ALDH1A1
protein-codingaldehyde dehydrogenase 1 family member A1, the group of Aldehyde dehydrogenases
Gene summary
The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet. [provided by RefSeq, Mar 2011]
- PUMB1
- ALDH1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~179.8 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 ALDH1A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000689.5. 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 | 2 | 2 | 4 | |||
| missense | 36 | 1 | 1 | 38 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 42 | 3 | 1 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000680.2 | 13 | MANE Select | |
| Ensembl | ENSP00000297785.3 | 13 | MANE Select | |
| Ensembl | ENSP00000366138.1 | 8 | Standard | |
| Ensembl | ENSP00000366138.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Retinol metabolism - Homo sapiens (human)
- Cyclophosphamide Pathway, Pharmacodynamics
- Ifosfamide Pathway, Pharmacokinetics
- Ifosfamide Pathway, Pharmacodynamics
- Cyclophosphamide Action Pathway
Biological Process
- retinoid metabolic process
- ethanol oxidation
- cellular aldehyde metabolic process
- retinol metabolic process
- positive regulation of GTPase activity
Molecular Function
- retinal dehydrogenase activity
- aldehyde dehydrogenase (NAD) activity
- GTPase activator activity
- androgen binding
- benzaldehyde dehydrogenase (NAD+) activity
Cellular Component
- cytoplasm
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297785
- Coding exons
- 13
- Length
- 179781
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125739
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 199 | 276 | 0.720 | 0.0000142 | 3260 |
| Missense (PolyPhen) | 57 | 116.85 | 0.4878 | 1421 | ||
| Synonymous | -0.340 | 106 | 102 | 1.04 | 0.00000561 | 969 |
| Loss of Function | 4.13 | 4 | 27.3 | 0.146 | 0.00000130 | 347 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Can convert/oxidize retinaldehyde to retinoic acid. Binds free retinal and cellular retinol-binding protein-bound retinal (By similarity). May have a broader specificity and oxidize other aldehydes in vivo (PubMed:19296407, PubMed:26373694, PubMed:25450233). {ECO:0000250|UniProtKB:P51647, ECO:0000269|PubMed:19296407, ECO:0000269|PubMed:25450233, ECO:0000269|PubMed:26373694}.;
Recessive Scores
- pRec
- 0.386
Intolerance Scores
- LoFtool
- 0.271
- RVIS EVS
- -0.54
- RVIS percentile EVS
- 20.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.880
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |