Paediatric disorders - additional genes

Gene: MC4R

Amber List (moderate evidence)

MC4R (melanocortin 4 receptor)
EnsemblGeneIds (GRCh38): ENSG00000166603
EnsemblGeneIds (GRCh37): ENSG00000166603
OMIM: 155541, Gene2Phenotype
MC4R is in 2 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: This gene should be promote to Green at the next GMS panel update. There is sufficient evidence to support this gene-disease association (variants in the MC4R gene are the most common cause of monogenic obesity, >3 cases). As highlighted in the review by Ian Berry, the R27 panel represents an alternative test to R149 that may be requested for these patients which warrants inclusion of the MC4R gene on this panel.
Created: 30 Jul 2025, 10:41 a.m. | Last Modified: 30 Jul 2025, 10:41 a.m.
Panel Version: 7.3

Ian Berry (Leeds Genetics Laboratory)

Green List (high evidence)

Well-established OMIM association. Gene on R149 Severe Early Onset Obesity panel (green). Many R27 referrals include ID & obesity/overgrowth so may be a partial explanation for many patients referred. This is the primary/most common R149 gene that it not currently on the R27 panel and inclusion would minimise management of re-analysis requests for R149 for patient who meet both the R27 and potentially R149 eligibility criteria.
Sources: Expert Review
Created: 2 Jun 2025, 12:44 p.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Obesity (BMIQ20), OMIM:618406
  • {Obesity, resistence to (BMIQ20)}, OMIM:618306
Tags
Q3_25_promote_green Q3_25_NHS_review
OMIM
155541
Clinvar variants
Variants in MC4R
Penetrance
Incomplete
Panels with this gene

History Filter Activity

30 Jul 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: mc4r has been classified as Amber List (Moderate Evidence).

30 Jul 2025, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: MC4R were changed from to Obesity (BMIQ20), OMIM:618406; {Obesity, resistence to (BMIQ20)}, OMIM:618306

30 Jul 2025, Gel status: 0

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_promote_green tag was added to gene: MC4R. Tag Q3_25_NHS_review tag was added to gene: MC4R.

2 Jun 2025, Gel status: 0

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

Ian Berry (Leeds Genetics Laboratory)

gene: MC4R was added gene: MC4R was added to Paediatric disorders - additional genes. Sources: Expert Review Mode of inheritance for gene: MC4R was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Penetrance for gene: MC4R were set to Incomplete Review for gene: MC4R was set to GREEN