To investigate the potential contribution of genetic variation in GPR10 to severe human obesity, we interrogated exome sequencing and targeted resequencing data on 2548 European ancestry individuals with severe, early-onset obesity recruited to the Genetics of Obesity study (GOOS; www.goos.org.uk) (mean Body Mass Index (BMI) standard deviation score>3; age of onset <10 years); mutations in known obesity genes had been excluded. The gene discussed is PRLHR; the disease is obesity due to melanocortin 4 receptor deficiency.