AKR1C3
protein-codingaldo-keto reductase family 1 member C3, 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. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
- HSD17B5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~72.3 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 AKR1C3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003739.6. 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 | 1 | 3 | |||
| missense | 64 | 3 | 3 | 70 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 67 | 4 | 4 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003730.4 | 9 | MANE Select | |
| Ensembl | ENSP00000369927.3 | 9 | MANE Select | |
| RefSeq | NP_001240837.1 | 9 | Standard | |
| RefSeq | NP_001240838.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Folate biosynthesis - Homo sapiens (human)
- Steroid hormone biosynthesis - Homo sapiens (human)
- Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics
- Arachidonic acid metabolism - Homo sapiens (human)
- Doxorubicin Pathway, Pharmacokinetics
Biological Process
- obsolete protein import into nucleus, translocation
- retinoid metabolic process
- prostaglandin metabolic process
- G protein-coupled receptor signaling pathway
- response to nutrient
Molecular Function
- retinal dehydrogenase activity
- alditol:NADP+ 1-oxidoreductase activity
- aldo-keto reductase (NADP) activity
- retinol dehydrogenase activity
- alcohol dehydrogenase (NADP+) activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380554
- Coding exons
- 9
- Length
- 72333
- Individuals with no LoFs
- 125194
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 551
- Defined
- 125748
- p
- 0.00221
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.81 | 237 | 171 | 1.39 | 0.00000872 | 2105 |
| Missense (PolyPhen) | 82 | 52.055 | 1.5753 | 692 | ||
| Synonymous | -1.82 | 80 | 61.8 | 1.29 | 0.00000302 | 600 |
| Loss of Function | -1.83 | 30 | 21.0 | 1.43 | 0.00000139 | 223 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.014 | 0.014 | notable |
| Latino/Admixed American | 0.0013 | 0.0013 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0046 | 0.0046 | notable |
| Finnish | 0.00046 | 0.00046 | rare |
| European (Non-Finnish) | 0.0011 | 0.0011 | notable |
| South Asian | 0.0017 | 0.0017 | notable |
| Other | 0.0020 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta- PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.;
Recessive Scores
- pRec
- 0.307
Intolerance Scores
- LoFtool
- 0.973
- RVIS EVS
- 0.78
- RVIS percentile EVS
- 87.14
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.985
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |