ALAS2

ALAS2 (Delta-Aminolevulinic Acid Synthase 2) is a gene that encodes a protein involved in the first step of the heme biosynthesis pathway. This gene is specifically expressed in the erythroid cells of the bone marrow, which are responsible for the production of red blood cells. Mutations in this gene can lead to a group of disorders known as porphyrias, specifically X-linked sideroblastic anemia and X-linked protoporphyria.

Function

The ALAS2 gene provides instructions for making an enzyme called delta-aminolevulinic acid synthase 2. This enzyme is found in developing red blood cells, where it initiates the production of heme. Heme is a vital molecule that has several functions, including forming part of hemoglobin, the protein in red blood cells that carries oxygen.

Clinical significance

Mutations in the ALAS2 gene can cause X-linked sideroblastic anemia and X-linked protoporphyria. These conditions are characterized by a shortage of red blood cells (anemia), which can cause fatigue, weakness, and pale skin. In X-linked protoporphyria, affected individuals can also experience painful skin sensitivity to sunlight.

Genetics

The ALAS2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. However, because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females.

See also

• Heme synthesis
• X-linked recessive inheritance
• Erythropoiesis
• Porphyria