ALDH8A1
protein-codingaldehyde dehydrogenase 8 family member A1, the group of Aldehyde dehydrogenases
Gene summary
This gene encodes a member of the aldehyde dehydrogenase family of proteins. The encoded protein has been implicated in the synthesis of 9-cis-retinoic acid and in the breakdown of the amino acid tryptophan. This enzyme converts 9-cis-retinal into the retinoid X receptor ligand 9-cis-retinoic acid, and has approximately 40-fold higher activity with 9-cis-retinal than with all-trans-retinal. In addition, this enzyme has been shown to catalyze the conversion of 2-aminomuconic semialdehyde to 2-aminomuconate in the kynurenine pathway of tryptophan catabolism. [provided by RefSeq, Jul 2018]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.7 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 ALDH8A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022568.4. 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 | 1 | 2 | |||
| missense | 50 | 3 | 1 | 54 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 50 | 4 | 2 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_072090.1 | 7 | MANE Select | |
| Ensembl | ENSP00000265605.2 | 7 | MANE Select | |
| RefSeq | NP_001180409.1 | 6 | Standard | |
| RefSeq | NP_739577.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| aldh8a1 | Danio rerio | Structure: liver Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- RA biosynthesis pathway
- Signaling by Retinoic Acid
- Signaling by Nuclear Receptors
Biological Process
- retinoic acid metabolic process
- retinal metabolic process
- 9-cis-retinoic acid biosynthetic process
- oxidation-reduction process
Molecular Function
- retinal dehydrogenase activity
Cellular Component
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265605
- Coding exons
- 7
- Length
- 32733
- Individuals with no LoFs
- 125684
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 64
- Defined
- 125748
- p
- 0.000255
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.495 | 268 | 292 | 0.918 | 0.0000172 | 3183 |
| Missense (PolyPhen) | 111 | 128.43 | 0.86426 | 1329 | ||
| Synonymous | 0.497 | 115 | 122 | 0.943 | 0.00000835 | 972 |
| Loss of Function | 0.0524 | 18 | 18.2 | 0.987 | 7.72e-7 | 233 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00069 | 0.00069 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Converts 9-cis-retinal to 9-cis-retinoic acid. Has lower activity towards 13-cis-retinal. Has much lower activity towards all-trans-retinal. Has highest activity with benzaldehyde and decanal (in vitro). Has a preference for NAD, but shows considerable activity with NADP (in vitro). {ECO:0000269|PubMed:11007799}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.824
- RVIS EVS
- -0.57
- RVIS percentile EVS
- 18.9
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.296
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |