ALAS1: 5'-Aminolevulinate Synthase 1
Key enzyme in heme biosynthesis; associated with X-linked sideroblastic anemia and porphyria
Gene Information Card
| Symbol | ALAS1 |
|---|---|
| Full Name | 5'-Aminolevulinate Synthase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.2 |
| NCBI Gene ID | 211 ncbi.nlm.nih.gov/gene/211 |
| Ensembl ID | ENSG00000123360 |
| UniProt ID | P13196 |
| OMIM ID | 125290 |
| HGNC ID | 397 |
| Aliases | ALAS, ALAS-H, ALAS1, MIG5 |
Description
ALAS1 encodes the mitochondrial enzyme 5-aminolevulinate synthase 1, which catalyzes the first and rate-limiting step of heme biosynthesis: the condensation of glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA). This gene is ubiquitously expressed and is regulated by heme via feedback inhibition. Mutations in ALAS1 are associated with X-linked sideroblastic anemia and certain porphyrias.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked sideroblastic anemia | Loss-of-function mutations reduce heme synthesis, leading to mitochondrial iron accumulation and ineffective erythropoiesis. | ClinVar, OMIM |
| X-linked protoporphyria | Gain-of-function mutations increase ALAS1 activity, causing accumulation of protoporphyrin IX and photosensitivity. | OMIM, ClinVar |
| Acute intermittent porphyria (secondary) | Dysregulation of ALAS1 expression can exacerbate heme pathway defects. | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Bone marrow | 8.3 | Medium |
| Heart | 6.1 | Medium |
| Brain | 4.2 | Low |
| Kidney | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocyte cell line |
| K562 | 9.7 | Erythroleukemia cell line |
| HEK293 | 5.4 | Embryonic kidney cell line |
| HeLa | 4.1 | Cervical cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1735C>T (p.Arg579Ter) | Nonsense | Rare | Loss of function; associated with X-linked sideroblastic anemia |
| c.1642G>A (p.Gly548Arg) | Missense | Rare | Gain of function; associated with X-linked protoporphyria |
| c.1216C>T (p.Arg406Trp) | Missense | Rare | Loss of function; reported in sideroblastic anemia |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce enzyme activity, leading to X-linked sideroblastic anemia.
Gain of Function (GOF)
Missense mutations that increase enzyme activity, causing X-linked protoporphyria.
Dominant Negative (DN)
Not reported for ALAS1.
View complete mutation data：
Gene Ontology (GO)
| • 5-aminolevulinate synthase activity (GO:0003870) | • heme biosynthetic process (GO:0006783) |
| • mitochondrion (GO:0005739) | • biosynthetic process (GO:0009058) |
| • identical protein binding (GO:0042802) |
Pathways
• Heme biosynthesis (KEGG: hsa00860)
• Porphyrin and chlorophyll metabolism (Reactome: R-HSA-189445)
Protein Summary
ALAS1 is a homodimeric mitochondrial enzyme (64 kDa per subunit) that requires pyridoxal phosphate as a cofactor. It catalyzes the condensation of glycine and succinyl-CoA to produce 5-aminolevulinic acid. The protein is synthesized in the cytoplasm and imported into mitochondria via an N-terminal targeting sequence. Heme negatively regulates ALAS1 at the transcriptional and post-translational levels.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALAS1 Knockout HEK293 Cell Line | EDJ-KQ3366 | Human | 211 | Details Get a Quote |
| ALAS1 Knockout A-549 Cell Line | EDJ-KQ26372 | Human | 211 | Details Get a Quote |
| ALAS1 Knockout HCT 116 Cell Line | EDJ-KQ26374 | Human | 211 | Details Get a Quote |
| ALAS1 Knockout HeLa Cell Line | EDJ-KQ26375 | Human | 211 | Details Get a Quote |
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