ALAS2

The product of this gene specifies an erythroid-specific mitochondrially located enzyme. The encoded protein catalyzes the first step in the heme biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive sideroblastic anemia. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Full Name

5'-Aminolevulinate Synthase 2

Biological Process

Cellular iron ion homeostasis Source: UniProtKB
Erythrocyte development Source: GO_Central
Erythrocyte differentiation Source: UniProtKB
Heme biosynthetic process Source: UniProtKB
Hemoglobin biosynthetic process Source: UniProtKB
Oxygen homeostasis Source: UniProtKB
Protoporphyrinogen IX biosynthetic process Source: UniProtKB-UniPathway
Response to hypoxia Source: UniProtKB

Cellular Location

Mitochondrion matrix

Involvement in disease

Anemia, sideroblastic, 1 (SIDBA1): A form of sideroblastic anemia that shows a variable hematologic response to pharmacologic doses of pyridoxine. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus.
Erythropoietic protoporphyria, X-linked dominant (XLDPT): The disease is caused by variants affecting the gene represented in this entry. Gain of function mutations in ALS2 are responsible for XLDPT, but they can also be a possible aggravating factor in congenital erythropoietic porphyria and other erythropoietic disorders caused by mutations in other genes (PubMed:21309041). A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. XLDPT is characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.