ALDH1A3
protein-codingaldehyde dehydrogenase 1 family member A3, the group of Aldehyde dehydrogenases
Gene summary
This gene encodes an aldehyde dehydrogenase enzyme that uses retinal as a substrate. Mutations in this gene have been associated with microphthalmia, isolated 8, and expression changes have also been detected in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
- ALDH6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~54.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014050
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014050
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0016764
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ALDH1A3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000693.4. 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 | 34 | 3 | 38 | ||
| missense | 5 | 10 | 50 | 4 | 69 | |
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 3 | 2 | 4 | 9 | ||
| Total | 14 | 14 | 55 | 38 | 3 | 124 |
Highest pathogenic variant AF is 0.000018585126
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000684.2 | 13 | MANE Select | |
| Ensembl | ENSP00000332256.5 | 13 | MANE Select | |
| RefSeq | NP_001280744.1 | 10 | Standard | |
| Ensembl | ENSP00000343294.6 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| aldh1a3 | Danio rerio | Structure: eye Quality: decreased size abnormal |
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
- optic cup morphogenesis involved in camera-type eye development
- retinoic acid biosynthetic process
- locomotory behavior
- nucleus accumbens development
- embryonic camera-type eye development
Molecular Function
- retinal dehydrogenase activity
- aldehyde dehydrogenase (NAD) activity
- aldehyde dehydrogenase [NAD(P)+] activity
- protein homodimerization activity
- thyroid hormone binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- plasma membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329841
- Coding exons
- 13
- Length
- 38913
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.24 | 192 | 301 | 0.637 | 0.0000180 | 3324 |
| Missense (PolyPhen) | 72 | 145.35 | 0.49537 | 1536 | ||
| Synonymous | 0.0733 | 122 | 123 | 0.992 | 0.00000828 | 1020 |
| Loss of Function | 3.31 | 6 | 23.2 | 0.259 | 9.79e-7 | 306 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: NAD-dependent aldehyde dehydrogenase that catalyzes the formation of retinoic acid (PubMed:27759097). Has high activity with all-trans retinal, and has much lower in vitro activity with acetaldehyde (PubMed:27759097). Required for the biosynthesis of normal levels of retinoic acid in the embryonic ocular and nasal regions; retinoic acid is required for normal embryonic development of the eye and the nasal region (By similarity). {ECO:0000250|UniProtKB:Q9JHW9, ECO:0000269|PubMed:27759097}.;
Recessive Scores
- pRec
- 0.268
Intolerance Scores
- LoFtool
- 0.606
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.72
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.715
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |