POLR2K

Chr 8

RNA 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.

ResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.88
Clinical SummaryPOLR2K
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.88LOEUF
pLI 0.001
Z-score -0.23
OE 1.13 (0.531.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.60Z-score
OE missense 0.70 (0.501.00)
22 obs / 31.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.13 (0.531.88)
00.351.4
Missense OE0.70 (0.501.00)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 4 / 3.5Missense obs/exp: 22 / 31.4Syn Z: -0.21
DN
0.6938th %ile
GOF
0.6053th %ile
LOF
0.51top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found