{{Rsnum
|rsid=2229616
|Gene=MC4R
|Chromosome=18
|position=60372043
|Orientation=minus
|ReferenceAllele=G
|MissenseAllele=A
|GMAF=0.01928
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=MC4R
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 0.0 | 1.8 | 98.2
| HCB | 0.0 | 5.8 | 94.2
| JPT | 0.0 | 0.9 | 99.1
| YRI | 0.0 | 3.4 | 96.6
| ASW | 0.0 | 12.3 | 87.7
| CHB | 0.0 | 5.8 | 94.2
| CHD | 0.9 | 7.3 | 91.7
| GIH | 1.0 | 5.9 | 93.1
| LWK | 0.0 | 7.3 | 92.7
| MEX | 0.0 | 3.4 | 96.6
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 2.0 | 98.0
| HapMapRevision=28
}}[[rs2229616]], a variant in the [[MC4R]] gene known as V103I, has been associated with appetite regulation, body mass index (and thus [[obesity]]), and other features of metabolic syndrome.{{PMID|18239646}}

The most common allele is [[rs2229616]](G); the rarer (A) allele encodes the 103I (isoleucine), and this (A) allele has been associated in a study of 8,000+ Caucasians with a significantly decreased waist circumference (-1.46 cm, p = 0.020), decreased glycosylated hemoglobin (HbA1c) (-0.09%, p = 0.040), and increased HDL-cholesterol (HDL-C) (+1.76 mg/dl, P = 0.056), but no change in blood pressure. The odds of having three or more components of the metabolic syndrome were substantially reduced among carriers of an [[rs2229616]](A) allele (odds ratio = 0.46, p = 0.003). Basically, [[rs2229616]](A) carriers are on average slightly leaner than [[rs2229616]](G;G) homozygotes.{{PMID|18239646}} 

{{PharmGKB
|RSID=rs2229616
|Name_s=MC4R: V103I
|Gene_s=MC4R
|Feature=
|Evidence=PubMed ID:15805150; PubMed ID:16278267; PubMed ID:17356525
|Annotation=A study in 1173 consecutive patients undergoing cardiac catheterization found that heterozygous carriers of the MC4R 103I allele had significantly lower triglyceride levels than individuals homozygous for the wild-type allele. Other studies report that the MC4R V103I polymorphism was associated with body weight regulation.
|Drugs=
|Drug Classes=
|Diseases=Cardiovascular Diseases; Obesity
|Curation Level=Curated
|PharmGKB Accession ID=PA162355900
}}

{{PMID|14973783|OA=1
}} Melanocortin-4 receptor gene variant I103 is negatively associated with obesity.

{{PMID|17357083|OA=1
}} Medical sequencing at the extremes of human body mass.

{{PMID|17519222}} Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene.

{{PMID|18377640|OA=1
}} Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia.

{{PMID|18454148|OA=1
}} Common variants near MC4R are associated with fat mass, weight and risk of obesity.

{{PMID|20092643|OA=1
}} Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS).

{{PMID|20127379|OA=1
}} From monogenic to polygenic obesity: recent advances.

{{PMID|20530052}} Melanocortin-4 receptor polymorphisms in Turkish pediatric obese patients.

{{PMID|22020349}} Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity- and metabolic-related traits in schizophrenic patients.

{{PMID|22310352}} Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene.

{{GET Evidence
|gene=MC4R
|aa_change=Val103Ile
|aa_change_short=V103I
|impact=protective
|qualified_impact=Low clinical importance, Uncertain protective
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs2229616
|overall_frequency_n=174
|overall_frequency_d=10758
|overall_frequency=0.016174
|n_genomes=2
|n_genomes_annotated=0
|n_haplomes=2
|n_articles=1
|n_articles_annotated=1
|qualityscore_case_control=1
|qualitycomment_case_control=Y
|gene_in_genetests=Y
|in_pharmgkb=Y
|pph2_score=0.014
|genetests_testable=Y
|nblosum100=-4
|autoscore=3
|webscore=N
|n_web_uneval=10
|variant_evidence=0
|clinical_importance=0
|summary_short=This variant was associated with a reduced incidence of obesity in a large meta-analysis of more than 55,000 individuals. 
}}

{{PMID Auto
|PMID=22989167
|Title=Association of melanocortin-4 receptor gene polymorphisms with obesity-related parameters in Malaysian Malays.
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | Illumina Human 1M}}