AKR1B15
protein-codingaldo-keto reductase family 1 member B15, the group of Aldo-keto reductases
Gene summary
Enables estradiol 17-beta-dehydrogenase [NAD(P)+] activity. Predicted to be involved in estrogen biosynthetic process. Located in cytosol; mitochondrion; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.8 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 AKR1B15 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001080538.3. 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 | 58 | 5 | 63 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 62 | 5 | 2 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001074007.2 | 10 | MANE Select | |
| Ensembl | ENSP00000389289.1 | 10 | MANE Select | |
| RefSeq | NP_001354749.1 | 10 | Standard | |
| RefSeq | NP_001354750.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- Metabolism
- Estrogen biosynthesis
- Metabolism of steroid hormones
- Metabolism of steroids
Biological Process
- estrogen biosynthetic process
- oxidation-reduction process
Molecular Function
- alditol:NADP+ 1-oxidoreductase activity
- estradiol 17-beta-dehydrogenase activity
- alcohol dehydrogenase (NADP+) activity
- oxidoreductase activity
Cellular Component
- mitochondrion
- mitochondrial matrix
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000457545
- Coding exons
- 10
- Length
- 30740
- Individuals with no LoFs
- 125658
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 84
- Defined
- 125743
- p
- 0.000338
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.933 | 218 | 183 | 1.19 | 0.00000924 | 2278 |
| Missense (PolyPhen) | 62 | 61.66 | 1.0055 | 848 | ||
| Synonymous | -0.418 | 72 | 67.6 | 1.06 | 0.00000365 | 611 |
| Loss of Function | -2.17 | 27 | 17.3 | 1.56 | 7.28e-7 | 224 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0010 | 0.0010 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00034 | 0.00033 | rare |
| South Asian | 0.00052 | 0.00049 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Isoform 1: Mainly acts as a reductive enzyme that catalyzes the reduction of androgens and estrogens with high positional selectivity (shows 17-beta-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoAs. Has a strong selectivity towards NADP(H) (PubMed:25577493). {ECO:0000269|PubMed:21276782, ECO:0000269|PubMed:25577493}.;
Intolerance Scores
- LoFtool
- 0.894
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.69
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |