GATA6R456G/R456G cell also reduced expression of GATA4. While these data illustrate multiple mechanisms for depleting PDX1 expression and account for the prominent association of CHD and pancreatic agenesis in patients with GATA6 LoF and exon four missense variants, the pathways leading to this shared consequence were strikingly different. The gene discussed is PDX1; the disease is pancreatic agenesis.