AKR1C1: Aldo-Keto Reductase Family 1 Member C1
A key enzyme in steroid hormone metabolism and prostaglandin synthesis, implicated in cancer and endocrine disorders.
Gene Information Card
| Symbol | AKR1C1 |
|---|---|
| Full Name | Aldo-Keto Reductase Family 1 Member C1 |
| Gene Type | protein-coding |
| Chromosomal Location | 10p15.1 |
| NCBI Gene ID | 1645 ncbi.nlm.nih.gov/gene/1645 |
| Ensembl ID | ENSG00000187134 |
| UniProt ID | Q04828 |
| OMIM ID | 600449 |
| HGNC ID | 384 |
| Aliases | DD1, DDH1, HAKRC, MBAB, 20-alpha-HSD, PGFS |
Description
AKR1C1 encodes a member of the aldo/keto reductase superfamily, which catalyzes the NADPH-dependent reduction of carbonyl groups. This enzyme functions as a 20-alpha-hydroxysteroid dehydrogenase (20-alpha-HSD), converting progesterone to its inactive metabolite 20-alpha-hydroxyprogesterone, and as a prostaglandin F synthase, reducing prostaglandin H2 to prostaglandin F2α. It plays a critical role in steroid hormone metabolism, prostaglandin synthesis, and detoxification of xenobiotics. Dysregulation of AKR1C1 is associated with hormone-sensitive cancers, endometriosis, and other endocrine-related conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Endometriosis | Altered progesterone metabolism via 20-alpha-HSD activity may contribute to progesterone resistance in endometrial tissue. | PMID: 21504852 |
| Prostate Cancer | Overexpression of AKR1C1 inactivates dihydrotestosterone, potentially modulating androgen signaling and disease progression. | PMID: 15604205 |
| Breast Cancer | Increased AKR1C1 expression correlates with poor prognosis and may promote tumor growth through prostaglandin F2α synthesis. | PMID: 19029981 |
| Non-Small Cell Lung Cancer | AKR1C1 upregulation is associated with chemoresistance and altered steroid metabolism. | PMID: 23549704 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Adrenal Gland | 6.7 | Low |
| Prostate | 5.1 | Low |
| Breast | 3.2 | Low |
| Endometrium | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Hepatocellular carcinoma cell line |
| MCF-7 | 4.5 | Breast cancer cell line |
| LNCaP | 3.8 | Prostate cancer cell line |
| A549 | 2.1 | Lung adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Initiation codon loss, likely loss of function |
| c.94C>T (p.Arg32Cys) | missense | <0.01% | Reduced catalytic activity |
| c.559G>A (p.Gly187Arg) | missense | <0.01% | Altered substrate specificity |
Mutation functional classification
Loss of Function (LOF)
Mutations affecting the NADPH-binding domain or catalytic residues (e.g., p.Arg32Cys) reduce enzyme activity.
Gain of Function (GOF)
Not well documented; overexpression rather than activating mutations is observed in cancers.
Dominant Negative (DN)
No known dominant-negative variants reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004033 - aldo-keto reductase (NADPH) activity | • GO:0004303 - estradiol 17-beta-dehydrogenase activity |
| • GO:0016229 - steroid dehydrogenase activity | • GO:0006694 - steroid biosynthetic process |
| • GO:0008202 - steroid metabolic process | • GO:0001516 - prostaglandin biosynthetic process |
| • GO:0005737 - cytoplasm |
Pathways
• Progesterone metabolism (Reactome: R-HSA-193048)
• Prostaglandin synthesis (Reactome: R-HSA-2162123)
• Androgen metabolism (Reactome: R-HSA-193144)
Protein Summary
AKR1C1 is a 323-amino-acid monomeric enzyme (37 kDa) that uses NADPH as a cofactor. Its three-dimensional structure comprises a (β/α)8-barrel fold typical of aldo-keto reductases. The active site contains a catalytic tetrad (Asp50, Tyr55, Lys84, His117) essential for hydride transfer. The enzyme exhibits broad substrate specificity, reducing steroids, prostaglandins, and xenobiotic aldehydes. Post-translational modifications include phosphorylation at Ser145, which modulates activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKR1C1 Knockout HEK293 Cell Line | EDJ-KQ2471 | Human | 1645 | Details Get a Quote |
| AKR1C1 Knockout A-549 Cell Line | EDJ-KQ23032 | Human | 1645 | Details Get a Quote |
| AKR1C1 Knockout HCT 116 Cell Line | EDJ-KQ23033 | Human | 1645 | Details Get a Quote |
| AKR1C1 Knockout HeLa Cell Line | EDJ-KQ23034 | Human | 1645 | Details Get a Quote |
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