Consistent with this hypothesis, the corresponding de novo degron variants of AFF4 that are associated with CHOPS (Cognitive impairment and Coarse facies, Heart defects, Obesity, Pulmonary involvement, Short stature, and Skeletal dysplasia) syndrome (OMIM#616368) were shown to be more resistant to degradation upon co-transfection with the SIAH1 ubiquitin ligase [20, 21]. Here, AFF4 is linked to obesity due to melanocortin 4 receptor deficiency.