RACGAP1 gene

Variants (also called mutations) in the RACGAP1 gene have been identified in people with congenital dyserythropoietic anemia (CDA) type III. This condition is characterized by a shortage of red blood cells that is caused by abnormal red blood cell formation (dyserythropoietic anemia). In people with CDA type III, immature red blood cells cannot develop into functional, mature cells. As a result, the number of mature and functioning red blood cells decreases, which leads to weakness, an enlarged liver and spleen (hepatosplenomegaly), and the buildup of too much iron (iron overload) in people with CDA type III.

Most RACGAP1 gene variants change single protein building blocks (amino acids) in the protein. The RACGAP1 gene variants that cause CDA type III likely reduce the function of the protein and its ability to interact with many other proteins. A shortage of functional Rac GTPase-activating protein 1 impairs cytokinesis and the normal development of red blood cells. In people with CDA type III, immature red blood cells called erythroblasts are large and have more than one nucleus. These abnormal erythroblasts cannot develop into functional, mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia and the other features of CDA type III.