POLR2K

Chr 8

RNA polymerase II, I and III subunit K

Also known as: ABC10-alpha, RPABC4, RPB10alpha, RPB12, RPB7.0, hRPB7.0, hsRPB10a

NCBI Gene: 5440 ENSG00000147669 UniProt: P53803 OMIM: 606033

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes one of the smallest subunits of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.88

Clinical Summary— POLR2K

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 4 VUS of 11 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.88LOEUF

pLI 0.001

Z-score -0.23

OE 1.13 (0.53–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.60Z-score

OE missense 0.70 (0.50–1.00)

22 obs / 31.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.13 (0.53–1.88)

0≤0.351.4

Missense OE?0.70 (0.50–1.00)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 4 / 3.5Missense obs/exp: 22 / 31.4Syn Z: -0.21

This gene — mechanism propensity

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

11 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS4

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	0	0
VUS	4	0	4
Likely Benign	0	0	0
Benign	0	0	0
Total	4	1	5

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

37 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap POLR2K — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →