|
Obesity
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
|
|
|
|
Obesity
|
1.000 |
Biomarker
|
disease |
HPO |
|
|
|
|
Obesity
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
|
|
|
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Molecular screening of the human melanocortin-4 receptor gene: identification of a missense variant showing no association with obesity, plasma glucose, or insulin.
|
9267995 |
1997 |
|
Obesity
|
1.000 |
Biomarker
|
disease |
MGD |
Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R.
|
9019399 |
1997 |
|
Obesity
|
1.000 |
Biomarker
|
disease |
BEFREE |
Recent studies in animal models elucidated a central role of alpha-MSH in the regulation of food intake by activation of the brain melanocortin-4-receptor (MC4-R; refs 3-5) and the linkage of human obesity to chromosome 2 in close proximity to the POMC locus, led to the proposal of an association of POMC with human obesity.
|
9620771 |
1998 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Most of these obesity disorders exhibit a distinct phenotype with varying degrees of hypothalamic and pituitary dysfunction and a recessive inheritance, whereas MC4-R mutation has a nonsyndromic phenotype with dominant inheritance.
|
10508193 |
1999 |
|
Obesity
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
Both the index patient (BMI 42.06 kg/m2, height 171 cm, age 19.6 years) and her mother (BMI 37.55 kg/m2, height 164 cm, age 42.5 years) were heterozygous for the deletion. b) A nonsense mutation at position 35 of the MC4-R was detected in two obese probands (BMI 31.29 kg/m2 and BMI 45.91 kg/m2).
|
10199800 |
1999 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In conclusion, our data fully support the etiologic role of MC4-R haploinsufficiency mutations in obesity.
|
10577903 |
1999 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
UNIPROT |
Both the index patient (BMI 42.06 kg/m2, height 171 cm, age 19.6 years) and her mother (BMI 37.55 kg/m2, height 164 cm, age 42.5 years) were heterozygous for the deletion. b) A nonsense mutation at position 35 of the MC4-R was detected in two obese probands (BMI 31.29 kg/m2 and BMI 45.91 kg/m2).
|
10199800 |
1999 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
These results suggest that mutations including V103I in the MC4R gene are not a major cause of obesity or diabetes in Japanese.
|
11246450 |
1999 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Thus, unlike the obesity-associated MC4R truncation mutants, the polymorphisms of MC4R are unlikely to be contributors to human obesity.
|
10585465 |
1999 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, our results also suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a common cause of obesity in the population studied, given the low frequency of functionally significant mutations.
|
10078568 |
1999 |
|
Obesity
|
1.000 |
Biomarker
|
disease |
BEFREE |
This supports the hypothesis that the MC4R gene product is haplosufficient and the involvement of MC4R in obesity may reflect a dominant negative effect.
|
10598807 |
1999 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans.
|
10199800 |
1999 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Recently, Pomc knockout mice were generated and shown to develop hyperphagia and obesity with a time-course and severity comparable to MC4-R knockout mice, whereas daily administration of a stable alpha-melanocyte stimulating hormone analogue reversed this effect.
|
10885325 |
2000 |
|
Obesity
|
1.000 |
Biomarker
|
disease |
BEFREE |
This variable expressivity of MC4-R-associated obesity is not due to variations in genes for alpha-MSH or AGRP.
|
10903341 |
2000 |
|
Obesity
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency.
|
10903343 |
2000 |
|
Obesity
|
1.000 |
Biomarker
|
disease |
MGD |
Disproportionate inhibition of feeding in A(y) mice by certain stressors: a cautionary note.
|
10971147 |
2000 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Thus MC4R mutations result in a syndrome of hyperphagic obesity in humans that can present with either dominant or recessive patterns of inheritance.
|
10903343 |
2000 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In our study, we addressed the hypothesis that a G-->A substitution at codon 103 (Val-103Ile) of the MC4R gene influences abdominal obesity, insulin, glucose, and lipid metabolism as well as circulating hormones, including salivary cortisol.
|
11692184 |
2001 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
UNIPROT |
Clinical and laboratory features were similar in the obese children with and without an MC4R mutation.
|
11487744 |
2001 |
|
Obesity
|
1.000 |
GeneticVariation
|
disease |
UNIPROT |
As part of our ongoing project entitled 'Turkish Obesity Genome Study' we determined the nucleotide sequence of the entire coding region of the MC4R gene in 40 morbidly obese subjects from independent families.
|
11443223 |
2001 |
|
Obesity
|
1.000 |
Biomarker
|
disease |
BEFREE |
The identification of the genetic defect underlying the obese phenotype of the viable yellow mouse, ectopic overexpression of the agouti protein which acts as antagonist at the melanocortin-4 receptor, together with the demonstration that the brain melanocortin system was one major downstream effector pathway of leptin signaling has put forward melanocortin receptors as drug targets for obesity.
|
11704425 |
2001 |
|
Obesity
|
1.000 |
Biomarker
|
disease |
MGD |
Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat.
|
11369941 |
2001 |