ALDH4A1 Gene: Aldehyde Dehydrogenase 4 Family Member A1
A key enzyme in proline and glutamate metabolism, linked to hyperprolinemia type II and potential roles in cancer and neurological disorders.
Gene Information Card
| Symbol | ALDH4A1 |
|---|---|
| Full Name | Aldehyde Dehydrogenase 4 Family Member A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 8659 ncbi.nlm.nih.gov/gene/8659 |
| Ensembl ID | ENSG00000159423 |
| UniProt ID | P30038 |
| OMIM ID | 606811 |
| HGNC ID | 406 |
| Aliases | P5CDH, ALDH4, P5CD, P5CDhL |
Description
The ALDH4A1 gene encodes a mitochondrial NAD+-dependent aldehyde dehydrogenase that catalyzes the second step of proline degradation, converting pyrroline-5-carboxylate (P5C) to glutamate. This enzyme is essential for proline and glutamate homeostasis, and its deficiency leads to hyperprolinemia type II. ALDH4A1 is also implicated in cellular redox balance and has been studied in the context of cancer metabolism and neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperprolinemia type II | Loss-of-function mutations in ALDH4A1 impair P5C dehydrogenase activity, leading to accumulation of P5C and proline in plasma and urine, causing seizures and intellectual disability. | OMIM #239510; ClinVar |
| Schizophrenia | Genetic variants in ALDH4A1 have been associated with altered glutamate metabolism, potentially contributing to schizophrenia pathophysiology. | NCBI Gene; PubMed studies |
| Cancer (various) | Dysregulation of ALDH4A1 expression in tumors may influence proline-dependent metabolic reprogramming and redox balance, affecting tumor growth and metastasis. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Heart | 6.1 | Medium |
| Brain | 4.2 | Low |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 9.7 | Embryonic kidney cell line |
| SH-SY5Y | 5.4 | Neuroblastoma cell line |
| A549 | 4.1 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1274G>A (p.Arg425Gln) | Missense | <0.01% | Reduced enzyme activity; associated with hyperprolinemia type II |
| c.154G>A (p.Gly52Arg) | Missense | <0.01% | Loss of function; reported in hyperprolinemia type II |
| c.1003C>T (p.Arg335*) | Nonsense | <0.01% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most ALDH4A1 mutations are loss-of-function, leading to hyperprolinemia type II due to impaired P5C dehydrogenase activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ALDH4A1.
Dominant Negative (DN)
No dominant-negative effects have been described for ALDH4A1 mutations.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003842 - 1-pyrroline-5-carboxylate dehydrogenase activity | • GO:0016620 - oxidoreductase activity |
| • acting on the aldehyde or oxo group of donors | • NAD or NADP as acceptor |
| • GO:0005739 - mitochondrion | • GO:0006561 - proline catabolic process |
| • GO:0006536 - glutamate metabolic process | • GO:0055114 - oxidation-reduction process |
Pathways
• Proline metabolism (Reactome: R-HSA-70618)
• Glutamate and glutamine metabolism (Reactome: R-HSA-8964539)
• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)
Protein Summary
ALDH4A1 encodes a 563-amino acid mitochondrial protein that functions as a homodimer. It catalyzes the NAD+-dependent oxidation of pyrroline-5-carboxylate (P5C) to glutamate, a key step in proline degradation. The enzyme is highly expressed in liver and kidney, and its deficiency results in hyperprolinemia type II. The protein contains a mitochondrial targeting sequence and an aldehyde dehydrogenase domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALDH4A1 Knockout HEK293 Cell Line | EDJ-KQ6319 | Human | 8659 | Details Get a Quote |
| ALDH4A1 Knockout A-549 Cell Line | EDJ-KQ30244 | Human | 8659 | Details Get a Quote |
| ALDH4A1 Knockout HCT 116 Cell Line | EDJ-KQ30245 | Human | 8659 | Details Get a Quote |
| ALDH4A1 Knockout HeLa Cell Line | EDJ-KQ30246 | Human | 8659 | Details Get a Quote |
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