We found that many KRAB-ZNF gene clusters targeted by natural selection have been connected with multiple medical conditions of relevance for human health, for instance, muscle weakness, obesity, hyperparathyroidism, degenerative polyarthritis, heart diseases, azoospermia, cognitive disabilities, and multiple types of cancers, among others. This evidence concerns the gene ZNF44 and obesity due to melanocortin 4 receptor deficiency.