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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SRD5A1
steroid 5 alpha-reductase 1
Chromosome 5 · 5p15.31
NCBI Gene: 6715Ensembl: ENSG00000145545.14HGNC: HGNC:11284UniProt: B7Z4D8
109PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein binding3-oxo-5-alpha-steroid 4-dehydrogenase activityandrogen biosynthetic processmale gonad developmentbenign prostatic hyperplasiaprostate carcinomaprostate canceralopecia
✦AI Summary

SRD5A1 encodes steroid 5α-reductase type 1, a membrane-bound enzyme catalyzing the conversion of testosterone to 5α-dihydrotestosterone (DHT) and progesterone/corticosterone to their 5α-reduced metabolites 1. This enzymatic activity is essential for amplifying androgen receptor signaling in target tissues 1. The enzyme contains seven transmembrane helices with a conserved catalytic domain, and notably, human SRD5A1 mRNA undergoes triple-frame translation producing multiple proteoforms, a feature specific to primates 2. In reproductive physiology, SRD5A1 expression is dynamically regulated during reproductive phases and responds to gonadotropin-releasing hormone stimulation 3. During human labor, SRD5A1 expression decreases significantly in chorioamniotic membranes, indicating tissue-specific roles in progesterone metabolism 4. Clinically, SRD5A1 polymorphisms associate with impaired glucose homeostasis in males, with the rs1691053 CC genotype showing increased odds for impaired fasting glucose in interaction with testosterone levels 5. In prostate cancer, SRD5A1 promotes disease progression by elevating intracellular DHT and enhancing androgen receptor expression; combined inhibition of SRD5A1 and BRD4 shows enhanced therapeutic potential 6. Additionally, targeting SRD5A1 suppression induces autophagy in colorectal cancer through PI3K/AKT pathway inhibition 7.

Sources cited
1
SRD5A1 converts testosterone to DHT and epitestosterone to 5α-dihydroepitestosterone, enhancing androgen receptor signaling
PMID: 38582131
2
Human SRD5A1 mRNA undergoes triple-frame translation producing multiple proteoforms, a primate-specific feature
PMID: 39764142
3
SRD5A1 expression is dynamically regulated during reproductive phases and responds to GnRH stimulation
PMID: 37945678
4
SRD5A1 expression decreases in chorioamniotic membranes during labor, indicating tissue-specific progesterone metabolism roles
PMID: 18770491
5
SRD5A1 rs1691053 polymorphism associates with impaired fasting glucose in males, with interaction effects involving testosterone
PMID: 31870594
6
SRD5A1 promotes prostate cancer progression by elevating DHT and androgen receptor expression; combined SRD5A1 and BRD4 inhibition enhances therapeutic effect
PMID: 41423110
7
SRD5A1 targeting suppresses colorectal cancer through autophagy induction via PI3K/AKT pathway inhibition
PMID: 40756270
Disease Associationsⓘ20
benign prostatic hyperplasiaOpen Targets
0.60Moderate
prostate carcinomaOpen Targets
0.56Moderate
prostate cancerOpen Targets
0.53Moderate
alopeciaOpen Targets
0.48Moderate
androgenetic alopeciaOpen Targets
0.47Moderate
prostate neoplasmOpen Targets
0.46Moderate
neoplasmOpen Targets
0.41Moderate
prostate adenocarcinomaOpen Targets
0.35Weak
hypertrophic cardiomyopathyOpen Targets
0.34Weak
mixed connective tissue diseaseOpen Targets
0.29Weak
hypogonadismOpen Targets
0.29Weak
alcohol abuseOpen Targets
0.18Weak
prostatitisOpen Targets
0.18Weak
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.15Weak
metastatic prostate cancerOpen Targets
0.11Weak
DNA methylationOpen Targets
0.09Suggestive
bipolar disorderOpen Targets
0.08Suggestive
trigeminal nerve diseaseOpen Targets
0.08Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
ABIRATERONEApproved
Androgen Receptor antagonist
prostate cancer
DUTASTERIDEApproved
Steroid 5-alpha-reductase inhibitor
androgenetic alopecia
Related Genes
AKR1C4Protein interaction99%CYP21A2Protein interaction99%AKR1C1Protein interaction99%HSD11B1Protein interaction99%HSD11B2Protein interaction99%AKR1C3Protein interaction98%
Tissue Expression6 tissues
Liver
100%
Brain
69%
Ovary
13%
Bone Marrow
8%
Lung
7%
Heart
7%
Gene Interaction Network
Click a node to explore
SRD5A1AKR1C4CYP21A2AKR1C1HSD11B1HSD11B2AKR1C3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P18405
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.27LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.85 [0.58–1.27]
RankingsWhere SRD5A1 stands among ~20K protein-coding genes
  • #4,385of 20,598
    Most Researched109 · top quartile
  • #595of 1,025
    FDA-Approved Drug Targets2
  • #13,420of 17,882
    Most Constrained (LOEUF)1.27
Genes detectedSRD5A1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Associations of SRD5A1 gene variants and testosterone with dysglycemia: Henan Rural Cohort study.
PMID: 31870594
Nutr Metab Cardiovasc Dis · 2020
1.00
2
5α-reduction of epitestosterone is catalysed by human SRD5A1 and SRD5A2 and increases androgen receptor transactivation.
PMID: 38582131
J Steroid Biochem Mol Biol · 2024
0.90
3
Cloning, computational analysis and expression profiling of steroid 5 alpha-reductase 1 (SRD5A1) gene during reproductive phases and ovatide stimulation in endangered catfish, Clarias magur.
PMID: 37945678
Sci Rep · 2023
0.80
4
AKR1C1 and SRD5A1 messenger RNA expression at term in the human myometrium and chorioamniotic membranes.
PMID: 18770491
Am J Perinatol · 2008
0.70
5
Restraining SRD5A1 combined with BRD4 inhibitor delaying prostate cancer progression by decreasing AR expression.
PMID: 41423110
Int J Biol Macromol · 2026
0.60