HSD3B1
Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- and Steroid Delta-Isomerase 1
Gene Information Card
| Symbol | HSD3B1 |
|---|---|
| Full Name | Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- and Steroid Delta-Isomerase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p12 |
| NCBI Gene ID | 3283 ncbi.nlm.nih.gov/gene/3283 |
| Ensembl ID | ENSG00000133895 |
| UniProt ID | P14060 |
| OMIM ID | 109715 |
| HGNC ID | 5217 |
| Aliases | 3β-HSD, HSD3B, HSDB3, SDR11E1 |
Description
HSD3B1 encodes the 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase type 1 enzyme, which catalyzes the conversion of Δ5-3β-hydroxysteroids (e.g., pregnenolone, 17α-hydroxypregnenolone, dehydroepiandrosterone) to Δ4-3-ketosteroids (progesterone, 17α-hydroxyprogesterone, androstenedione). This enzyme is essential for the biosynthesis of all classes of steroid hormones: glucocorticoids, mineralocorticoids, and sex steroids. It is expressed primarily in the placenta, adrenal cortex, and peripheral tissues such as skin and prostate.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital adrenal hyperplasia (CAH) due to 3β-hydroxysteroid dehydrogenase deficiency | Loss-of-function mutations in HSD3B1 impair conversion of Δ5 to Δ4 steroids, leading to impaired cortisol and aldosterone synthesis with androgen excess in utero. | OMIM #201810; ClinVar pathogenic variants |
| Prostate cancer (castration-resistant) | Gain-of-function variant HSD3B1(1245A>C) increases conversion of DHEA to DHT, enabling androgen synthesis from adrenal precursors and resistance to androgen deprivation therapy. | COSMIC; ClinVar; multiple clinical studies |
| Polycystic ovary syndrome (PCOS) | Altered HSD3B1 activity may contribute to hyperandrogenism via increased conversion of Δ5 androgens. | Association studies; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 12.5 | Medium |
| Placenta | 45.2 | High |
| Skin | 8.3 | Low |
| Prostate | 6.1 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H295R (adrenocortical) | 35.0 | High expression |
| LNCaP (prostate) | 2.5 | Low expression |
| MCF-7 (breast) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1245A>C (p.Thr415Ala) | SNV | ~10% in prostate cancer cohorts | Gain-of-function; increased DHEA to DHT conversion |
| c.35G>A (p.Arg12His) | SNV | Rare | Loss-of-function; associated with CAH |
| c.424G>A (p.Gly142Arg) | SNV | Rare | Loss-of-function; associated with CAH |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg12His and p.Gly142Arg reduce or abolish enzyme activity, leading to congenital adrenal hyperplasia with impaired steroidogenesis.
Gain of Function (GOF)
The p.Thr415Ala variant enhances the conversion of DHEA to androstenedione, increasing dihydrotestosterone synthesis and promoting castration-resistant prostate cancer.
Dominant Negative (DN)
No dominant-negative mutations have been reported for HSD3B1.
View complete mutation data：
Gene Ontology (GO)
| • 3-beta-hydroxy-delta5-steroid dehydrogenase activity (GO:0003854) | • steroid delta-isomerase activity (GO:0004769) |
| • steroid biosynthetic process (GO:0006694) | • C21-steroid hormone biosynthetic process (GO:0032346) |
| • androgen biosynthetic process (GO:0006702) | • endoplasmic reticulum membrane (GO:0005789) |
Pathways
• Steroid hormone biosynthesis (KEGG hsa00140)
• Metabolism of steroids (Reactome R-HSA-196071)
• Androgen biosynthesis (Reactome R-HSA-196015)
Protein Summary
HSD3B1 encodes a 42 kDa membrane-bound enzyme of the short-chain dehydrogenase/reductase superfamily. It is localized to the endoplasmic reticulum and mitochondria. The enzyme catalyzes two sequential reactions: 3β-hydroxysteroid dehydrogenase and Δ5-Δ4 isomerase, converting Δ5-3β-hydroxysteroids to Δ4-3-ketosteroids. This is a rate-limiting step in steroidogenesis. The type 1 isozyme (HSD3B1) is predominantly expressed in placenta and peripheral tissues, whereas type 2 (HSD3B2) is adrenal- and gonad-specific. Gain-of-function variant p.Thr415Ala is associated with poor outcomes in prostate cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HSD3B1 Knockout HEK293 Cell Line | EDJ-KQ50365 | Human | 3283 | Details Get a Quote |
| HSD3B1 Knockout HeLa Cell Line | EDJ-KQ53574 | Human | 3283 | Details Get a Quote |
| HSD3B1 Knockout A-549 Cell Line | EDJ-KQ62040 | Human | 3283 | Details Get a Quote |
| HSD3B1 Knockout HCT 116 Cell Line | EDJ-KQ70522 | Human | 3283 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
