POLR2K
Chr 8RNA polymerase II, I and III subunit K
Also known as: ABC10-alpha, RPABC4, RPB10alpha, RPB12, RPB7.0, hRPB7.0, hsRPB10a
The POLR2K protein is a small subunit shared by all three RNA polymerases (I, II, and III) that catalyzes transcription of DNA into various RNA species including mRNA, ribosomal RNA, and transfer RNA. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in early infancy, characterized by severe intellectual disability, refractory seizures, and progressive microcephaly. The gene shows tolerance to loss-of-function variants in the general population, suggesting that biallelic mutations are required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
54 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 36 |
Likely Pathogenic | — | — | — | — | 1 |
VUS | — | — | — | — | 11 |
Likely Benign | — | — | — | — | 0 |
Benign | — | — | — | — | 0 |
| Total | — | 48 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
POLR2K · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →No open access results found
External Resources
Links to major genomics databases and tools