AKR1A1
protein-codingaldo-keto reductase family 1 member A1, the group of Aldo-keto reductases
Gene summary
This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member, also known as aldehyde reductase, is involved in the reduction of biogenic and xenobiotic aldehydes and is present in virtually every tissue. Multiple alternatively spliced transcript variants of this gene exist, all encoding the same protein. [provided by RefSeq, Jan 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.5 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 AKR1A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153326.3. 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 | ||||
| missense | 34 | 1 | 35 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 39 | 2 | 1 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_697021.1 | 8 | MANE Select | |
| Ensembl | ENSP00000312606.4 | 8 | MANE Select | |
| RefSeq | NP_001189342.1 | 8 | Standard | |
| RefSeq | NP_001189343.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- Glycerolipid metabolism - Homo sapiens (human)
- Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics
- Doxorubicin Pathway, Pharmacokinetics
- Pentose and glucuronate interconversions - Homo sapiens (human)
Biological Process
- glucose metabolic process
- cellular aldehyde metabolic process
- glucuronate catabolic process to xylulose 5-phosphate
- L-ascorbic acid biosynthetic process
- electron transport chain
Molecular Function
- alditol:NADP+ 1-oxidoreductase activity
- aldo-keto reductase (NADP) activity
- protein binding
- alcohol dehydrogenase (NADP+) activity
- electron transfer activity
Cellular Component
- extracellular space
- cytosol
- apical plasma membrane
- synapse
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372070
- Coding exons
- 8
- Length
- 19507
- Individuals with no LoFs
- 125627
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 120
- Defined
- 125747
- p
- 0.000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0212 | 191 | 190 | 1.00 | 0.0000108 | 2106 |
| Missense (PolyPhen) | 62 | 58.37 | 1.0622 | 701 | ||
| Synonymous | 0.529 | 67 | 72.7 | 0.921 | 0.00000383 | 658 |
| Loss of Function | 1.19 | 12 | 17.3 | 0.692 | 8.91e-7 | 190 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.00064 | 0.00064 | rare |
| South Asian | 0.00049 | 0.00049 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyde to glycerol. Has broad substrate specificity. In vitro substrates include succinic semialdehyde, 4- nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D- glucuronic acid. Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN). {ECO:0000269|PubMed:10510318, ECO:0000269|PubMed:11306097, ECO:0000269|PubMed:18276838}.;
Recessive Scores
- pRec
- 0.223
Intolerance Scores
- LoFtool
- 0.985
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |