Severe early-onset obesity

Gene: MC3R

Red List (low evidence)

MC3R (melanocortin 3 receptor)
EnsemblGeneIds (GRCh38): ENSG00000124089
EnsemblGeneIds (GRCh37): ENSG00000124089
OMIM: 155540, Gene2Phenotype
MC3R is in 1 panel

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Red List (low evidence)

PMID:31090190 reported a systematic review and meta-analysis of genetic association studies in all ages and ethnicities, which demonstrated that rare heterozygous partial/complete LOF variants in the coding region of MC3R confer three-time increased risk of obesity in individuals. Hence, this is a susceptibility gene and the data does not suggest causation of severe early-onset obesity by MC3R variants as detailed in the eligibility criteria on the National Genomic Test Directory (https://www.england.nhs.uk/wp-content/uploads/2018/08/rare-inherited-disease-eligibility-criteria-v8.0.pdf)

This gene is also associated with susceptibility to obesity in OMIM (MIM #602025).

This gene should therefore be rated red on this panel.
Created: 16 Jun 2025, 6:14 p.m. | Last Modified: 16 Jun 2025, 6:14 p.m.
Panel Version: 5.7

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Obesity, severe, susceptibility to, BMIQ9}, OMIM:602025

Publications

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

PMID: 31090190 described a meta analysis of ~3k cases (including children) with obesity & ~2.5k controls and found a significant enrichment of LoF MC3R variants in obesity cases (OR = 3.07). Enough evidence for the green rating.
Sources: Literature
Created: 12 Jan 2025, 10:43 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
obesity

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
Phenotypes
  • {Obesity, severe, susceptibility to, BMIQ9}, OMIM:602025
OMIM
155540
Clinvar variants
Variants in MC3R
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

16 Jun 2025, Gel status: 1

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: mc3r has been classified as Red List (Low Evidence).

16 Jun 2025, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: MC3R were changed from obesity to {Obesity, severe, susceptibility to, BMIQ9}, OMIM:602025

16 Jun 2025, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: MC3R were set to PMID: 31090190

12 Jan 2025, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Dmitrijs Rots (Children's Clinical University Hospital)

gene: MC3R was added gene: MC3R was added to Severe early-onset obesity. Sources: Literature Mode of inheritance for gene: MC3R was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MC3R were set to PMID: 31090190 Phenotypes for gene: MC3R were set to obesity Penetrance for gene: MC3R were set to Incomplete Review for gene: MC3R was set to GREEN