ALAS2 Gene
5'-Aminolevulinate Synthase 2: Key Enzyme in Heme Biosynthesis
Gene Information Card
| Symbol | ALAS2 |
|---|---|
| Full Name | 5'-aminolevulinate synthase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | Xp11.21 |
| NCBI Gene ID | 212 ncbi.nlm.nih.gov/gene/212 |
| Ensembl ID | ENSG00000158578 |
| UniProt ID | P22557 |
| OMIM ID | 301300 |
| HGNC ID | 398 |
| Aliases | ALAS-E, ASB, XLSA, ANH1 |
Description
ALAS2 (5'-aminolevulinate synthase 2) encodes the erythroid-specific isoform of 5-aminolevulinate synthase, the first and rate-limiting enzyme in the heme biosynthesis pathway. This mitochondrial enzyme catalyzes the condensation of glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA). Mutations in ALAS2 are associated with X-linked sideroblastic anemia (XLSA) and, rarely, X-linked protoporphyria (XLP).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked sideroblastic anemia (XLSA) | Loss-of-function mutations reduce ALAS2 enzymatic activity, impairing heme synthesis and causing mitochondrial iron accumulation in erythroblasts. | ClinVar, OMIM |
| X-linked protoporphyria (XLP) | Gain-of-function mutations increase ALAS2 activity, leading to accumulation of protoporphyrin IX and photosensitivity. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | High |
| Spleen | 3.2 | Medium |
| Liver | 1.1 | Low |
| Whole blood | 0.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (erythroleukemia) | 15.3 | Erythroid lineage |
| HEL (erythroleukemia) | 14.1 | Erythroid lineage |
| TF-1 (erythroleukemia) | 11.7 | Erythroid lineage |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1642C>T (p.Arg548Cys) | Missense | Common in XLSA | Reduced catalytic activity |
| c.1735A>G (p.Asn579Ser) | Missense | Rare | Gain-of-function, associated with XLP |
| c.1215+1G>A | Splice site | Rare | Loss-of-function, XLSA |
Mutation functional classification
Loss of Function (LOF)
Most XLSA-associated mutations (e.g., p.Arg548Cys) reduce ALAS2 enzymatic activity, impairing heme synthesis and causing microcytic hypochromic anemia with ring sideroblasts.
Gain of Function (GOF)
Mutations such as p.Asn579Ser increase ALAS2 activity, leading to protoporphyrin IX accumulation and X-linked protoporphyria.
Dominant Negative (DN)
Not reported for ALAS2.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003870 - 5-aminolevulinate synthase activity | • GO:0006783 - heme biosynthetic process |
| • GO:0005739 - mitochondrion | • GO:0006782 - protoporphyrinogen IX biosynthetic process |
| • GO:0048821 - erythrocyte development |
Pathways
• Heme biosynthesis (Reactome: R-HSA-189451)
• Porphyrin metabolism (KEGG: hsa00860)
Protein Summary
ALAS2 is a 587-amino acid mitochondrial enzyme (UniProt P22557) that catalyzes the first step of heme biosynthesis in erythroid cells. It requires pyridoxal phosphate (PLP) as a cofactor. The protein is synthesized as a precursor with a mitochondrial targeting sequence and is processed to its mature form upon import. Mutations affecting PLP binding or catalytic residues lead to X-linked sideroblastic anemia, while gain-of-function mutations cause X-linked protoporphyria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALAS2 Knockout HEK293 Cell Line | EDJ-KQ4030 | Human | 212 | Details Get a Quote |
| ALAS2 Knockout HeLa Cell Line | EDJ-KQ52589 | Human | 212 | Details Get a Quote |
| ALAS2 Knockout A-549 Cell Line | EDJ-KQ61067 | Human | 212 | Details Get a Quote |
| ALAS2 Knockout HCT 116 Cell Line | EDJ-KQ69550 | Human | 212 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
