AKR1C3 (Aldo-Keto Reductase Family 1 Member C3)
A key enzyme in steroid hormone metabolism and prostaglandin synthesis, implicated in hormone-dependent cancers and endocrine disorders.
Gene Information Card
| Symbol | AKR1C3 |
|---|---|
| Full Name | Aldo-Keto Reductase Family 1 Member C3 |
| Gene Type | Protein coding |
| Chromosomal Location | 10p15.1 |
| NCBI Gene ID | 8644 ncbi.nlm.nih.gov/gene/8644 |
| Ensembl ID | ENSG00000196139 |
| UniProt ID | P42330 |
| OMIM ID | 603966 |
| HGNC ID | 386 |
| Aliases | 17β-HSD5, HSD17B5, DD3, HA1753, PGFS, hPGFS |
Description
AKR1C3 encodes a member of the aldo-keto reductase superfamily. The enzyme functions as a 17β-hydroxysteroid dehydrogenase (17β-HSD5), catalyzing the reduction of androstenedione to testosterone and estrone to 17β-estradiol. It also acts as a prostaglandin F synthase, converting PGH2 to PGF2α and PGD2 to 9α,11β-PGF2. AKR1C3 is involved in steroid hormone metabolism, prostaglandin synthesis, and xenobiotic detoxification. Overexpression is linked to hormone-dependent cancers (prostate, breast, endometrial) and endocrine disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Overexpression increases intratumoral testosterone and dihydrotestosterone, promoting androgen receptor signaling. | PMID: 20053711, COSMIC |
| Breast cancer | Converts estrone to estradiol, enhancing estrogen receptor signaling. | PMID: 23327927 |
| Endometriosis | Elevated AKR1C3 activity increases local estradiol production, supporting lesion growth. | PMID: 18436710 |
| Acute myeloid leukemia | AKR1C3 contributes to chemoresistance by inactivating anthracyclines. | PMID: 20053711 |
| Castration-resistant prostate cancer | Upregulation of AKR1C3 sustains androgen synthesis despite androgen deprivation therapy. | PMID: 20053711 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adrenal gland | 8.3 | Medium |
| Prostate | 6.7 | Medium |
| Breast | 4.2 | Low |
| Endometrium | 3.8 | Low |
| Kidney | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LNCaP (prostate cancer) | 15.2 | High expression; androgen-sensitive |
| MCF-7 (breast cancer) | 8.9 | Medium expression; estrogen receptor-positive |
| HepG2 (liver cancer) | 6.4 | Medium expression |
| K562 (leukemia) | 1.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gln5His | Missense | <0.1% (COSMIC) | Unknown functional effect |
| p.Arg258Cys | Missense | <0.1% (ClinVar) | Likely benign |
| p.Val291Ile | Missense | <0.1% (COSMIC) | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in major databases.
Gain of Function (GOF)
Overexpression (not mutation) is the primary gain-of-function mechanism in cancer.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003854 - 3-alpha-hydroxysteroid dehydrogenase (B-specific) activity | • GO:0004303 - estradiol 17-beta-dehydrogenase activity |
| • GO:0016229 - prostaglandin-F synthase activity | • GO:0006695 - cholesterol biosynthetic process |
| • GO:0008202 - steroid metabolic process | • GO:0005576 - extracellular region |
| • GO:0005829 - cytosol |
Pathways
• Steroid hormone biosynthesis (KEGG: hsa00140)
• Prostaglandin synthesis and metabolism (Reactome: R-HSA-2162123)
• Androgen and estrogen metabolism (Reactome: R-HSA-196854)
Protein Summary
AKR1C3 is a 323-amino-acid monomeric enzyme with a typical (α/β)8 barrel structure. It uses NADP(H) as a cofactor to catalyze the reduction of ketones and aldehydes. The enzyme is primarily cytosolic and expressed in steroidogenic tissues (liver, adrenal, prostate) and hormone-responsive tissues. Its dual role in steroid hormone activation and prostaglandin synthesis makes it a therapeutic target for hormone-dependent cancers and inflammatory conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKR1C3 Knockout HEK293 Cell Line | EDJ-KQ1964 | Human | 8644 | Details Get a Quote |
| AKR1C3 Knockout A-549 Cell Line | EDJ-KQ21929 | Human | 8644 | Details Get a Quote |
| AKR1C3 Knockout HCT 116 Cell Line | EDJ-KQ21930 | Human | 8644 | Details Get a Quote |
| AKR1C3 Knockout HeLa Cell Line | EDJ-KQ21931 | Human | 8644 | Details Get a Quote |
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