Leptin Deficiency or Dysfunction disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

LEPD MCID: LPT014 MIFTS: 78	Leptin Deficiency or Dysfunction (LEPD) Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Reproductive diseases	Data Licensing For inquiries, contact: [email protected]
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Aliases & Classifications for Leptin Deficiency or Dysfunction

MalaCards integrated aliases for Leptin Deficiency or Dysfunction:

Name: Leptin Deficiency or Dysfunction ⁵⁷ ¹¹ ¹⁹ ⁷³ ⁷¹

Obesity Due to Congenital Leptin Deficiency ¹¹ ¹⁹ ⁴² ⁵⁸ ⁷³ ²⁸ ⁵

Morbid Obesity ¹¹ ⁷³ ²⁸ ⁵ ¹⁴ ¹⁶

Lepd ⁵⁷ ¹¹ ¹⁹ ⁴² ⁷³

Congenital Leptin Deficiency ¹¹ ⁴² ¹⁴ ⁷¹

Obesity, Morbid ⁵⁷ ⁴³ ⁷¹

Obesity, Morbid, Due to Leptin Deficiency ⁵⁷ ⁴²

Obesity, Severe, Due to Leptin Deficiency ⁴² ³⁸

Obesity, Morbid, Nonsyndromic 1 ¹⁹ ⁴²

Leptin Deficiency ⁴² ⁷³

Severe Obesity ¹¹ ¹⁴

Morbid Obesity Due to Leptin Deficiency ⁷³

Leptin Dysfunction ⁵

Obesity Morbid ⁵³

Leptin ¹⁶

Characteristics:

Inheritance:

Leptin Deficiency or Dysfunction: Autosomal recessive ⁵⁷

Obesity Due to Congenital Leptin Deficiency: Autosomal recessive ⁵⁸

Prevelance:

Obesity Due to Congenital Leptin Deficiency: <1/1000000 (Worldwide) ⁵⁸

Age Of Onset:

Obesity Due to Congenital Leptin Deficiency: Childhood ⁵⁸

OMIM®:

⁵⁷ (Updated 08-Dec-2022)

Miscellaneous:
some patients have a secreted but biologically inactive mutant leptin
hyperphagia and weight gain as well as immunologic abnormalities and hypogonadism can be reversed by exogenously administered recombinant leptin
patients do not exhibit risk factors for cardiovascular disease such as hypertension, lipid dysregulation, or hyperglycemia
immune and endocrine function may improve in some adult patients

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Reproductive diseases Endocrine diseases Neuronal diseases

See all MalaCards categories (disease lists)

ICD10: ³²

Endocrine, nutritional and metabolic diseases

Obesity and other hyperalimentation

Obesity

Other obesity

Orphanet: ⁵⁸

Rare infertility disorders

Rare gynaecological and obstetric diseases

Rare endocrine diseases

External Ids:

Disease Ontology ¹¹ DOID:0111334 DOID:11981

OMIM® ⁵⁷ 614962

ICD9CM ³⁴ 278.01

MeSH ⁴³ D009767

NCIt ⁴⁹ C34858

SNOMED-CT ⁶⁸ 389986000

ICD10 via Orphanet ³² E66.8

Orphanet ⁵⁸ ORPHA66628

MedGen ⁴⁰ C3554224 CN069970

EFO ¹⁶ EFO_0001074 EFO_0003199

UMLS ⁷¹ C0028756 C3554224 C3838754

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Summaries for Leptin Deficiency or Dysfunction

MedlinePlus Genetics: ⁴² Congenital leptin 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. Without treatment, the extreme hunger continues and 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.People with congenital leptin deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Without treatment, affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile).

MalaCards based summary: Leptin Deficiency or Dysfunction, also known as obesity due to congenital leptin deficiency, is related to gastroesophageal reflux and non-alcoholic fatty liver disease, and has symptoms including obesity, metabolically benign An important gene associated with Leptin Deficiency or Dysfunction is LEP (Leptin), and among its related pathways/superpathways are GPCR downstream signalling and Signal Transduction. The drugs Nadroparin and Sodium citrate have been mentioned in the context of this disorder. Affiliated tissues include adipocyte, liver and ovary, and related phenotypes are obesity and decreased serum leptin

Disease Ontology: ¹¹ A syndrome characterized by severe early-onset obesity, hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine and metabolic dysfunction that has material basis in homozygous or compound heterozygous mutation in LEP on chromosome 7q32.1.

GARD: ¹⁹ Leptin deficiency is characterized by severe early-onset obesity, hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic dysfunction (Ozata et al., 1999).

OMIM®: ⁵⁷ Leptin deficiency is characterized by severe early-onset obesity, hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic dysfunction (Ozata et al., 1999). (614962) (Updated 08-Dec-2022)

Orphanet: ⁵⁸ Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia.

UniProtKB/Swiss-Prot: ⁷³ A rare disease characterized by low levels of serum leptin, severe hyperphagia and intractable obesity from an early age.

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Related Diseases for Leptin Deficiency or Dysfunction

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

(show top 50) (show all 1441)

#	Related Disease	Score	Top Affiliating Genes
1	gastroesophageal reflux	31.9	PYY NPY GHRL GCG CCK ADIPOQ
2	non-alcoholic fatty liver disease	31.9	RETN PPARG LPL LEPR LEP INS
3	apnea, obstructive sleep	31.8	RETN PYY POMC LEP INS GHRL
4	sleep apnea	31.7	RETN PPARG NPY MC4R LEPR LEP
5	non-alcoholic steatohepatitis	31.7	PPARG LEP INS GCG ADIPOQ
6	fatty liver disease	31.7	RETN PPARG LPL LEPR LEP INS
7	liver disease	31.7	RETN PPARG LEPR LEP INS ADIPOQ
8	lipid metabolism disorder	31.6	RETN PPARG POMC LPL LEPR LEP
9	abdominal obesity-metabolic syndrome 1	31.6	RETN PPARG LPL LEPR LEP INS
10	nutritional deficiency disease	31.5	RETN PYY NPY LEPR LEP GHRL
11	cholelithiasis	31.5	LEP INS CCK
12	alcohol dependence	31.5	PPARG POMC NPY LEP INS GHRL
13	type 2 diabetes mellitus	31.5	UCP3 RETN PYY PPARG POMC PCSK1
14	eating disorder	31.4	RETN PYY POMC NPY MC4R LEPR
15	hernia, hiatus	31.4	LEP INS GHRL
16	bulimia nervosa	31.4	PYY NPY MC4R LEP INS GHRL
17	dumping syndrome	31.3	PYY INS GHRL GCG CCK
18	obesity-hypoventilation syndrome	31.3	RETN LEP ADIPOQ
19	osteoporosis	31.3	RETN PPARG LEPR LEP INS GHRL
20	volvulus of midgut	31.2	PYY GCG CCK
21	gestational diabetes	31.2	RETN PPARG LEPR LEP INS GHRL
22	peptic ulcer disease	31.2	INS GHRL CCK
23	liver cirrhosis	31.2	RETN NPY LEPR LEP INS GCG
24	prediabetes syndrome	31.1	UCP3 RETN PPARG NPY MC4R LPL
25	prader-willi syndrome	31.1	SIM1 RETN PYY POMC PCSK1 NPY
26	alcohol use disorder	31.1	POMC NPY INS
27	type 1 diabetes mellitus	31.1	LPL LEPR LEP INS GHRL GCG
28	hypoglycemia	31.1	POMC NPY LEP INS GHRL GCG
29	diabetes mellitus	31.1	UCP3 RETN PYY PPARG POMC PCSK1
30	atherosclerosis susceptibility	31.1	RETN PPARG LPL LEP INS ADIPOQ
31	hyperuricemia	31.0	PPARG LEP INS ADRB3
32	anxiety	31.0	POMC NPY LEP INS GHRL CCK
33	lipodystrophy, congenital generalized, type 2	31.0	PPARG LEP INS ADIPOQ
34	pain agnosia	31.0	POMC INS CCK
35	glucose intolerance	31.0	RETN PPARG POMC LPL LEPR LEP
36	irritable bowel syndrome	31.0	PYY POMC GHRL GCG CCK
37	lipodystrophy, familial partial, type 2	31.0	PPARG LEP INS ADIPOQ
38	proteasome-associated autoinflammatory syndrome 1	31.0	RETN PPARG INS ADIPOQ
39	hyperglycemia	31.0	RETN PYY PPARG LPL LEP INS
40	persistent fetal circulation syndrome	31.0	POMC LEP INS
41	peripheral nervous system disease	31.0	PPARG POMC NPY LEP INS GCG
42	kidney disease	31.0	RETN PPARG MC4R LEP INS GHRL
43	hyperinsulinemic hypoglycemia	30.9	POMC INS GCG
44	chronic kidney disease	30.9	LPL LEP INS GHRL ADIPOQ
45	heart disease	30.9	RETN PPARG NPY LPL INS GCG
46	polycystic ovary syndrome	30.9	RETN PPARG POMC LEP INS GHRL
47	carcinoid syndrome	30.9	PYY NPY
48	coronary heart disease 1	30.9	LPL INS ADIPOQ
49	cardiovascular system disease	30.8	RETN PPARG NPY LPL LEPR LEP
50	migraine with or without aura 1	30.8	POMC NPY LEP INS GCG CCK

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

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Symptoms & Phenotypes for Leptin Deficiency or Dysfunction

Human phenotypes related to Leptin Deficiency or Dysfunction:

⁵⁸ ³⁰ (show all 27)

#	Description	HPO Frequency	Orphanet Frequency	HPO Source Accession
1	obesity ⁵⁸ ³⁰	Obligate (100%)	Obligate (100%)	HP:0001513
2	decreased serum leptin ⁵⁸ ³⁰	Obligate (100%)	Obligate (100%)	HP:0003292
3	primary amenorrhea ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0000786
4	hyperinsulinemia ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0000842
5	gynecomastia ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0000771
6	decreased testicular size ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0008734
7	hypergonadotropic hypogonadism ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0000815
8	decreased serum estradiol ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0008214
9	polyphagia ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0002591
10	hypoplasia of the ovary ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0008724
11	absence of secondary sex characteristics ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0008187
12	decreased t cell activation ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0005419
13	decreased serum testosterone concentration ³⁰	Hallmark (90%)		HP:0040171
14	decreased proportion of cd4-positive helper t cells ³⁰	Hallmark (90%)		HP:0005407
15	hypertriglyceridemia ⁵⁸ ³⁰	Frequent (33%)	Frequent (79-30%)	HP:0002155
16	recurrent upper respiratory tract infections ⁵⁸ ³⁰	Frequent (33%)	Frequent (79-30%)	HP:0002788
17	accelerated skeletal maturation ⁵⁸ ³⁰	Frequent (33%)	Frequent (79-30%)	HP:0005616
18	orthostatic hypotension due to autonomic dysfunction ⁵⁸ ³⁰	Frequent (33%)	Frequent (79-30%)	HP:0004926
19	pituitary hypothyroidism ⁵⁸ ³⁰	Frequent (33%)	Frequent (79-30%)	HP:0008245
20	insulin-resistant diabetes mellitus ⁵⁸ ³⁰	Frequent (33%)	Frequent (79-30%)	HP:0000831
21	micropenis ³⁰			HP:0000054
22	recurrent pneumonia ³⁰			HP:0006532
23	hypogonadism ³⁰			HP:0000135
24	decreased testosterone in males ⁵⁸		Very frequent (99-80%)
25	decreased proportion of cd4-positive t cells ⁵⁸		Very frequent (99-80%)
26	abnormal eating behavior ³⁰			HP:0100738
27	recurrent ear infections ³⁰			HP:0410018

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 08-Dec-2022)

Genitourinary Internal Genitalia Female:
primary amenorrhea
small ovaries

Genitourinary:
hypogonadism

Growth Weight:
normal birth weight
early-onset severe obesity

Genitourinary Internal Genitalia Male:
small testes

Abdomen Gastrointestinal:
hyperphagia

Respiratory Lung:
recurrent pulmonary infections

Skin Nails Hair Hair:
no beard
sparse pubic and axillary hair

Immunology:
frequent infections in childhood
reduced number of ct4+ t cells (in some patients)
increase in cd8+ t cells (in some patients)
increase in b cells (in some patients)
marked reduction in cd4+/cd8+ ratio (in some patients)
more

Chest Breasts:
gynecomastia

Head And Neck Ears:
recurrent ear infections

Genitourinary External Genitalia Male:
small penis

Endocrine Features:
low testosterone levels
low estradiol levels
low serum leptin levels (in most patients)
high serum leptin levels (rare)
hypothalamic hypogonadism
more

Neurologic Behavioral Psychiatric Manifestations:
hyperphagia

Respiratory Nasopharynx:
frequent upper respiratory tract infections

Neurologic Peripheral Nervous System:
sympathetic system dysfunction

Clinical features from OMIM®:

614962 (Updated 08-Dec-2022)

UMLS symptoms related to Leptin Deficiency or Dysfunction:

obesity, metabolically benign

GenomeRNAi Phenotypes related to Leptin Deficiency or Dysfunction according to GeneCards Suite gene sharing:

²⁵

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	no effect	GR00402-S-1	10.17	ADIPOQ ADRB3 AGRP CCK GCG GHRL
2	no effect	GR00402-S-2	10.17	ADIPOQ ADRB3 AGRP CCK GCG GHRL

MGI Mouse Phenotypes related to Leptin Deficiency or Dysfunction:

⁴⁵ (show all 11)

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	adipose tissue	MP:0005375	10.28	ADIPOQ ADRB3 AGRP GHRL INS LEP
2	nervous system	MP:0003631	10.27	ADIPOQ AGRP CCK INS LEP LEPR
3	homeostasis/metabolism	MP:0005376	10.26	ADIPOQ ADRB3 AGRP CCK GCG GHRL
4	renal/urinary system	MP:0005367	10.17	ADIPOQ CCK GCG INS LEP LEPR
5	normal	MP:0002873	10.15	AGRP GHRL INS LEPR MC4R NPY
6	liver/biliary system	MP:0005370	10.11	ADIPOQ AGRP INS LEP LEPR LPL
7	growth/size/body region	MP:0005378	10.09	ADIPOQ ADRB3 AGRP GCG INS LEP
8	muscle	MP:0005369	10.06	ADIPOQ INS LEP LEPR LPL PCSK1
9	no phenotypic analysis	MP:0003012	10.02	AGRP CCK INS LEPR MC4R POMC
10	endocrine/exocrine gland	MP:0005379	9.77	ADIPOQ ADRB3 CCK GCG GHRL INS
11	behavior/neurological	MP:0005386	9.5	ADIPOQ ADRB3 AGRP GHRL INS LEP

Sources

Drugs & Therapeutics for Leptin Deficiency or Dysfunction

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

(show top 50) (show all 384)

Name

Status

Phase

Clinical Trials

Cas Number

PubChem Id

Nadroparin

Approved, Investigational

Phase 4

Sodium citrate

Approved, Investigational

Phase 4

68-04-2

23431961

Octreotide

Approved, Investigational

Phase 4

83150-76-9

383414 6400441

Clomifene

Approved, Investigational

Phase 4

911-45-5

2800

Mecobalamin

Approved, Investigational

Phase 4

13422-55-4

Hydroxocobalamin

Approved

Phase 4

13422-51-0

15589840 44475014

Risedronic acid

Approved, Investigational

Phase 4

105462-24-6

5245

Sevoflurane

Approved, Vet_approved

Phase 4

28523-86-6

5206

Remifentanil

Approved

Phase 4

132875-61-7

60815

Tocopherol

Approved, Investigational

Phase 4

1406-66-2

Ropivacaine

Approved

Phase 4

84057-95-4

71273 175805

Miconazole

Approved, Investigational, Vet_approved

Phase 4

22916-47-8

4189

Micafungin

Approved, Investigational

Phase 4

235114-32-6

477468

Clotrimazole

Approved, Vet_approved

Phase 4

23593-75-1

2812

Amoxicillin

Approved, Vet_approved

Phase 4

26787-78-0

33613

Amphotericin B

Approved, Investigational

Phase 4

1397-89-3

5280965

Posaconazole

Approved, Investigational, Vet_approved

Phase 4

171228-49-2

147912

Atorvastatin

Approved

Phase 4

134523-00-5

60823

Ursodeoxycholic acid

Approved, Investigational

Phase 4

128-13-2

31401

Cefazolin

Approved

Phase 4

25953-19-9

33255

Loperamide

Approved

Phase 4

53179-11-6

3955

Anidulafungin

Approved, Investigational

Phase 4

166663-25-8

166548

Chenodeoxycholic acid

Approved

Phase 4

474-25-9

10133

Bismuth subsalicylate

Approved, Vet_approved

Phase 4

14882-18-9

53629521 16682734

Clarithromycin

Approved

Phase 4

81103-11-9

84029

Chlorhexidine

Approved, Vet_approved, Withdrawn

Phase 4

55-56-1

2713 9552079

Coal tar

Approved

Phase 4

8007-45-2

Anastrozole

Approved, Investigational

Phase 4

120511-73-1

2187

Icodextrin

Approved, Investigational

Phase 4

337376-15-5

Propofol

Approved, Investigational, Vet_approved

Phase 4

2078-54-8

4943

Morphine

Approved, Investigational

Phase 4

57-27-2

5288826

Bupivacaine

Approved, Investigational

Phase 4

2180-92-9, 38396-39-3

2474

Ondansetron

Approved, Withdrawn

Phase 4

99614-02-5

4595

Gabapentin

Approved, Investigational

Phase 4

60142-96-3

3446

Acetaminophen

Approved

Phase 4

103-90-2

1983

Oxycodone

Approved, Illicit, Investigational

Phase 4

76-42-6

5284603

Lorazepam

Approved

Phase 4

846-49-1

3958

Cathine

Approved, Experimental, Illicit, Vet_approved, Withdrawn

Phase 4

14838-15-4, 492-39-7

131954576 4786 26934

Cyclobenzaprine

Approved

Phase 4

303-53-7

2895

Guaifenesin

Approved, Investigational, Vet_approved

Phase 4

93-14-1

3516

Hydromorphone

Approved, Illicit

Phase 4

466-99-9, 71-68-1

5284570

Hydrocodone

Approved, Illicit, Investigational

Phase 4

125-29-1

5284569

Scopolamine

Approved, Investigational

Phase 4

51-34-3

153311 3000322

Ethanol

Approved

Phase 4

64-17-5

702

Dopamine

Approved

Phase 4

62-31-7, 51-61-6

681

Bupropion

Approved

Phase 4

31677-93-7, 34841-39-9, 34911-55-2

444

Naltrexone

Approved, Investigational, Vet_approved

Phase 4

16590-41-3

5360515

Citric acid

Approved, Nutraceutical, Vet_approved

Phase 4

77-92-9

311

Folic acid

Approved, Nutraceutical, Vet_approved

Phase 4

59-30-3

6037

Cyanocobalamin

Approved, Nutraceutical

Phase 4

68-19-9

24892734 16212801 44176380

Interventional clinical trials:

(show top 50) (show all 856)

#	Name	Status	NCT ID	Phase	Drugs
1	Evaluation of the Effects of Laying Early (Between 12 and 16) a Gastric Band on the Prevention of Morbid Obesity in Late Adolescence. Randomized Checked Against Standard Management of Obesity in This Population.	Unknown status	NCT01700738	Phase 4
2	A Study of the Pharmacokinetics of Dexmedetomidine in Morbid Obesity.	Unknown status	NCT01864187	Phase 4	Dexmedetomidine
3	Correlation of Postoperative VAS Values and Body Mass Index in Patients Undergoing Abdominal Surgery: A Clinical Trial	Unknown status	NCT02017314	Phase 4	Morphine
4	Prospective Randomized Study of Effects of Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Sleeve Gastrectomy	Unknown status	NCT00667706	Phase 4
5	Laparoscopic Bariatric Surgery: Impact of the Level of Neuromuscular Blockade on Surgical Conditions - Comparison Between Moderate and Deep Neuromuscular Blockade	Unknown status	NCT02118844	Phase 4	rocuronium
6	Prospective, Pharmacokinetic Study for Determination of the Relationship Between Lean Body Weight and Anti-Xa Activity 4 Hours After Subcutaneous Injection of 5700 IU Nadroparin in Morbidly Obese Patients After Bariatric Surgery.	Unknown status	NCT02295150	Phase 4	Nadroparin
7	International, Multi Centre, Open, Prospective, Randomized Study: Banded Versus Conventional Laparoscopic Roux-en-Y (GABY)	Unknown status	NCT01015469	Phase 4
8	Preoperative Carbohydrate Loading in Bariatric Surgery - Randomized Clinical Trail	Unknown status	NCT04486079	Phase 4
9	Gut Hormones as Mediators of Different Weight Loss Responses After Roux-en-Y Gastric Bypass	Unknown status	NCT02374632	Phase 4
10	The Effect Of Vitamin D Replacement Therapy On Serum Leptin And Follicular Growth Pattern In Women With Resistant Polycystic Ovarian Syndrome	Unknown status	NCT03806036	Phase 4	Vitamin D;Clomiphene Citrate
11	Vitamin Deficiencies and Suppletion in Morbid Obesity	Completed	NCT02270749	Phase 4	Hydroxocobalamin;FitForMe vitamin B12
12	Effect of Bisphosphonate Use on Surgical Weight Loss Associated Bone Loss in Older Adults With Morbid Obesity	Completed	NCT03411902	Phase 4	Risedronate Sodium 150 MG
13	Randomized Clinical Trial Between Laparoscopic Gastric Bypass and Laparoscopic Vertical Banded Gastroplasty for Morbid Obesity	Completed	NCT01639677	Phase 4
14	A Prospective Randomized Clinical Trial Evaluating Surgical Conditions During Laparoscopic Bariatric Surgery With Deep Versus Moderate Neuromuscular Blockade	Completed	NCT02703909	Phase 4	Rocuronium
15	A Novel Preoperative Conditioning Therapy in Giant Obese Patients With the Combination of Liraglutide and a Leucine-Based Amino-Acid Infusion and Caloric Restriction	Completed	NCT02616003	Phase 4	Liraglutide
16	A Post Implantation/Post Market Evaluation of Safety and Quality of Life in Subjects Implanted With the Swedish Adjustable Gastric Band (SAGB) During Protocol CI-02-0006	Completed	NCT00543140	Phase 4
17	Effectiveness and Tolerability of Phentermine in the Reduction of Intrahepatic Fat Infiltration, Adipose Tissue and Postoperative Complications in Patients Under Bariatric Surgery	Completed	NCT03849729	Phase 4	Phentermine
18	Quadratus Lumborum II Block vs Conventional Therapy Alone For Laparoscopic Sleeve Gastrectomy	Completed	NCT04073056	Phase 4	Bupivacaine
19	A Randomized Controlled Trial for Epidural Labor Analgesia: Comparison of Dural Puncture Epidural With Standard Labor Epidural Techniques	Completed	NCT03074695	Phase 4	Dural puncture epidural (DPE);Standard Epidural (EPL)
20	Micafungin (Mycamine®) Pharmacokinetics Given as a Single Intravenous Dose to Obese Patients (MICADO).	Completed	NCT03102658	Phase 4	Micafungin
21	Population Pharmacokinetics and Pharmacodynamics of Propofol in the Morbidly Obese Patient	Completed	NCT00395681	Phase 4	Diprivan
22	Pharmacokinetics of Liposomal Amphotericin B (AmBisome®) Given Intravenously to Patients Undergoing Bariatric Surgery	Completed	NCT02320604	Phase 4	Administration of study drug
23	Pharmacokinetics of Posaconazole Given as a Single Intravenous Dose to Obese Subjects: Dosing Obese With Noxafil® Under a Trial (DONUT)	Completed	NCT03246386	Phase 4	Posaconazole Injection [Noxafil] 300mg;Posaconazole Injection [Noxafil] 400mg
24	Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin	Completed	NCT00331565	Phase 4
25	A Comparison of Cerebral Oximetry After Propofol-Based Total Intravenous Anesthesia and Sevoflurane Inhalation Anesthesia in Morbidly Obese Patients Undergoing LSG: a Prospective, Single-Blinded, Randomized, Parallel-Group Study.	Completed	NCT03946657	Phase 4	Inhalational anesthetic;Intravenous anesthetic
26	Pharmacokinetics of Intravenous Acetaminophen and Its Metabolites in Morbidly Obese Patients	Completed	NCT01764555	Phase 4	acetaminophen 2 g
27	Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function	Completed	NCT02206256	Phase 4	Omega-3 fatty acid capsules
28	CYP3A4 Metabolism Before and After Surgery Induced Weight Loss in Morbidly Obese Patients Using Midazolam as a Model Drug	Completed	NCT01519726	Phase 4	Midazolam
29	Increased Cefazolin (Ancef) Dosing for Prophylaxis During Cesarean Delivery in the Obese Population	Completed	NCT02049944	Phase 4	Cefazolin
30	Pharmacokinetics of Anidulafungin (Ecalta ®) Given Intravenously as Prophylaxis to Obese Patients With Risk of Invasive Fungal Infection Undergoing Gastric Bypass Surgery.	Completed	NCT02021123	Phase 4	Anidulafungin 100mg single dose iv
31	Effect of Bile Acids and Bile Acid Sequstrants on GLP-1 Secretion After Roux-en-Y Gastric Bypass	Completed	NCT02952963	Phase 4	Chenodeoxycholic Acid;Colesevelam
32	THE EFFECT OF HELICOBACTER PYLORI ERADICATION THERAPY TO GASTRIC WALL THICKNESS BEFORE THE LAPAROSCOPIC SLEEVE GASTRECTOMY	Completed	NCT03757650	Phase 4	Bismuth Subsalicylate
33	Comparisons of iv Ibuprofen and iv Paracetamol for Postoperative Pain Levels and Opioid Consumption During Bariatric Surgery	Completed	NCT02778958	Phase 4	paracetamol;ibuprofen
34	Clinical, Microbial and Biochemistry Evaluation of Obese Individuals Submitted to One-stage Full-mouth Disinfection. A Clinical Control Parallel Study	Completed	NCT03103204	Phase 4
35	Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot)	Completed	NCT02959853	Phase 4	Anastrazole
36	Efficacy and Tolerability of Garcinia Mangostana Extracts in the Management of Weight Loss in Severe Obese Patients	Completed	NCT02823561	Phase 4
37	Effects of Ursodeoxycholic Acid and Chenodeoxycholic Acid on GLP-1 Secretion After Roux-en-Y Gastric Bypass	Completed	NCT02340247	Phase 4	Ursodeoxycholic Acid;Chenodeoxycholic Acid
38	Effects of Chenodeoxycholic Acid and Colesevelam on GLP-1 Secretion, During a Meal, After Roux-en-Y Gastric Bypass	Completed	NCT02876484	Phase 4	Colesevelam;Chenodeoxycholic Acid
39	Pharmacokinetics (PK) of Propofol in Bariatric (Morbidly Obese) Patients	Completed	NCT01536002	Phase 4	Propofol
40	The Role of Leptin in Modulating Vascular Tone and Endothelial Function in Obese and Normal Weight Adults: A Vascular-Protective Effect of Leptin?	Completed	NCT00121433	Phase 4	leptin
41	Leptin and Ghrelin in ICU	Completed	NCT02282501	Phase 4
42	Effects of EPA Alone and Combined With Vitamin E on Blood Leptin, Adiponectin and Enzymatic Antioxidants Levels in Type II Diabetic Patients; A Randomized, Double-Blind, Placebo-Controlled Trial	Completed	NCT00817622	Phase 4
43	Effects of Non-Glucose-Based Peritoneal Dialysis Solution "EXTRANEAL" on Changes in Leptin Levels and Sympathetic Activity Induced by Conventional Glucose-Based Dialysate "DIANEAL" in Patients on Peritoneal Dialysis	Completed	NCT01228279	Phase 4
44	Multimodal Analgesia Effect on Post Surgical Patient	Recruiting	NCT04240626	Phase 4	Neurontin;Dilaudid Injectable Product;Marcaine Injectable Product;Oxycodone Hydrochloride;Hycet 7.5Mg-325Mg/15Ml Solution;Zofran Injection;Scopolamine patch;Ativan;Flexeril Oral Product;Tylenol Suspension
45	ED90 for Hyperbaric Bupivacaine in Spinal Anesthesia for Cesarean Delivery in Super Obese Parturients	Recruiting	NCT03781388	Phase 4	Bupivacaine
46	Evaluation of Propofol Dosing Based on Total Body Weight Versus Adjusted Body Weight in Obese Patients Receiving Total Intravenous Anaesthesia With Automated Closed-Loop Anaesthesia Delivery System: A Randomized Controlled Study	Recruiting	NCT05305313	Phase 4	Propofol
47	The Bioavailability and Effect on Pouch pH of Esomeprazole as Tablets or in Solution After Laparoscopic Proximal RYGB for Morbid Obesity - an Investigator Blinded Pilot Study	Not yet recruiting	NCT05320796	Phase 4
48	Use of Mysimba in Patients With Weight Regain After Bariatric Surgery	Not yet recruiting	NCT04902625	Phase 4	Naltrexone-Bupropion Combination
49	A Multicenter Study of the Effect of Recombinant Human Growth Hormone on Leptin and Cytokines in Relation to Body Composition in Pediatric Patients With Growth Failure Due to Chronic Kidney Disease (CKD)	Terminated	NCT00194961	Phase 4	Recombinant Human Growth Hormone
50	Randomized, Prospective, Double-blind Trial of PPI vs Placebo in Prevention of Gastrojejunal Strictures After Laparoscopic Roux-en-Y Gastric Bypass for Morbid Obesity	Withdrawn	NCT00361985	Phase 4	Esomeprazole

Search NIH Clinical Center for Leptin Deficiency or Dysfunction

Cochrane evidence based reviews: obesity, morbid

Sources

Genetic Tests for Leptin Deficiency or Dysfunction

Genetic tests related to Leptin Deficiency or Dysfunction:

#	Genetic test	Affiliating Genes
1	Obesity Due to Congenital Leptin Deficiency ²⁸	LEP
2	Morbid Obesity ²⁸

Sources

Anatomical Context for Leptin Deficiency or Dysfunction

Organs/tissues related to Leptin Deficiency or Dysfunction:

MalaCards : Adipocyte, Liver, Ovary, T Cells, Hypothalamus, Brain, Skeletal Muscle

Sources

Publications for Leptin Deficiency or Dysfunction

Articles related to Leptin Deficiency or Dysfunction:

(show top 50) (show all 43374)

#	Title	Authors	PMID	Year
1	Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. ⁵³ ⁶² ⁵⁷ ⁵	Licinio J...Wong ML	15070752	2004
2	A leptin missense mutation associated with hypogonadism and morbid obesity. ⁵³ ⁶² ⁵⁷ ⁵	Strobel A...Strosberg AD	9500540	1998
3	Biologically inactive leptin and early-onset extreme obesity. ⁶² ⁵⁷ ⁵	Wabitsch M...Fischer-Posovszky P	25551525	2015
4	Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. ⁶² ⁵⁷ ⁵	Gibson WT...Trussell RA	15472169	2004
5	Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. ⁶² ⁵⁷ ⁵	Farooqi IS...O'Rahilly S	12393845	2002
6	Congenital leptin deficiency is associated with severe early-onset obesity in humans. ⁶² ⁵⁷ ⁵	Montague CT...O'Rahilly S	9202122	1997
7	Leptin replacement alters brain response to food cues in genetically leptin-deficient adults. ⁵³ ⁶² ⁵⁷	Baicy K...Licinio J	17986612	2007
8	Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. ⁵³ ⁶² ⁵⁷	Ozata M...Licinio J	10523015	1999
9	Positional cloning of the mouse obese gene and its human homologue. ⁵³ ⁶² ⁵⁷	Zhang Y...Friedman JM	7984236	1994
10	Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice. ⁶² ⁵⁷	Sennello JA...Fantuzzi G	18515422	2008
11	A role for leptin in sustaining lymphopoiesis and myelopoiesis. ⁶² ⁵⁷	Claycombe K...Fraker PJ	18250302	2008
12	Leptin regulates striatal regions and human eating behavior. ⁶² ⁵⁷	Farooqi IS...Fletcher PC	17690262	2007
13	Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. ⁶² ⁵⁷	Ebihara K...Nakao K	17118991	2007
14	Is leptin an important physiological regulator of CRP? ⁶² ⁵⁷	Farooqi IS...O'Rahilly S	17206122	2007
15	Induction of leptin resistance through direct interaction of C-reactive protein with leptin. ⁶² ⁵⁷	Chen K...Zhao AZ	16582918	2006
16	Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. ⁶² ⁵⁷	Barouch LA...Hare JM	12885755	2003
17	Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. ⁶² ⁵⁷	Mancuso P...Huffnagle GB	11937559	2002
18	Partial leptin deficiency and human adiposity. ⁶² ⁵⁷	Farooqi IS...O'Rahilly S	11689931	2001
19	Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. ⁶² ⁵⁷	Hukshorn CJ...Campfield LA	11095423	2000
20	Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. ⁶² ⁵⁷	Ducy P...Karsenty G	10660043	2000
21	Effects of recombinant leptin therapy in a child with congenital leptin deficiency. ⁶² ⁵⁷	Farooqi IS...O'Rahilly S	10486419	1999
22	Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. ⁶² ⁵	Argyropoulos G...Garvey WT	9769326	1998
23	Abnormal regulation of the leptin gene in the pathogenesis of obesity. ⁶² ⁵⁷	Ioffe E...Friedman JM	9751754	1998
24	Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance. ⁶² ⁵⁷	Gloaguen I...Laufer R	9177239	1997
25	Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. ⁶² ⁵⁷	Muzzin P...Woo SL	8962136	1996
26	Peroxisome proliferator-activated receptor gamma C161-->T polymorphism and coronary artery disease. ⁵	Wang XL...Duarte N	10690291	1999
27	Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. ⁵	Ristow M...Kahn CR	9753710	1998
28	Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. ⁵⁷	Campfield LA...Burn P	7624778	1995
29	Weight-reducing effects of the plasma protein encoded by the obese gene. ⁵⁷	Halaas JL...Friedman JM	7624777	1995
30	Effects of the obese gene product on body weight regulation in ob/ob mice. ⁵⁷	Pelleymounter MA...Collins F	7624776	1995
31	Genetics. In search of a satiety factor. ⁵⁷	Rink TJ	7984230	1994
32	Obesity genes: beneficial effects in heterozygous mice. ⁵⁷	Coleman DL	760211	1979
33	Thermogenic defect in pre-obese ob/ob mice. ⁵⁷	Trayhurn P...James WP	840297	1977
34	Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? ⁵⁷	NEEL JV	13937884	1962
35	Obese, a new mutation in the house mouse. ⁵⁷	INGALLS AM...SNELL GD	14824537	1950
36	Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. ⁵³ ⁶²	Sell H...Clement K	20375212	2010
37	The relationships between IGF-1 and CRP, NO, leptin, and adiponectin during weight loss in the morbidly obese. ⁵³ ⁶²	Pardina E...Peinado-Onsurbe J	20195789	2010
38	Rates of lipid fluxes in adipose tissue in vivo after a mixed meal in morbid obesity. ⁵³ ⁶²	Mitrou P...Dimitriadis G	20084071	2010
39	Metabolic syndrome and insulin resistance in subjects with morbid obesity. ⁵³ ⁶²	Soverini V...Marchesini G	19841991	2010
40	Estradiol and metabolic syndrome in older italian men: The InCHIANTI Study. ⁵³ ⁶²	Maggio M...Ferrucci L	19059904	2010
41	Leptin-signaling pathways and leptin resistance. ⁵³ ⁶²	Munzberg H	19955780	2010
42	Ala54Thr polymorphism of fatty acid binding protein 2, role on insulin resistance and cardiovascular risk factors in presurgical morbid obesity patients. ⁵³ ⁶²	de Luis DA...Romero E	19475463	2009
43	Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes. ⁵³ ⁶²	Kiewiet RM...van der Lely AJ	19628651	2009
44	Inflammatory mediators in morbidly obese subjects: associations with glucose abnormalities and changes after oral glucose. ⁵³ ⁶²	Hofso D...Hjelmesaeth J	19542241	2009
45	A novel function of intestinal gluconeogenesis: central signaling in glucose and energy homeostasis. ⁵³ ⁶²	Mithieux G	19647621	2009
46	[Study of the relationship between adiponectin, interleukin-18, ghrelin and bone mineral density in morbidly obese women after gastric bypass]. ⁵³ ⁶²	Vilarrasa N...Vendrell J	19883895	2009
47	Rates of glucose uptake in adipose tissue and muscle in vivo after a mixed meal in women with morbid obesity. ⁵³ ⁶²	Mitrou P...Dimitriadis G	19435828	2009
48	Maternal obesity and markers of inflammation in pregnancy. ⁵³ ⁶²	Madan JC...Dammann O	19505831	2009
49	Adipocyte fatty acid-binding protein as a determinant of insulin sensitivity in morbid-obese women. ⁵³ ⁶²	Simon I...Vendrell J	19197257	2009
50	The effect of intragastric balloon on plasma ghrelin, leptin, and adiponectin levels in patients with morbid obesity. ⁵³ ⁶²	Konopko-Zubrzycka M...Dabrowski A	19258408	2009

Sources

Genes for Leptin Deficiency or Dysfunction

Genes related to Leptin Deficiency or Dysfunction (3 elite genes):

(show top 50) (show all 75)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	LEP	Leptin	Protein Coding	1700.08	Molecular basis known ⁵⁷ Pathogenic ⁵ Causative germline mutation ⁵⁸ Causative variation ⁷³ Genetic Tests ²⁸ Likely pathogenic ⁵ DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	9202122 9500540 12393845 (more) 15070752 15472169 25551525 26567097 16354527 9150718 19396752 9537324 9545018 10665337 10102052 10981034 11148335 11836325 17986612 11062083 9226485 14694209 11889184 11276500 10523015 15229336 19433638 19258408 19505831 18854428 17728393 12270921 11824506 19127895 17059747 15130222 10394277 15802059 12647279 20195789 12519870 11820995 16687021 14715846 15713712 19050673 19955780 7984236
2	PPARG	Peroxisome Proliferator Activated Receptor Gamma	Protein Coding	411.25	Pathogenic ⁵ DISEASES inferred ¹⁴ ¹⁴	9753710 10690291
3	UCP3	Uncoupling Protein 3	Protein Coding	405.31	Pathogenic ⁵ DISEASES inferred ¹⁴	9769326
4	MC4R	Melanocortin 4 Receptor	Protein Coding	23.48	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	10903341 17941900 10903343 (more) 10196693 11443223
5	INS	Insulin	Protein Coding	22.22	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	19841991 16687020 17954414 (more) 19628651 16354527 1563582 15507518 19435828 10665337 12150695 1640847 15128628 17509385 18398808 16767306 15235324 9496556 1737857 18401671 18159925 12957694 12429873 19059904 16756729 16117191 15946459 14747301 12687350 9925352 8982898 16801578 15811276 16901360 15809999 12861276 11787371 9075607 8969285 16989707 17059747 16006297 19150743 17608262 14679177 9551249 8581772 19475463 19647621 19197257 17929210 17654134 11820995 11820033 11062083 20375212 20084071 19327608 18713823 16684123 17264851 16989703 11756334 17459653 17443025 14715846 15527630
6	GHRL	Ghrelin And Obestatin Prepropeptide	Protein Coding	21.94	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	17443025 19628651 15057669 (more) 16687021 12379512 15229336 19883895 18516524
7	LEPR	Leptin Receptor	Protein Coding	21.02	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	9537324 9545018 11276500 (more) 12270921
8	ADIPOQ	Adiponectin, C1Q And Collagen Domain Containing	Protein Coding	20.4	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	18777458 16687021 19258408 (more) 15830179 19883895 16901360 19542241 19433638 15229336
9	PYY	Peptide YY	Protein Coding	19.81	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	15855352 17443025
10	GCG	Glucagon	Protein Coding	19.18	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	15002062
11	MC3R	Melanocortin 3 Receptor	Protein Coding	19.07	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	12532156
12	ADRB3	Adrenoceptor Beta 3	Protein Coding	16.35	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	8968849 7609752 8968850 (more) 9416435 15479221
13	RETN	Resistin	Protein Coding	15.8	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	15229336
14	CCK	Cholecystokinin	Protein Coding	15.62	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	17443025
15	AGRP	Agouti Related Neuropeptide	Protein Coding	14.59	DISEASES inferred ¹⁴ ¹⁴
16	NPY	Neuropeptide Y	Protein Coding	13.68	DISEASES inferred ¹⁴ ¹⁴
17	POMC	Proopiomelanocortin	Protein Coding	13.48	DISEASES inferred ¹⁴ ¹⁴
18	SIM1	SIM BHLH Transcription Factor 1	Protein Coding	12.7	DISEASES inferred ¹⁴ ¹⁴
19	LPL	Lipoprotein Lipase	Protein Coding	12.54	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	15866227
20	PCSK1	Proprotein Convertase Subtilisin/Kexin Type 1	Protein Coding	12.48	DISEASES inferred ¹⁴ ¹⁴
21	HCRT	Hypocretin Neuropeptide Precursor	Protein Coding	12.34	DISEASES inferred ¹⁴ ¹⁴ Novoseek inferred ⁵³	15970339
22	SH2B1	SH2B Adaptor Protein 1	Protein Coding	12.26	DISEASES inferred ¹⁴ ¹⁴
23	CARTPT	CART Prepropeptide	Protein Coding	11.72	DISEASES inferred ¹⁴ ¹⁴
24	FTO	FTO Alpha-Ketoglutarate Dependent Dioxygenase	Protein Coding	11.63	DISEASES inferred ¹⁴ ¹⁴
25	IL6	Interleukin 6	Protein Coding	11.63	DISEASES inferred ¹⁴ ¹⁴
26	UCP1	Uncoupling Protein 1	Protein Coding	11.58	DISEASES inferred ¹⁴ ¹⁴
27	SOCS3	Suppressor Of Cytokine Signaling 3	Protein Coding	11.56	DISEASES inferred ¹⁴ ¹⁴
28	IGF1	Insulin Like Growth Factor 1	Protein Coding	11.32	DISEASES inferred ¹⁴ ¹⁴
29	IAPP	Islet Amyloid Polypeptide	Protein Coding	11.22	DISEASES inferred ¹⁴ ¹⁴
30	STAT3	Signal Transducer And Activator Of Transcription 3	Protein Coding	11.03	DISEASES inferred ¹⁴ ¹⁴
31	CRP	C-Reactive Protein	Protein Coding	11.02	DISEASES inferred ¹⁴ ¹⁴
32	KISS1	KiSS-1 Metastasis Suppressor	Protein Coding	10.84	DISEASES inferred ¹⁴ ¹⁴
33	PTPN1	Protein Tyrosine Phosphatase Non-Receptor Type 1	Protein Coding	10.82	DISEASES inferred ¹⁴ ¹⁴
34	TRH	Thyrotropin Releasing Hormone	Protein Coding	10.79	DISEASES inferred ¹⁴ ¹⁴
35	NAMPT	Nicotinamide Phosphoribosyltransferase	Protein Coding	10.77	DISEASES inferred ¹⁴ ¹⁴
36	FGF21	Fibroblast Growth Factor 21	Protein Coding	10.76	DISEASES inferred ¹⁴ ¹⁴
37	GHSR	Growth Hormone Secretagogue Receptor	Protein Coding	10.72	DISEASES inferred ¹⁴ ¹⁴
38	BDNF	Brain Derived Neurotrophic Factor	Protein Coding	10.7	DISEASES inferred ¹⁴ ¹⁴
39	JAK2	Janus Kinase 2	Protein Coding	10.68	DISEASES inferred ¹⁴ ¹⁴
40	TNF	Tumor Necrosis Factor	Protein Coding	10.65	DISEASES inferred ¹⁴ ¹⁴
41	ADIPOR2	Adiponectin Receptor 2	Protein Coding	10.63	DISEASES inferred ¹⁴ ¹⁴
42	IRS1	Insulin Receptor Substrate 1	Protein Coding	10.62	DISEASES inferred ¹⁴ ¹⁴
43	ADIPOR1	Adiponectin Receptor 1	Protein Coding	10.52	DISEASES inferred ¹⁴ ¹⁴
44	SLC2A4	Solute Carrier Family 2 Member 4	Protein Coding	10.44	DISEASES inferred ¹⁴ ¹⁴
45	MAGEL2	MAGE Family Member L2	Protein Coding	10.26	DISEASES inferred ¹⁴ ¹⁴
46	SREBF1	Sterol Regulatory Element Binding Transcription Factor 1	Protein Coding	10.23	DISEASES inferred ¹⁴ ¹⁴
47	GLP1R	Glucagon Like Peptide 1 Receptor	Protein Coding	10.21	DISEASES inferred ¹⁴ ¹⁴
48	PPARA	Peroxisome Proliferator Activated Receptor Alpha	Protein Coding	10.2	DISEASES inferred ¹⁴ ¹⁴
49	GNRH1	Gonadotropin Releasing Hormone 1	Protein Coding	10.2	DISEASES inferred ¹⁴ ¹⁴
50	NTRK2	Neurotrophic Receptor Tyrosine Kinase 2	Protein Coding	10.18	DISEASES inferred ¹⁴ ¹⁴

Sources

Variations for Leptin Deficiency or Dysfunction

ClinVar genetic disease variations for Leptin Deficiency or Dysfunction:

⁵ (show top 50) (show all 78)

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	PPARG	NM_138711.6(PPARG):c.248C>A (p.Pro83Gln)	SNV	Pathogenic	8130	rs1800571	GRCh37: 3:12422848-12422848 GRCh38: 3:12381349-12381349
2	LEP	NM_000230.3(LEP):c.313C>T (p.Arg105Trp)	SNV	Pathogenic	13987	rs104894023	GRCh37: 7:127894625-127894625 GRCh38: 7:128254572-128254572
3	LEP	NM_000230.3(LEP):c.298G>T (p.Asp100Tyr)	SNV	Pathogenic	162430	rs724159998	GRCh37: 7:127894610-127894610 GRCh38: 7:128254557-128254557
4	LEP	NM_000230.3(LEP):c.398del (p.Gly133fs)	DEL	Pathogenic	13986		GRCh37: 7:127894705-127894705 GRCh38: 7:128254652-128254652
5	UCP3	NM_003356.4(UCP3):c.824+1G>A	SNV	Pathogenic	7578	rs45476292	GRCh37: 11:73714871-73714871 GRCh38: 11:74003826-74003826
6	LEP	NM_000230.3(LEP):c.461T>C (p.Leu154Pro)	SNV	Likely Pathogenic	448905	rs1554394014	GRCh37: 7:127894773-127894773 GRCh38: 7:128254720-128254720
7	LEP	NM_000230.3(LEP):c.*1318G>C	SNV	Uncertain Significance	908787	rs200129463	GRCh37: 7:127896134-127896134 GRCh38: 7:128256081-128256081
8	LEP	NM_000230.3(LEP):c.*1369G>T	SNV	Uncertain Significance	908788	rs1482418354	GRCh37: 7:127896185-127896185 GRCh38: 7:128256132-128256132
9	LEP	NM_000230.3(LEP):c.*1422A>T	SNV	Uncertain Significance	908789	rs1795337523	GRCh37: 7:127896238-127896238 GRCh38: 7:128256185-128256185
10	LEP	NM_000230.3(LEP):c.*2110G>T	SNV	Uncertain Significance	908851	rs187235717	GRCh37: 7:127896926-127896926 GRCh38: 7:128256873-128256873
11	LEP	NM_000230.3(LEP):c.-14T>G	SNV	Uncertain Significance	909528	rs1795280375	GRCh37: 7:127892058-127892058 GRCh38: 7:128252005-128252005
12	LEP	NM_000230.3(LEP):c.*373G>A	SNV	Uncertain Significance	909587	rs183801334	GRCh37: 7:127895189-127895189 GRCh38: 7:128255136-128255136
13	LEP	NM_000230.3(LEP):c.*1579G>A	SNV	Uncertain Significance	909642	rs200802392	GRCh37: 7:127896395-127896395 GRCh38: 7:128256342-128256342
14	LEP	NM_000230.3(LEP):c.*1637A>G	SNV	Uncertain Significance	909643	rs780861433	GRCh37: 7:127896453-127896453 GRCh38: 7:128256400-128256400
15	LEP	NM_000230.3(LEP):c.*2245C>G	SNV	Uncertain Significance	909706	rs201052331	GRCh37: 7:127897061-127897061 GRCh38: 7:128257008-128257008
16	LEP	NM_000230.3(LEP):c.*2263G>A	SNV	Uncertain Significance	909707	rs1795349651	GRCh37: 7:127897079-127897079 GRCh38: 7:128257026-128257026
17	LEP	NM_000230.3(LEP):c.*2437C>T	SNV	Uncertain Significance	909708	rs536449594	GRCh37: 7:127897253-127897253 GRCh38: 7:128257200-128257200
18	LEP	NM_000230.3(LEP):c.143C>T (p.Thr48Met)	SNV	Uncertain Significance	910457	rs770247453	GRCh37: 7:127892214-127892214 GRCh38: 7:128252161-128252161
19	LEP	NM_000230.3(LEP):c.*653A>C	SNV	Uncertain Significance	910510	rs201341056	GRCh37: 7:127895469-127895469 GRCh38: 7:128255416-128255416
20	LEP	NM_000230.3(LEP):c.*750G>C	SNV	Uncertain Significance	910511	rs977939827	GRCh37: 7:127895566-127895566 GRCh38: 7:128255513-128255513
21	LEP	NM_000230.3(LEP):c.*781G>C	SNV	Uncertain Significance	910512	rs70940808	GRCh37: 7:127895597-127895597 GRCh38: 7:128255544-128255544
22	LEP	NM_000230.3(LEP):c.*1738G>A	SNV	Uncertain Significance	910572	rs201949587	GRCh37: 7:127896554-127896554 GRCh38: 7:128256501-128256501
23	LEP	NM_000230.3(LEP):c.*1749T>C	SNV	Uncertain Significance	910573	rs1483827030	GRCh37: 7:127896565-127896565 GRCh38: 7:128256512-128256512
24	LEP	NM_000230.3(LEP):c.*1825T>C	SNV	Uncertain Significance	910574	rs199792491	GRCh37: 7:127896641-127896641 GRCh38: 7:128256588-128256588
25	LEP	NM_000230.3(LEP):c.*962T>G	SNV	Uncertain Significance	911752	rs1795330798	GRCh37: 7:127895778-127895778 GRCh38: 7:128255725-128255725
26	LEP	NM_000230.3(LEP):c.*1124G>A	SNV	Uncertain Significance	911753	rs3750034	GRCh37: 7:127895940-127895940 GRCh38: 7:128255887-128255887
27	LEP	NM_000230.3(LEP):c.*1185C>T	SNV	Uncertain Significance	911754	rs200556203	GRCh37: 7:127896001-127896001 GRCh38: 7:128255948-128255948
28	LEP	NM_000230.3(LEP):c.*1886T>G	SNV	Uncertain Significance	911808	rs201604408	GRCh37: 7:127896702-127896702 GRCh38: 7:128256649-128256649
29	LEP	NM_000230.3(LEP):c.*2800G>A	SNV	Uncertain Significance	911852	rs1378129983	GRCh37: 7:127897616-127897616 GRCh38: 7:128257563-128257563
30	LEP	NM_000230.3(LEP):c.21C>T (p.Cys7=)	SNV	Uncertain Significance	358815	rs201523305	GRCh37: 7:127892092-127892092 GRCh38: 7:128252039-128252039
31	LEP	NM_000230.3(LEP):c.*57C>T	SNV	Uncertain Significance	911681	rs1795318328	GRCh37: 7:127894873-127894873 GRCh38: 7:128254820-128254820
32	LEP	NM_000230.3(LEP):c.*33C>T	SNV	Uncertain Significance	911680	rs62481073	GRCh37: 7:127894849-127894849 GRCh38: 7:128254796-128254796
33	LEP	NM_000230.3(LEP):c.436G>T (p.Ala146Ser)	SNV	Uncertain Significance	911679	rs1795315989	GRCh37: 7:127894748-127894748 GRCh38: 7:128254695-128254695
34	LEP	NM_000230.3(LEP):c.*2503C>T	SNV	Uncertain Significance	910630	rs200431904	GRCh37: 7:127897319-127897319 GRCh38: 7:128257266-128257266
35	LEP	NM_000230.3(LEP):c.*2738G>A	SNV	Uncertain Significance	358852	rs201644572	GRCh37: 7:127897554-127897554 GRCh38: 7:128257501-128257501
36	LEP	NM_000230.3(LEP):c.*2015C>A	SNV	Uncertain Significance	358840	rs28959471	GRCh37: 7:127896831-127896831 GRCh38: 7:128256778-128256778
37	LEP	NM_000230.3(LEP):c.*992G>T	SNV	Uncertain Significance	358830	rs886061976	GRCh37: 7:127895808-127895808 GRCh38: 7:128255755-128255755
38	LEP	NM_000230.3(LEP):c.*785A>G	SNV	Uncertain Significance	358829	rs114834517	GRCh37: 7:127895601-127895601 GRCh38: 7:128255548-128255548
39	LEP	NM_000230.3(LEP):c.*150G>A	SNV	Uncertain Significance	358822	rs28954115	GRCh37: 7:127894966-127894966 GRCh38: 7:128254913-128254913
40	LEP	NM_000230.3(LEP):c.*2224G>A	SNV	Uncertain Significance	358843	rs28959472	GRCh37: 7:127897040-127897040 GRCh38: 7:128256987-128256987
41	LEP	NM_000230.3(LEP):c.53A>G (p.Tyr18Cys)	SNV	Uncertain Significance	910456	rs148407750	GRCh37: 7:127892124-127892124 GRCh38: 7:128252071-128252071
42	LEP	NM_000230.3(LEP):c.165G>A (p.Gln55=)	SNV	Uncertain Significance	724209	rs138908051	GRCh37: 7:127894477-127894477 GRCh38: 7:128254424-128254424
43	LEP	NM_000230.3(LEP):c.*204C>T	SNV	Uncertain Significance	358823	rs113405088	GRCh37: 7:127895020-127895020 GRCh38: 7:128254967-128254967
44	LEP	NM_000230.3(LEP):c.*360G>A	SNV	Uncertain Significance	358825	rs200748706	GRCh37: 7:127895176-127895176 GRCh38: 7:128255123-128255123
45	LEP	NM_000230.3(LEP):c.*1428C>A	SNV	Uncertain Significance	358835	rs76601079	GRCh37: 7:127896244-127896244 GRCh38: 7:128256191-128256191
46	LEP	NM_000230.3(LEP):c.144+15C>T	SNV	Uncertain Significance	358816	rs776318015	GRCh37: 7:127892230-127892230 GRCh38: 7:128252177-128252177
47	LEP	NM_000230.3(LEP):c.*366A>T	SNV	Uncertain Significance	358826	rs28954118	GRCh37: 7:127895182-127895182 GRCh38: 7:128255129-128255129
48	LEP	NM_000230.3(LEP):c.*1549T>C	SNV	Uncertain Significance	358836	rs201701012	GRCh37: 7:127896365-127896365 GRCh38: 7:128256312-128256312
49	LEP	NM_000230.3(LEP):c.*1010C>A	SNV	Uncertain Significance	358831	rs138289049	GRCh37: 7:127895826-127895826 GRCh38: 7:128255773-128255773
50	LEP	NM_000230.3(LEP):c.*2822dup	DUP	Uncertain Significance	358854	rs56247456	GRCh37: 7:127897620-127897621 GRCh38: 7:128257567-128257568

UniProtKB/Swiss-Prot genetic disease variations for Leptin Deficiency or Dysfunction:

⁷³

#	Symbol	AA change	Variation ID	SNP ID
1	LEP	p.Arg105Trp	VAR_008094	rs104894023
2	LEP	p.Asp100Tyr	VAR_075144	rs724159998

Sources

Expression for Leptin Deficiency or Dysfunction

Genes differentially expressed in tissues of Leptin Deficiency or Dysfunction patients vs. healthy controls: ³⁵

#	Gene	Description	Tissue	Up/Dn	Fold Change (log2)	P value
1	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	Skeletal Muscle	-	5.09	0.006
2	SLN	sarcolipin	Skeletal Muscle	-	4.64	0.007

Search GEO for disease gene expression data for Leptin Deficiency or Dysfunction.

Sources

Pathways for Leptin Deficiency or Dysfunction

Pathways related to Leptin Deficiency or Dysfunction according to GeneCards Suite gene sharing:

(show all 25)

#	Super pathways	Score	Top Affiliating Genes
1	GPCR downstream signalling ⁶⁶ Show member pathways G alpha (i) signalling events ⁶⁶ G alpha (q) signalling events ⁶⁶ Signaling by GPCR ⁶⁶	13.49	ADRB3 CCK GCG GHRL MC3R MC4R
2	Signal Transduction ⁶⁶	13.48	ADRB3 CCK GCG GHRL INS LEP
3	Class A/1 (Rhodopsin-like receptors) ⁶⁶ Show member pathways GPCR ligand binding ⁶⁶ GPCRs, class A rhodopsin-like ⁷⁴ Peptide GPCRs ⁷⁴ Peptide ligand-binding receptors ⁶⁶	13.28	PYY POMC NPY MC4R MC3R GHRL
4	Glucose / Energy Metabolism ³	12.46	UCP3 PPARG INS GCG ADIPOQ
5	PPARA activates gene expression ⁶⁶ Show member pathways Regulation of lipid metabolism by PPARalpha ⁶⁶ Transcriptional regulation of white adipocyte differentiation ⁶⁶	12.42	PPARG LPL LEP ADIPOQ
6	G alpha (s) signalling events ⁶⁶ Show member pathways Defective ACTH causes obesity and POMCD ⁶⁶	12.06	POMC MC4R MC3R GCG ADRB3
7	AMP-activated protein kinase signaling ⁷⁴ Show member pathways AMPK Signaling Pathway ⁶⁷ Leptin and adiponectin ⁷⁴	12.04	LEPR LEP INS ADIPOQ
8	Peptide hormone metabolism ⁶⁶ Show member pathways Glycoprotein hormones ⁶⁶ Metabolism of Angiotensinogen to Angiotensins ⁶⁶ Metabolism of Angiotensinogen to Angiotensins ⁷⁴ Peptide hormone biosynthesis ⁶⁶ Synthesis, secretion, and deacylation of Ghrelin ⁶⁶ thyroid hormone biosynthesis ⁶¹	12.03	POMC PCSK1 LEP INS GHRL GCG
9	FOXO-mediated transcription ⁶⁶ Show member pathways FOXO-mediated transcription of cell cycle genes ⁶⁶ FOXO-mediated transcription of cell death genes ⁶⁶ FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes ⁶⁶ Regulation of FOXO transcriptional activity by acetylation ⁶⁶ Regulation of localization of FOXO transcription factors ⁶⁶	12	RETN POMC NPY INS AGRP
10	Thermogenesis ⁷⁴ Show member pathways mitochondrial L-carnitine shuttle ⁶¹	11.85	PPARG GCG ADRB3
11	Adipogenesis ⁷⁴	11.75	RETN PPARG LPL LEP INS ADIPOQ
12	Mesenchymal Stem Cells and Lineage-specific Markers ⁶⁵	11.74	PPARG LPL LEP INS ADIPOQ
13	PPAR signaling pathway ⁷⁴ Show member pathways FABP4 in ovarian cancer ⁷⁴ Fatty acid transporters ⁷⁴	11.73	PPARG LPL ADIPOQ
14	Prader-Willi and Angelman syndrome ⁷⁴	11.56	GHRL INS PCSK1 POMC
15	Incretin synthesis, secretion, and inactivation ⁶⁶ Show member pathways Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) ⁶⁶ Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) ⁶⁶	11.54	PCSK1 LEP GCG
16	Signaling events mediated by PTP1B ⁶¹	11.43	LEPR LEP INS
17	Nonalcoholic fatty liver disease ⁷⁴	11.37	LEPR LEP INS ADIPOQ
18	Thyroid hormones production and peripheral downstream signaling effects ⁷⁴	11.35	PPARG POMC NPY MC4R AGRP ADRB3
19	Development_Leptin signaling via JAK/STAT and MAPK cascades ²² Show member pathways phospho-PLA2 pathway ⁶⁶	11.21	POMC LEPR LEP
20	Leptin-insulin signaling overlap ⁷⁴ Show member pathways Signaling by Leptin ⁶⁶	11.17	LEPR LEP INS
21	Differentiation of white and brown adipocyte ⁷⁴	11.11	PPARG LEP ADIPOQ
22	Transcription factor regulation in adipogenesis ⁷⁴	11.04	PPARG LEP ADIPOQ
23	Syndecan-3-mediated signaling events ⁶¹	10.99	POMC MC4R AGRP
24	Antipsychotics Pathway (Metabolic Side Effects), Pharmacodynamics ⁶⁰	10.58	PYY POMC NPY MC4R LEPR LEP
25	SCFA and skeletal muscle substrate metabolism ⁷⁴	10.38	PYY GCG

Sources

GO Terms for Leptin Deficiency or Dysfunction

Cellular components related to Leptin Deficiency or Dysfunction according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	extracellular region	GO:0005576	10.25	RETN PYY POMC NPY LPL LEPR
2	extracellular space	GO:0005615	9.74	RETN PYY POMC PCSK1 NPY LPL
3	secretory granule lumen	GO:0034774	9.65	GCG GHRL INS PCSK1 POMC

Biological processes related to Leptin Deficiency or Dysfunction according to GeneCards Suite gene sharing:

(show all 38)

#	Name	GO ID	Score	Top Affiliating Genes
1	signal transduction	GO:0007165	10.5	ADIPOQ ADRB3 CCK INS LEP MC3R
2	positive regulation of MAPK cascade	GO:0043410	10.26	LEP INS GHRL ADRB3
3	aging	GO:0007568	10.25	ADRB3 NPY RETN UCP3
4	neuropeptide signaling pathway	GO:0007218	10.19	AGRP NPY POMC PYY
5	positive regulation of cold-induced thermogenesis	GO:0120162	10.18	ADIPOQ ADRB3 GHRL LEP LEPR
6	adenylate cyclase-activating G protein-coupled receptor signaling pathway	GO:0007189	10.17	ADRB3 GCG MC3R MC4R
7	glucose metabolic process	GO:0006006	10.16	ADIPOQ GHRL INS LEP
8	G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	GO:0007187	10.15	NPY MC3R ADRB3
9	response to glucocorticoid	GO:0051384	10.14	UCP3 PCSK1 ADIPOQ
10	generation of precursor metabolites and energy	GO:0006091	10.12	POMC ADRB3 ADIPOQ
11	hormone-mediated signaling pathway	GO:0009755	10.11	PPARG GHRL AGRP
12	response to activity	GO:0014823	10.11	UCP3 LEP GCG ADIPOQ
13	regulation of blood pressure	GO:0008217	10.11	PPARG POMC NPY MC3R LEP
14	response to insulin	GO:0032868	10.1	AGRP LEP MC4R RETN UCP3
15	response to nutrient	GO:0007584	10.09	ADIPOQ LEP PPARG UCP3
16	adenylate cyclase-modulating G protein-coupled receptor signaling pathway	GO:0007188	10.07	MC4R MC3R GCG ADRB3
17	negative regulation of gluconeogenesis	GO:0045721	10.04	LEPR INS ADIPOQ
18	response to cold	GO:0009409	10.04	UCP3 PPARG LPL ADRB3
19	eating behavior	GO:0042755	10.03	LEP CCK AGRP ADRB3
20	leptin-mediated signaling pathway	GO:0033210	9.97	LEPR LEP
21	negative regulation of lipid storage	GO:0010888	9.97	PPARG LEP
22	regulation of metabolic process	GO:0019222	9.97	MC4R MC3R LEP
23	positive regulation of adipose tissue development	GO:1904179	9.96	PPARG GHRL
24	regulation of bone remodeling	GO:0046850	9.93	LEPR LEP
25	response to nutrient levels	GO:0031667	9.93	ADIPOQ GHRL LEP PCSK1
26	bone growth	GO:0098868	9.92	LEPR LEP
27	energy reserve metabolic process	GO:0006112	9.92	MC4R LEPR LEP ADRB3
28	positive regulation of fatty acid metabolic process	GO:0045923	9.91	PPARG ADIPOQ
29	positive regulation of eating behavior	GO:1904000	9.91	NPY GHRL
30	positive regulation of appetite	GO:0032100	9.9	NPY GHRL
31	response to melanocyte-stimulating hormone	GO:1990680	9.88	POMC MC4R
32	negative regulation of feeding behavior	GO:2000252	9.85	RETN MC4R INS
33	positive regulation of feeding behavior	GO:2000253	9.83	GHRL AGRP
34	negative regulation of acute inflammatory response	GO:0002674	9.82	PPARG INS
35	regulation of feeding behavior	GO:0060259	9.8	MC4R MC3R LEPR AGRP
36	adult feeding behavior	GO:0008343	9.76	AGRP GHRL LEP NPY
37	feeding behavior	GO:0007631	9.65	PYY NPY MC4R GCG AGRP
38	glucose homeostasis	GO:0042593	9.47	PPARG POMC LEPR LEP INS GCG

Molecular functions related to Leptin Deficiency or Dysfunction according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	signaling receptor binding	GO:0005102	9.97	ADIPOQ AGRP GCG LEP LPL NPY
2	peptide hormone binding	GO:0017046	9.93	MC4R MC3R LEPR
3	G protein-coupled receptor binding	GO:0001664	9.86	PYY POMC NPY GHRL
4	peptide hormone receptor binding	GO:0051428	9.78	LEP CCK
5	melanocortin receptor activity	GO:0004977	9.73	MC4R MC3R
6	type 1 melanocortin receptor binding	GO:0070996	9.71	POMC AGRP
7	neuropeptide Y receptor binding	GO:0031841	9.67	PYY NPY
8	melanocyte-stimulating hormone receptor activity	GO:0004980	9.62	MC4R MC3R
9	hormone activity	GO:0005179	9.6	RETN PYY POMC NPY LEP INS
10	neuropeptide hormone activity	GO:0005184	9.56	PYY NPY CCK AGRP