T single nucleotide variant Uncertain significance rs577287309 GRCh38 Chromosome 1, 65637216: 65637216
50 LEPR NM_002303.5(LEPR): c.716C> T (p.Pro239Leu) single nucleotide variant Uncertain significance rs886046504 GRCh38 Chromosome 1, 65596460: 65596460

Expression for Leptin Receptor Deficiency

Search GEO for disease gene expression data for Leptin Receptor Deficiency.

Pathways for Leptin Receptor Deficiency

Pathways related to Leptin Receptor Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Neuroactive ligand-receptor interaction hsa04080
2 Adipocytokine signaling pathway hsa04920
3 Jak-STAT signaling pathway hsa04630
4 AMPK signaling pathway hsa04152
5 Cytokine-cytokine receptor interaction hsa04060

GO Terms for Leptin Receptor Deficiency

Sources for Leptin Receptor Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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