AKR1C4: Aldo-Keto Reductase Family 1 Member C4
A key enzyme in steroid hormone metabolism and bile acid synthesis
Gene Information Card
| Symbol | AKR1C4 |
|---|---|
| Full Name | Aldo-Keto Reductase Family 1 Member C4 |
| Gene Type | Protein coding |
| Chromosomal Location | 10p15.1 |
| NCBI Gene ID | 1109 ncbi.nlm.nih.gov/gene/1109 |
| Ensembl ID | ENSG00000198010 |
| UniProt ID | P17516 |
| OMIM ID | 600451 |
| HGNC ID | 386 |
| Aliases | CHDR, DD4, HAKRA, 3-alpha-HSD, C11-HSD, dihydrodiol dehydrogenase 4 |
Description
AKR1C4 encodes a member of the aldo-keto reductase superfamily, specifically the 3-alpha-hydroxysteroid dehydrogenase type 1 (3α-HSD1). This enzyme is primarily expressed in the liver and plays a critical role in the metabolism of steroid hormones (e.g., androgens, progestins) and bile acid biosynthesis. It catalyzes the reduction of ketosteroids to hydroxysteroids, modulating hormone activity and detoxifying xenobiotics.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cholestasis | Impaired bile acid metabolism due to reduced AKR1C4 activity may contribute to bile acid accumulation | PMID: 12441305 |
| Prostate cancer | Altered androgen metabolism via AKR1C4 may influence hormone-sensitive cancer progression | PMID: 15634693 |
| Polycystic ovary syndrome (PCOS) | Variants in AKR1C4 may affect steroid hormone clearance, contributing to hyperandrogenism | PMID: 21937676 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 37.2 | High |
| Adrenal gland | 12.1 | Medium |
| Kidney | 8.5 | Medium |
| Small intestine | 4.3 | Low |
| Prostate | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.6 | Hepatocellular carcinoma cell line |
| Huh-7 | 12.8 | Hepatoma cell line |
| LNCaP | 1.2 | Prostate cancer cell line |
| MCF-7 | 0.5 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.73G>A (p.Gly25Arg) | Missense | <0.01 | Reduced enzyme activity in vitro |
| c.445C>T (p.Arg149Cys) | Missense | <0.01 | Altered substrate specificity |
| c.877G>A (p.Gly293Arg) | Missense | <0.01 | Decreased stability and activity |
Mutation functional classification
Loss of Function (LOF)
Missense mutations such as p.Gly25Arg and p.Gly293Arg reduce catalytic activity, impairing steroid and bile acid metabolism.
Gain of Function (GOF)
No gain-of-function mutations have been reported for AKR1C4.
Dominant Negative (DN)
No dominant-negative effects have been documented.
View complete mutation data：
Gene Ontology (GO)
| • Aldo-keto reductase (NADPH) activity (GO:0004032) | • 3-alpha-hydroxysteroid dehydrogenase (B-specific) activity (GO:0047045) |
| • Oxidoreductase activity (GO:0016491) | • Cytoplasm (GO:0005737) |
| • Bile acid biosynthetic process (GO:0006699) | • Steroid metabolic process (GO:0008202) |
Pathways
• Bile acid biosynthesis (Reactome: R-HSA-194068)
• Androgen and estrogen metabolism (KEGG: hsa00150)
• Metabolism of steroids (Reactome: R-HSA-8957322)
Protein Summary
AKR1C4 is a 323-amino acid monomeric enzyme (37 kDa) localized in the cytoplasm. It uses NADPH as a cofactor to reduce ketone groups on steroids and bile acid intermediates. The protein structure includes a (β/α)8 barrel fold typical of aldo-keto reductases. It is highly expressed in the liver and contributes to the inactivation of circulating androgens and progestins, as well as the conversion of 7-ketolithocholic acid to chenodeoxycholic acid in bile acid synthesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKR1C4 Knockout HEK293 Cell Line | EDJ-KQ4264 | Human | 1109 | Details Get a Quote |
| AKR1C4 Knockout A-549 Cell Line | EDJ-KQ26745 | Human | 1109 | Details Get a Quote |
| AKR1C4 Knockout HeLa Cell Line | EDJ-KQ52887 | Human | 1109 | Details Get a Quote |
| AKR1C4 Knockout HCT 116 Cell Line | EDJ-KQ69852 | Human | 1109 | Details Get a Quote |
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