ALDH1A2 (ALDH Family 1 Member A2): Retinaldehyde Dehydrogenase 2, Key Enzyme in Retinoic Acid Synthesis
A comprehensive biomedical overview of ALDH1A2, its genomic context, expression, disease associations, and functional roles.
Gene Information Card
| Symbol | ALDH1A2 |
|---|---|
| Full Name | Aldehyde Dehydrogenase 1 Family Member A2 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.3 (GRCh38) |
| NCBI Gene ID | 8854 ncbi.nlm.nih.gov/gene/8854 |
| Ensembl ID | ENSG00000128918 |
| UniProt ID | O94788 |
| OMIM ID | 603687 |
| HGNC ID | 408 |
| Aliases | RALDH2, RALDH(II), RALDH-2, MCOPS8 |
Description
ALDH1A2 encodes retinaldehyde dehydrogenase 2 (RALDH2), a cytosolic enzyme that catalyzes the irreversible oxidation of retinaldehyde to retinoic acid (RA), the active metabolite of vitamin A. This enzyme is critical for embryonic development, particularly in the formation of the heart, limbs, and central nervous system, and also plays roles in adult tissue homeostasis and immune regulation. Mutations and altered expression are linked to various developmental disorders and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Microphthalmia, syndromic 8 (MCOPS8) | Biallelic loss-of-function mutations reduce RA synthesis, disrupting eye development. | OMIM (603687); PMID: 28575664 |
| Congenital heart defects | Reduced RA signaling due to ALDH1A2 variants impairs cardiac outflow tract development. | PMID: 28575664; PMID: 31585110 |
| Diaphragmatic hernia (congenital) | Loss of RA signaling affects diaphragm muscle formation. | PMID: 28575664 |
| Colorectal cancer | Altered ALDH1A2 expression affects RA levels, influencing cell differentiation and proliferation. | COSMIC; PMID: 26987663 |
| Prostate cancer | Downregulation of ALDH1A2 leads to reduced RA, promoting tumor progression. | PMID: 26987663 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 25.1 | High |
| Liver | 18.3 | High |
| Kidney | 12.4 | Medium |
| Testis | 8.7 | Medium |
| Lung | 5.2 | Low |
| Brain | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Hep G2 (liver) | 20.5 | High expression |
| A-549 (lung) | 6.3 | Moderate |
| MCF7 (breast) | 2.8 | Low |
| K-562 (leukemia) | 1.2 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1105C>T (p.Arg369Ter) | Nonsense | Rare (MAF <0.01) | Loss of function; associated with MCOPS8 |
| c.841G>A (p.Glu281Lys) | Missense | Rare | Impaired catalytic activity; reduced RA synthesis |
| c.1547A>G (p.Tyr516Cys) | Missense | Rare | Potential dominant-negative effect; reduced enzyme activity |
| c.1234delC (p.Leu412TrpfsTer5) | Frameshift | Rare | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations are loss-of-function, leading to reduced or absent RALDH2 activity, causing retinoic acid deficiency and developmental defects.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression in some cancers may increase RA catabolism, but not due to mutations.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming inactive dimers, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • aldehyde dehydrogenase (NAD+) activity | • retinal dehydrogenase activity |
| • oxidoreductase activity | • retinoic acid biosynthetic process |
| • embryonic limb morphogenesis | • heart development |
| • response to retinoic acid |
Pathways
• Retinol metabolism
• Retinoic acid biosynthesis
• Vitamin A metabolism
• Signaling by Retinoic Acid (Reactome)
Protein Summary
ALDH1A2 encodes a 518-amino acid protein (UniProt O94788) that forms homodimers and requires NAD+ as a cofactor. The enzyme converts all-trans-retinal to all-trans-retinoic acid, a key morphogen. It is localized in the cytoplasm and is highly expressed in embryonic tissues and adult organs such as the small intestine and liver. Post-translational modifications include phosphorylation, which may regulate activity. The protein has a conserved aldehyde dehydrogenase domain and is essential for RA-dependent gene regulation via nuclear receptors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALDH1A2 Knockout HEK293 Cell Line | EDJ-KQ6383 | Human | 8854 | Details Get a Quote |
| ALDH1A2 Knockout HeLa Cell Line | EDJ-KQ30393 | Human | 8854 | Details Get a Quote |
| ALDH1A2 Knockout A-549 Cell Line | EDJ-KQ63506 | Human | 8854 | Details Get a Quote |
| ALDH1A2 Knockout HCT 116 Cell Line | EDJ-KQ71973 | Human | 8854 | Details Get a Quote |
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