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Protein / target

DNA-directed RNA polymerase I subunit RPA1

Encoded byPOLR1AO95602Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
1
Clinical candidates
2
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

DNA-directed RNA polymerase

Strongest disease association

Benign prostatic hyperplasia

Via encoding gene POLR1A · Genetic evidence · score 0.42

Therapeutic position

Clinically advancing 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

Catalytic core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates.

View complete UniProt function annotation

Catalytic core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Transcribes 47S pre-rRNAs from multicopy rRNA gene clusters, giving rise to 5.8S, 18S and 28S ribosomal RNAs (PubMed:11250903, PubMed:11283244, PubMed:16858408, PubMed:34671025, PubMed:34887565, PubMed:36271492). Pol I-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol I pre-initiation complex (PIC) is recruited by the selectivity factor 1 (SL1/TIF-IB) complex bound to the core promoter that precedes an rDNA repeat unit. The PIC assembly bends the promoter favoring the formation of the transcription bubble and promoter escape. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Highly processive, assembles in structures referred to as 'Miller trees' where many elongating Pol I complexes queue and transcribe the same rDNA coding regions. At terminator sequences downstream of the rDNA gene, PTRF interacts with Pol I and halts Pol I transcription leading to the release of the RNA transcript and polymerase from the DNA (PubMed:11250903, PubMed:11283244, PubMed:16858408, PubMed:34671025, PubMed:34887565, PubMed:36271492). Forms Pol I active center together with the second largest subunit POLR1B/RPA2. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR1A/RPA1 contributing a Mg(2+)-coordinating DxDGD motif, and POLR1B/RPA2 participating in the coordination of a second Mg(2+) ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and the template base. Typically, Mg(2+) ions direct a 5' nucleoside triphosphate to form a phosphodiester bond with the 3' hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate. Has proofreading activity: Pauses and backtracks to allow the cleavage of a missincorporated nucleotide via POLR1H/RPA12. High Pol I processivity is associated with decreased transcription fidelity (By similarity) (PubMed:11250903, PubMed:11283244, PubMed:16858408, PubMed:34671025, PubMed:34887565, PubMed:36271492)

Subcellular location

Nucleus, nucleolusChromosome
Domains and Gene Ontology detail (18)

Gene Ontology

  • Cchromatin
  • Cchromosome
  • Cfibrillar center
  • Cnucleoplasm
  • Cnucleus
  • CRNA polymerase I complex
  • Fchromatin binding
  • FDNA binding
  • FDNA-directed RNA polymerase activity
  • FDNA/RNA hybrid binding
  • Fmagnesium ion binding
  • Fzinc ion binding

1720 aa · 195 kDa

Biological roles

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

Transcriptional regulationUniProt · GO
View supporting evidence

Transcriptional regulation

  • ·Catalytic core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase whi…
  • ·nucleolar large rRNA transcription by RNA polymerase I
  • ·termination of RNA polymerase I transcription
  • ·transcription by RNA polymerase I

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

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.

TAS-106
Narrow target profilePhase 2Inhibitor

DNA-directed RNA polymerase I subunit RPA1 inhibitor

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

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 POLR1A

Gene-level evidence surfaced through the gene POLR1Athat 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.

Benign prostatic hyperplasia
0.42Limited support

Genetic evidence dominant · Open Targets 0.26

Genetic Diseases, Inborn
0.32Limited support

Genetic evidence dominant · Open Targets 0.19

Neurodegenerative Diseases
0.16Preliminary

Pathway evidence dominant · Open Targets 0.23 · no direct causal or clinical evidence

View evidence synthesis (3)
Benign prostatic hyperplasiaLimited support
0.42
agreement 0.300.54
Genetic100%

Open Targets aggregate 0.26 · 1 independent evidence family

Genetic Diseases, InbornLimited support
0.32
agreement 0.200.44
Genetic100%

Open Targets aggregate 0.19 · 1 independent evidence family

Neurodegenerative DiseasesPreliminary
0.16
agreement 0.000.33
Pathway93%Literature7%

Open Targets aggregate 0.23 · 2 independent evidence families · no direct causal or clinical evidence

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
Benign prostatic hyperplasia0.26
Neurodegenerative Diseases0.23
Genetic Diseases, Inborn0.19

Drug development

1 compounds recorded · 1 in clinical development

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: these count different sets and are not a subset relation.

View all recorded compounds (1)
TAS-106Phase 2

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

Advanced Clinical and Structure with Ligand support this modality.

Protein degradersEmerging

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

View underlying tractability evidence (6)
SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

2

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.

ClinicalTrials.gov via the drug-target graph.