phenotypic heterogeneity phenotypic heterogeneity phenotypic heterogeneity describes different mutations in the same gene that can sometimes give rise to strikingly different phenotypes. e.g., certain loss-of-function mutations in the ret gene, which encodes a receptor tyrosine kinase, can cause dominantly inherited failure of development of colonic ganglia, leading to defective colonic motility and severe chronic constipation (hirschsprung disease).