ALAD Gene (Aminolevulinate Dehydratase)
Key enzyme in heme biosynthesis; mutations cause ALAD porphyria and lead poisoning susceptibility
Gene Information Card
| Symbol | ALAD |
|---|---|
| Full Name | Aminolevulinate Dehydratase |
| Gene Type | Protein coding |
| Chromosomal Location | 9q32 |
| NCBI Gene ID | 210 ncbi.nlm.nih.gov/gene/210 |
| Ensembl ID | ENSG00000148218 |
| UniProt ID | P13716 |
| OMIM ID | 125270 |
| HGNC ID | 395 |
| Aliases | ALADH, PBGS, porphobilinogen synthase |
Description
The ALAD gene encodes aminolevulinate dehydratase (also known as porphobilinogen synthase), the second enzyme in the heme biosynthesis pathway. It catalyzes the condensation of two molecules of 5-aminolevulinic acid to form porphobilinogen. Mutations in ALAD cause ALAD porphyria (ADP), a rare autosomal recessive disorder, and variants influence susceptibility to lead poisoning. The enzyme is inhibited by lead, contributing to lead-induced anemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| ALAD porphyria (ADP) | Loss-of-function mutations in ALAD reduce enzyme activity, leading to accumulation of 5-aminolevulinic acid and neurovisceral symptoms. | OMIM #612740; ClinVar |
| Lead poisoning susceptibility | Lead binds to ALAD, inhibiting its activity; genetic variants (e.g., rs1800435) alter enzyme sensitivity to lead. | NCBI Gene; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.2 | Medium |
| Bone marrow | 12.5 | Medium |
| Kidney | 9.8 | Low |
| Brain | 6.3 | Low |
| Heart | 4.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Hepatocyte line |
| K562 | 11.3 | Erythroleukemia line |
| HEK293 | 7.5 | Embryonic kidney line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.177C>T (p.Arg59Ter) | Nonsense | Rare | Loss of function; associated with ADP |
| c.823G>A (p.Gly275Arg) | Missense | Rare | Reduced enzyme activity; ADP |
| rs1800435 (p.Lys59Asn) | Missense | Common (allele freq ~10%) | Alters lead binding affinity |
Mutation functional classification
Loss of Function (LOF)
Most ALAD mutations (nonsense, missense, frameshift) reduce or abolish enzyme activity, causing ALAD porphyria.
Gain of Function (GOF)
Not reported for ALAD.
Dominant Negative (DN)
Not reported; ALAD porphyria is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004655 - porphobilinogen synthase activity | • GO:0006783 - heme biosynthetic process |
| • GO:0008270 - zinc ion binding | • GO:0005829 - cytosol |
Pathways
• Heme biosynthesis (Reactome: R-HSA-189451)
• Porphyrin metabolism (KEGG: hsa00860)
Protein Summary
Aminolevulinate dehydratase (ALAD) is a cytosolic homooctameric enzyme that requires zinc for activity. It catalyzes the asymmetric condensation of two 5-aminolevulinic acid molecules to form porphobilinogen, a key step in heme synthesis. The enzyme is highly expressed in liver and bone marrow. Lead inhibits ALAD by displacing zinc, leading to accumulation of 5-aminolevulinic acid and contributing to lead toxicity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALAD Knockout HEK293 Cell Line | EDJ-KQ3454 | Human | 210 | Details Get a Quote |
| NAALAD2 Knockout HEK293 Cell Line | EDJ-KQ6859 | Human | 10003 | Details Get a Quote |
| NAALADL1 Knockout HEK293 Cell Line | EDJ-KQ6862 | Human | 10004 | Details Get a Quote |
| NAALADL2 Knockout HEK293 Cell Line | EDJ-KQ11777 | Human | 254827 | Details Get a Quote |
| ALAD Knockout HCT 116 Cell Line | EDJ-KQ25196 | Human | 210 | Details Get a Quote |
| ALAD Knockout HeLa Cell Line | EDJ-KQ25197 | Human | 210 | Details Get a Quote |
| NAALADL2 Knockout HCT 116 Cell Line | EDJ-KQ40179 | Human | 254827 | Details Get a Quote |
| ALAD Knockout A-549 Cell Line | EDJ-KQ23814 | Human | 210 | Details Get a Quote |
| NAALAD2 Knockout HCT 116 Cell Line | EDJ-KQ31433 | Human | 10003 | Details Get a Quote |
| NAALAD2 Knockout HeLa Cell Line | EDJ-KQ55297 | Human | 10003 | Details Get a Quote |
| NAALADL1 Knockout HeLa Cell Line | EDJ-KQ55298 | Human | 10004 | Details Get a Quote |
| NAALADL2 Knockout HeLa Cell Line | EDJ-KQ59262 | Human | 254827 | Details Get a Quote |
| NAALAD2 Knockout A-549 Cell Line | EDJ-KQ63778 | Human | 10003 | Details Get a Quote |
| NAALADL1 Knockout A-549 Cell Line | EDJ-KQ63779 | Human | 10004 | Details Get a Quote |
| NAALADL2 Knockout A-549 Cell Line | EDJ-KQ67729 | Human | 254827 | Details Get a Quote |
Displaying Records 1 To 15 Of 16 Records
