AKR7A2
protein-codingaldo-keto reductase family 7 member A2, the group of Aldo-keto reductases
Gene summary
The protein encoded by this gene belongs to the aldo/keto reductase (AKR) superfamily and AKR7 family, which are involved in the detoxification of aldehydes and ketones. The AKR7 family consists of 3 genes that are present in a cluster on the p arm of chromosome 1. This protein, thought to be localized in the golgi, catalyzes the NADPH-dependent reduction of succinic semialdehyde to the endogenous neuromodulator, gamma-hydroxybutyrate. It may also function as a detoxication enzyme in the reduction of aflatoxin B1 and 2-carboxybenzaldehyde. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.2 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 AKR7A2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003689.4. 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 | 0 | |||||
| missense | 67 | 2 | 1 | 70 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 71 | 2 | 1 | 74 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003680.2 | 7 | MANE Select | |
| Ensembl | ENSP00000235835.3 | 7 | MANE Select | |
| RefSeq | NP_001307908.1 | 6 | Standard | |
| Ensembl | ENSP00000339084.5 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
- Aflatoxin B1 metabolism
- Metapathway biotransformation Phase I and II
- oxidative stress induced gene expression via nrf2
- Biological oxidations
Biological Process
- carbohydrate metabolic process
- cellular aldehyde metabolic process
- xenobiotic metabolic process
- electron transport chain
- daunorubicin metabolic process
Molecular Function
- alditol:NADP+ 1-oxidoreductase activity
- aldo-keto reductase (NADP) activity
- protein binding
- electron transfer activity
- phenanthrene-9,10-epoxide hydrolase activity
Cellular Component
- Golgi apparatus
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000235835
- Coding exons
- 7
- Length
- 8182
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125748
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.417 | 211 | 195 | 1.08 | 0.0000117 | 2283 |
| Missense (PolyPhen) | 69 | 60.752 | 1.1358 | 723 | ||
| Synonymous | -0.854 | 99 | 88.8 | 1.12 | 0.00000605 | 730 |
| Loss of Function | 0.0298 | 15 | 15.1 | 0.992 | 6.70e-7 | 180 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000055 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2- nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen. {ECO:0000269|PubMed:17591773, ECO:0000269|PubMed:9576847}.;
Intolerance Scores
- LoFtool
- 0.720
- RVIS EVS
- 0.71
- RVIS percentile EVS
- 85.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.926
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |