ALAS2 cDNA Clone – Aminolevulinate, Delta-, Synthase 2 (Human)

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]

ALAS2: Defects in ALAS2 are a cause of anemia sideroblastic X- linked (XLSA). 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. XLSA shows a variable hematologic response to pharmacologic doses of pyridoxine. Defects in ALAS2 are the cause of erythropoietic protoporphyria X-linked dominant (XLDPT). 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 a form of porphyria 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. 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). Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Transferase; Cofactor and Vitamin Metabolism - porphyrin and chlorophyll; Amino Acid Metabolism - glycine, serine and threonine; Mitochondrial; EC 2.3.1.37

Chromosomal Location of Human Ortholog: Xp11.21

Cellular Component: mitochondrial inner membrane; mitochondrial matrix; mitochondrion

Molecular Function: 5-aminolevulinate synthase activity; coenzyme binding; glycine binding; protein binding

Biological Process: cellular iron ion homeostasis; erythrocyte differentiation; heme biosynthetic process; hemoglobin biosynthetic process; response to hypoxia

Disease: Anemia, Sideroblastic, X-linked; Protoporphyria, Erythropoietic, X-linked