Recently, using functional clustering analysis of genes with rare variants, we have shown that in people with extreme obesity (BMI 45–65 kg/m2), the protocadherin (PCDH) genes on chromosome 5q31 harbor a surplus of rare variation with a moderate-to-high predicted biological effect (Mariman et al. 2014). This evidence concerns the gene PCDH11X and obesity due to melanocortin 4 receptor deficiency.