Causes of Sickle Cell Disease

Sickle cell disease comprises a group of rare genetic disorders in which red blood cells adopt a sickle-like shape and die prematurely, resulting in fewer red blood cells available to carry oxygen throughout the body.

These misshapen red blood cells are stiffer and tend to stick to other cells, making them more prone to become stuck and obstruct small blood vessels. This in turn may restrict blood flow to different tissues and organs, causing damage and leading to painful episodes known as pain crises.


Sickle cell disease is caused by mutations in the beta-globin (HBB) gene that lead to the production of an abnormal version of a subunit of hemoglobin — the protein responsible for carrying oxygen in red blood cells. This mutated version of the protein is known as hemoglobin S. Other hemoglobin variants include A (the most common type found in healthy adults), A2, C, D, E, and F.

Hemoglobin S results from a change in a single amino acid, or protein building block. This causes mutated proteins to more easily clump together inside red blood cells, forming long, stiff fibers. These fibers make red blood cells more fragile and contort them into the sickle-like shape characteristic of the disorder.

In addition to hemoglobin S, mutations in HBB may also result in the production of other defective versions of hemoglobin, such as hemoglobin C and E.


Sickle cell disease is considered an autosomal recessive disorder, meaning that a person must receive two defective gene copies — one from each parent — to develop the condition. The disease cannot be transmitted from person to person and is not caused by anything that parents might have done before or during pregnancy.

In people with sickle cell disease, at least one of the inherited HBB gene copies contains instructions for making hemoglobin S. When both copies of the gene encode hemoglobin S, a person is said to have sickle cell anemia, the most common and often the most severe form of sickle cell disease.

Other types of sickle cell disease arise from having a mutated HBB copy encoding hemoglobin S and a different mutation resulting in the production of another faulty version of hemoglobin, such as hemoglobin C.

People with a single copy of the S variant and one copy of the healthy hemoglobin A variant have what is known as the sickle cell trait. These individuals usually do not show any symptoms of sickle cell, but can still pass the S variant on to their biological children.

Affected populations

Sickle cell disease can affect people of any ethnic background. It is more common, however, in individuals of African, Mediterranean, Middle Eastern, and Indian ancestry.


Last updated: July 20, 2021


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