ALDH3A1
protein-codingaldehyde dehydrogenase 3 family member A1, the group of Aldehyde dehydrogenases
Gene summary
Aldehyde dehydrogenases oxidize various aldehydes to the corresponding acids. They are involved in the detoxification of alcohol-derived acetaldehyde and in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. The enzyme encoded by this gene forms a cytoplasmic homodimer that preferentially oxidizes aromatic and medium-chain (6 carbons or more) saturated and unsaturated aldehyde substrates. It is thought to promote resistance to UV and 4-hydroxy-2-nonenal-induced oxidative damage in the cornea. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2008]
- ALDH3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ALDH3A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000691.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 4 | 5 | |||
| missense | 1 | 39 | 3 | 1 | 44 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 40 | 4 | 5 | 50 |
Highest pathogenic variant AF is 0.000033461685
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000682.3 | 10 | MANE Select | |
| Ensembl | ENSP00000225740.6 | 10 | MANE Select | |
| RefSeq | NP_001128639.1 | 10 | Standard | |
| RefSeq | NP_001128640.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- beta-Alanine metabolism - Homo sapiens (human)
- Phenylalanine metabolism - Homo sapiens (human)
- Histidine metabolism - Homo sapiens (human)
- Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Biological Process
- cellular aldehyde metabolic process
- xenobiotic metabolic process
- oxidation-reduction process
Molecular Function
- 3-chloroallyl aldehyde dehydrogenase activity
- aldehyde dehydrogenase (NAD) activity
- aldehyde dehydrogenase [NAD(P)+] activity
- protein binding
- alcohol dehydrogenase (NADP+) activity
Cellular Component
- extracellular space
- endoplasmic reticulum
- cytosol
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000457500
- Coding exons
- 10
- Length
- 10960
- Individuals with no LoFs
- 125474
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 273
- Defined
- 125748
- p
- 0.00109
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.295 | 273 | 287 | 0.951 | 0.0000175 | 2940 |
| Missense (PolyPhen) | 85 | 102.07 | 0.83277 | 1135 | ||
| Synonymous | -0.583 | 137 | 129 | 1.07 | 0.00000900 | 884 |
| Loss of Function | -0.397 | 24 | 22.0 | 1.09 | 0.00000102 | 249 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.0028 | 0.0028 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.0011 | 0.0010 | notable |
| South Asian | 0.00075 | 0.00075 | rare |
| Other | 0.0026 | 0.0026 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde (Probable). They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation (Probable). Oxidizes medium and long chain aldehydes into non-toxic fatty acids (PubMed:1737758). Preferentially oxidizes aromatic aldehyde substrates (PubMed:1737758). Comprises about 50 percent of corneal epithelial soluble proteins (By similarity). May play a role in preventing corneal damage caused by ultraviolet light (By similarity). {ECO:0000250|UniProtKB:P47739, ECO:0000269|PubMed:1737758, ECO:0000305}.;
Intolerance Scores
- LoFtool
- 0.313
- RVIS EVS
- 0.11
- RVIS percentile EVS
- 62.14
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.249
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |