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Protein / target

DNA-directed RNA polymerase III subunit RPC1

Encoded byPOLR3AO14802Homo 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

Genetic Diseases, Inborn

Via encoding gene POLR3A · Genetic evidence · score 0.81

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 III (Pol III), a DNA-dependent RNA polymerase which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates.

View complete UniProt function annotation

Catalytic core component of RNA polymerase III (Pol III), a DNA-dependent RNA polymerase which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates. Synthesizes 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci (PubMed:19609254, PubMed:19631370, PubMed:20413673, PubMed:33335104, PubMed:33558764, PubMed:33558766, PubMed:34675218, PubMed:35637192, PubMed:9331371). Pol III-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol III is recruited to DNA promoters type I, II or III with the help of general transcription factors and other specific initiation factors. 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. Transcription termination involves the release of the RNA transcript and polymerase from the DNA (PubMed:20413673, PubMed:33335104, PubMed:33558764, PubMed:33558766, PubMed:33674783, PubMed:34675218). Forms Pol III active center together with the second largest subunit POLR3B/RPC2. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR3A/RPC1 contributing a Mg(2+)-coordinating DxDGD motif, and POLR3B/RPC2 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 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 (PubMed:19609254, PubMed:20413673, PubMed:33335104, PubMed:33558764, PubMed:33674783, PubMed:34675218, PubMed:9331371). Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as a nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway

Subcellular location

NucleusCytoplasm, cytosol
Domains and Gene Ontology detail (20)

Gene Ontology

  • Ccytoplasm
  • Ccytosol
  • Cmembrane
  • Cnucleoplasm
  • Cnucleus
  • CRNA polymerase III complex
  • Fchromatin binding
  • FDNA binding
  • FDNA-directed RNA polymerase activity
  • FDNA/RNA hybrid binding
  • Fmagnesium ion binding
  • Fzinc ion binding

1390 aa · 156 kDa

Biological roles

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

Transcriptional regulationUniProt · GOImmune signallingUniProt · GO
View supporting evidence

Transcriptional regulation

  • ·Catalytic core component of RNA polymerase III (Pol III), a DNA-dependent RNA polymerase…
  • ·RNA polymerase III complex
  • ·DNA-templated transcription
  • ·termination of RNA polymerase III transcription

Immune signalling

  • ·Catalytic core component of RNA polymerase III (Pol III), a DNA-dependent RNA polymerase…
  • ·innate immune response

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 III subunit RPC1 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 POLR3A

Gene-level evidence surfaced through the gene POLR3Athat 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.

Genetic Diseases, Inborn
0.81Well supported

Genetic evidence dominant · Open Targets 0.50

View evidence synthesis (1)
Genetic Diseases, InbornWell supported
0.81
agreement 0.690.94
Genetic100%

Open Targets aggregate 0.50 · 1 independent evidence family

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
Genetic Diseases, Inborn0.50

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 (4)
SM · Advanced ClinicalSM · Structure with LigandPR · Database UbiquitinationPR · Half-life Data

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.