POLR2E
protein-codingRNA polymerase II, I and III subunit E, the group of RNA polymerase subunits
Gene summary
This gene encodes the fifth largest subunit 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 and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit. A pseudogene is located on chromosome 11. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to POLR2E variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002695.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 28 | 28 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 1 | 0 | 31 | 2 | 1 | 35 |
Highest pathogenic variant AF is 6.898055e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002686.3 | 7 | MANE Select | |
| Ensembl | ENSP00000478303.1 | 7 | MANE Select | |
| RefSeq | NP_001303252.1 | 5 | Standard | |
| RefSeq | NP_001303253.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyrimidine metabolism - Homo sapiens (human)
- Huntington,s disease - Homo sapiens (human)
- Cytosolic DNA-sensing pathway - Homo sapiens (human)
- RNA polymerase - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
Biological Process
- mRNA splicing, via spliceosome
- transcription-coupled nucleotide-excision repair
- transcription initiation from RNA polymerase I promoter
- termination of RNA polymerase I transcription
- transcription by RNA polymerase II
Molecular Function
- RNA polymerase I activity
- RNA polymerase II activity
- RNA polymerase III activity
- DNA binding
- DNA-directed 5'-3' RNA polymerase activity
Cellular Component
- nucleus
- nucleoplasm
- RNA polymerase II, core complex
- RNA polymerase III complex
- RNA polymerase I complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000215587
- Coding exons
- 7
- Length
- 9005
- Individuals with no LoFs
- 125597
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 56
- Defined
- 125653
- p
- 0.000223
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.353 | 129 | 141 | 0.916 | 0.00000926 | 1364 |
| Missense (PolyPhen) | 43 | 44.117 | 0.97468 | 410 | ||
| Synonymous | -2.31 | 80 | 57.7 | 1.39 | 0.00000393 | 401 |
| Loss of Function | 0.212 | 13 | 13.9 | 0.939 | 7.62e-7 | 142 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0015 | notable |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00015 | 0.00014 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process (By similarity). {ECO:0000250, ECO:0000269|PubMed:9852112}.;
Recessive Scores
- pRec
- 0.322
Intolerance Scores
- LoFtool
- 0.525
- RVIS EVS
- -0.43
- RVIS percentile EVS
- 25.37
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |