ALDH18A1
Aldehyde Dehydrogenase 18 Family Member A1
Gene Information Card
| Symbol | ALDH18A1 |
|---|---|
| Full Name | Aldehyde Dehydrogenase 18 Family Member A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.1 |
| NCBI Gene ID | 5832 ncbi.nlm.nih.gov/gene/5832 |
| Ensembl ID | ENSG00000059573 |
| UniProt ID | P54886 |
| OMIM ID | 138250 |
| HGNC ID | 9722 |
| Aliases | P5CS, GSAS, PYCS, SPG9A, SPG9B, ADCL2, ARCL3A |
Description
ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthase (P5CS), a bifunctional enzyme with glutamate 5-kinase and gamma-glutamyl phosphate reductase activities. It catalyzes the first two steps of proline and ornithine biosynthesis from glutamate, playing a critical role in amino acid metabolism, redox balance, and collagen synthesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cutis laxa, autosomal recessive, type IIIA (ARCL3A) | Loss-of-function mutations reduce proline and ornithine synthesis, impairing connective tissue integrity. | ClinVar, OMIM |
| Spastic paraplegia 9A, autosomal dominant (SPG9A) | Dominant-negative or gain-of-function mutations disrupt enzyme regulation, leading to neurodegeneration. | OMIM, PubMed |
| Spastic paraplegia 9B, autosomal recessive (SPG9B) | Biallelic loss-of-function variants cause early-onset spasticity and developmental delay. | OMIM, ClinVar |
| Cutis laxa, autosomal dominant, type II (ADCL2) | Heterozygous missense mutations with dominant-negative effect on P5CS activity. | OMIM, HGNC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 15.2 | Medium |
| Kidney | 12.8 | Medium |
| Liver | 11.5 | Medium |
| Pancreas | 9.7 | Low |
| Brain | 8.3 | Low |
| Heart | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | High expression |
| HepG2 | 14.1 | Medium expression |
| K-562 | 6.2 | Low expression |
| SH-SY5Y | 5.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1274G>A (p.Arg425Gln) | Missense | Unknown | Dominant-negative; associated with SPG9A |
| c.1228C>T (p.Arg410Trp) | Missense | Unknown | Loss-of-function; ARCL3A |
| c.746G>A (p.Arg249His) | Missense | Unknown | Loss-of-function; ARCL3A |
| c.1270C>T (p.Arg424Trp) | Missense | Unknown | Dominant-negative; ADCL2 |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense or nonsense variants reducing P5CS enzymatic activity, leading to cutis laxa and spastic paraplegia 9B.
Gain of Function (GOF)
Not well documented; some dominant mutations may increase activity but evidence is limited.
Dominant Negative (DN)
Heterozygous missense mutations (e.g., Arg425Gln) that interfere with wild-type P5CS function, causing SPG9A and ADCL2.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004349 – glutamate 5-kinase activity | • GO:0004350 – glutamate-5-semialdehyde dehydrogenase activity |
| • GO:0006561 – proline biosynthetic process | • GO:0006592 – ornithine biosynthetic process |
| • GO:0005737 – cytoplasm | • GO:0005829 – cytosol |
Pathways
• Proline biosynthesis (Reactome: R-HSA-70614)
• Arginine and proline metabolism (KEGG: hsa00330)
• Urea cycle and metabolism of amino groups (Reactome: R-HSA-70635)
Protein Summary
The P5CS protein (UniProt P54886) is a 795-amino acid bifunctional enzyme localized to the cytoplasm. It catalyzes the conversion of glutamate to glutamate-5-semialdehyde via ATP- and NADPH-dependent reactions. This intermediate is used for proline and ornithine synthesis. Mutations in ALDH18A1 disrupt these pathways, leading to connective tissue disorders and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALDH18A1 Knockout HEK293 Cell Line | EDJ-KQ2614 | Human | 5832 | Details Get a Quote |
| ALDH18A1 Knockout A-549 Cell Line | EDJ-KQ24726 | Human | 5832 | Details Get a Quote |
| ALDH18A1 Knockout HCT 116 Cell Line | EDJ-KQ24728 | Human | 5832 | Details Get a Quote |
| ALDH18A1 Knockout HeLa Cell Line | EDJ-KQ24729 | Human | 5832 | Details Get a Quote |
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