ALDH6A1: Aldehyde Dehydrogenase 6 Family Member A1
Mitochondrial methylmalonate semialdehyde dehydrogenase involved in valine and pyrimidine catabolism
Gene Information Card
| Symbol | ALDH6A1 |
|---|---|
| Full Name | Aldehyde Dehydrogenase 6 Family Member A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 4329 ncbi.nlm.nih.gov/gene/4329 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q02252 |
| OMIM ID | 603178 |
| HGNC ID | 408 |
| Aliases | MMSDH, MMSADHA, ALDH6 |
Description
ALDH6A1 encodes the mitochondrial enzyme methylmalonate semialdehyde dehydrogenase (MMSDH), which catalyzes the irreversible oxidative decarboxylation of malonate and methylmalonate semialdehydes to acetyl-CoA and propionyl-CoA, respectively. This enzyme is critical in the catabolism of valine and thymine. Mutations in ALDH6A1 cause methylmalonate semialdehyde dehydrogenase deficiency (MMSDHD), a rare autosomal recessive metabolic disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Methylmalonate semialdehyde dehydrogenase deficiency (MMSDHD) | Loss-of-function mutations impair conversion of methylmalonate semialdehyde to propionyl-CoA, leading to accumulation of toxic metabolites | ClinVar, OMIM #603178 |
| Developmental delay and metabolic acidosis | Deficient enzyme activity disrupts valine catabolism, causing organic acidemia | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.5 | High |
| Kidney | 12.3 | Medium |
| Heart | 8.7 | Medium |
| Brain | 5.2 | Low |
| Skeletal Muscle | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Hepatocyte model |
| HEK293 | 7.8 | Embryonic kidney |
| K562 | 3.2 | Leukemia line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358*) | Nonsense | <0.01% | Loss of function |
| c.154G>A (p.Gly52Arg) | Missense | <0.01% | Loss of function |
| c.889C>T (p.Arg297Trp) | Missense | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported ALDH6A1 mutations are loss-of-function, leading to MMSDHD.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003994 - methylmalonate-semialdehyde dehydrogenase (acylating) activity | • GO:0005739 - mitochondrion |
| • GO:0006573 - valine catabolic process | • GO:0055114 - oxidation-reduction process |
| • GO:0016620 - oxidoreductase activity | • acting on the aldehyde or oxo group of donors |
Pathways
• Valine
• leucine and isoleucine degradation (KEGG: hsa00280)
• Propanoate metabolism (KEGG: hsa00640)
• Beta-alanine metabolism (KEGG: hsa00410)
Protein Summary
The ALDH6A1 protein is a homotetrameric mitochondrial aldehyde dehydrogenase that uses NAD+ as cofactor. It catalyzes the conversion of methylmalonate semialdehyde to propionyl-CoA and malonate semialdehyde to acetyl-CoA. The enzyme is essential for the catabolism of valine and thymine. Deficiency leads to accumulation of 3-hydroxyisobutyrate and other metabolites.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALDH6A1 Knockout HEK293 Cell Line | EDJ-KQ5224 | Human | 4329 | Details Get a Quote |
| ALDH6A1 Knockout A-549 Cell Line | EDJ-KQ28243 | Human | 4329 | Details Get a Quote |
| ALDH6A1 Knockout HCT 116 Cell Line | EDJ-KQ28244 | Human | 4329 | Details Get a Quote |
| ALDH6A1 Knockout HeLa Cell Line | EDJ-KQ28245 | Human | 4329 | Details Get a Quote |
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