ALDH1A2
protein-codingaldehyde dehydrogenase 1 family member A2, the group of Aldehyde dehydrogenases
Gene summary
This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~544.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859571
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0859571
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0859571
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Musculoskeletal
Intervention: Cardiovascular
Rationale: The condition may involve complex cardiovascular anomalies, and awareness may allow early surgical and related management if indicated
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ALDH1A2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003888.4. 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 | 8 | 2 | 10 | |||
| missense | 4 | 35 | 2 | 1 | 42 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 4 | 0 | 37 | 10 | 3 | 54 |
Highest pathogenic variant AF is 0.000014249056
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003879.2 | 13 | MANE Select | |
| Ensembl | ENSP00000249750.4 | 13 | MANE Select | |
| RefSeq | NP_001193826.1 | 13 | Standard | |
| RefSeq | NP_733797.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| aldh1a2 | Danio rerio | Structure: hyohyoideus Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Retinol metabolism - Homo sapiens (human)
- Vitamin A Deficiency
- Retinol Metabolism
- Ethanol effects on histone modifications
- Tryptophan metabolism
Biological Process
- blood vessel development
- kidney development
- liver development
- regulation of endothelial cell proliferation
- heart morphogenesis
Molecular Function
- retinal dehydrogenase activity
- 3-chloroallyl aldehyde dehydrogenase activity
- aldehyde dehydrogenase (NAD) activity
- retinal binding
Cellular Component
- cytoplasm
- cytosol
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000249750
- Coding exons
- 13
- Length
- 544444
- 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 | 1.44 | 215 | 283 | 0.759 | 0.0000153 | 3399 |
| Missense (PolyPhen) | 83 | 146.21 | 0.56767 | 1799 | ||
| Synonymous | -1.75 | 128 | 105 | 1.22 | 0.00000572 | 1010 |
| Loss of Function | 3.69 | 6 | 26.5 | 0.226 | 0.00000130 | 325 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000065 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Does metabolize octanal and decanal but does not metabolize citral, benzaldehyde, acetaldehyde and propanal efficiently (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.220
Intolerance Scores
- LoFtool
- 0.302
- RVIS EVS
- -0.45
- RVIS percentile EVS
- 24.33
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.835
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | High |