POLR3B
Chr 12ADARRNA polymerase III subunit B
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:20413673, PubMed:33558766). 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 largest subunit POLR3A/RPC1. A single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol III. 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). 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
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Highly missense-constrained (top ~0.1%)
ClinVar Variant Classifications
779 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 7 | 5 | 4 | 0 | 16 |
Likely Pathogenic | 14 | 7 | 5 | 0 | 26 |
VUS | 2 | 259 | 24 | 4 | 289 |
Likely Benign | 0 | 0 | 49 | 71 | 120 |
Benign | 0 | 0 | 5 | 0 | 5 |
Conflicting | — | 8 | |||
| Total | 23 | 271 | 87 | 75 | 464 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
POLR3B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
POLR3B-related neurodevelopmental disorder with or without seizures, ataxia, spasticity, and demyelinating neuropathy
strongPOLR3B-related leukodystrophy, hypomyelinating with or without oligodontia and/or hypogonadotropic hypogonadism
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism
MIM #614381Molecular basis of disorder known
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools