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Protein / target

Polyprenal reductase

Encoded bySRD5A3Q9H8P0Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+)

Strongest disease association

SRD5A3-congenital disorder of glycosylation

Via encoding gene SRD5A3 · Genetic evidence · score 0.89

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Plays a key role in early steps of protein N-linked glycosylation by being involved in the conversion of polyprenol into dolichol.

View complete UniProt function annotation

Plays a key role in early steps of protein N-linked glycosylation by being involved in the conversion of polyprenol into dolichol (PubMed:20637498, PubMed:38821050). Acts as a polyprenal reductase that mediates the reduction of polyprenal into dolichal in a NADP-dependent mechanism (PubMed:38821050). Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation (PubMed:20637498, PubMed:38821050). Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT) (PubMed:17986282, PubMed:26855069)

Subcellular location

Endoplasmic reticulum membrane
Domains and Gene Ontology detail (10)

Gene Ontology

  • Cendoplasmic reticulum
  • Cendoplasmic reticulum membrane
  • F3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity
  • F3-oxo-5-alpha-steroid 4-dehydrogenase activity
  • Foxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor
  • Fpolyprenal reductase activity
  • Pandrogen biosynthetic process
  • Pdolichol-linked oligosaccharide biosynthetic process
  • Pdolichyl monophosphate biosynthetic process
  • Ppolyprenol catabolic process

318 aa · 37 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Metabolic enzyme activityGO
View supporting evidence

Metabolic enzyme activity

  • ·3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity
  • ·3-oxo-5-alpha-steroid 4-dehydrogenase activity
  • ·oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor
View underlying pathways (3)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

SRD5A1DOLKAKR1C3AKR1C4HSD3B2AKR1C2CYP17A1SRD5A2HSD17B2AKR1C1SRD5A3

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Neoplasms1 medicine

2 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

abiraterone
ApprovedInhibitor

Steroid 5-alpha-reductase inhibitor

Indicated for Neoplasms

Acts on a complex — shared with SRD5A1, SRD5A2 · 1 of 5 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene SRD5A3

Gene-level evidence surfaced through the gene SRD5A3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

SRD5A3-congenital disorder of glycosylation
0.89Well supported

Genetic evidence dominant · Open Targets 0.83

Kahrizi syndrome
0.85Well supported

Genetic evidence dominant · Open Targets 0.74

Benign prostatic hyperplasia
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Prostatic Neoplasms
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Prostate carcinoma
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

View evidence synthesis (5)
SRD5A3-congenital disorder of glycosylationWell supported
0.89
agreement 0.751.00
Genetic99%Literature1%Genetic literaturedup

Open Targets aggregate 0.83 · 2 independent evidence families · 1 not counted as duplicate

Kahrizi syndromeWell supported
0.85
agreement 0.710.99
Genetic99%Literature1%Genetic literaturedup

Open Targets aggregate 0.74 · 2 independent evidence families · 1 not counted as duplicate

Benign prostatic hyperplasiaModerately supported
0.74
agreement 0.590.90
Clinical92%Literature8%

Open Targets aggregate 0.60 · 2 independent evidence families

Prostatic NeoplasmsModerately supported
0.69
agreement 0.540.85
Clinical95%Literature5%

Open Targets aggregate 0.56 · 2 independent evidence families

Prostate carcinomaModerately supported
0.68
agreement 0.530.84
Clinical94%Literature6%

Open Targets aggregate 0.55 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
SRD5A3-congenital disorder of glycosylation0.83
Kahrizi syndrome0.74
Benign prostatic hyperplasia0.60
Prostatic Neoplasms0.56
Prostate carcinoma0.55
Alopecia0.50
Neurodegenerative Diseases0.50
Congenital disorder of glycosylation0.46
Genetic Diseases, Inborn0.41

Drug development

2 compounds recorded · 2 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (2)
DUTASTERIDEApproval
ABIRATERONEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Druggable Family support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot sigp or tmhmm and human protein atlas loc) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
SM · Approved DrugSM · Druggable FamilyAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database Ubiquitination

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ClinicalTrials.gov via the drug-target graph.

What's happening now

11

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2024-12-11
    AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients.

    Nature communications · 2024 · 11 citations · Europe PMC · via abiraterone

  2. New publication2024-12-01
    Luteinizing hormone-releasing hormone receptor agonists and antagonists in prostate cancer: effects on long-term survival and combined therapy with next-generation hormonal agents.

    Cancer biology & medicine · 2024 · 9 citations · Europe PMC · via abiraterone

  3. New publication2024-09-01
    Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration-Resistant Prostate Cancer.

    Clinical cancer research : an official journal of the American Association for Cancer Research · 2024 · 19 citations · Europe PMC · via abiraterone

  4. New publication2023-02-16
    Rucaparib or Physician's Choice in Metastatic Prostate Cancer.

    The New England journal of medicine · 2023 · 332 citations · Europe PMC · via abiraterone

  5. Regulatory approval2021-08-20

    Approval: Abiraterone Mylan (EMA)

    ema · regulatory · ema · via abiraterone

  6. Regulatory approval2021-06-24

    Approval: Abiraterone Krka (EMA)

    ema · regulatory · ema · via abiraterone

  7. Regulatory approval2021-04-26

    Approval: Abiraterone Accord (EMA)

    ema · regulatory · ema · via abiraterone

  8. New publication2020-04-28
    Olaparib for Metastatic Castration-Resistant Prostate Cancer.

    The New England journal of medicine · 2020 · 1,688 citations · Europe PMC · via abiraterone

  9. New publication2019-09-30
    Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer.

    The New England journal of medicine · 2019 · 439 citations · Europe PMC · via abiraterone

  10. New publication2019-02-06
    Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial.

    The Lancet. Oncology · 2019 · 288 citations · Europe PMC · via abiraterone

  11. Accelerated approval granted2011-09-05

    Accelerated approval: Zytiga (EMA)

    ema · regulatory · ema · via abiraterone

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.