POLR2B
protein-codingRNA polymerase II subunit B, the group of RNA polymerase subunits
Gene summary
This gene encodes the second largest subunit of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase that catalyzes the transcription of DNA into precursors of mRNA, snRNA and microRNA. This subunit and the largest subunit form opposite sides of the center cleft of Pol II. Deletion of the flap loop region of this subunit results in a decrease in the rate of transcriptional elongation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.4 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 POLR2B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000938.3. 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 | 3 | 1 | 4 | |||
| missense | 1 | 51 | 52 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 1 | 64 | 1 | 0 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000929.1 | 25 | MANE Select | |
| Ensembl | ENSP00000312735.5 | 25 | MANE Select | |
| RefSeq | NP_001290197.1 | 23 | Standard | |
| RefSeq | NP_001290198.1 | 24 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| polr2b | Danio rerio | Structure: head Quality: flat abnormal |
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)
- RNA polymerase - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
- Epstein-Barr virus infection - Homo sapiens (human)
Biological Process
- mRNA splicing, via spliceosome
- transcription-coupled nucleotide-excision repair
- transcription by RNA polymerase II
- transcription initiation from RNA polymerase II promoter
- transcription elongation from RNA polymerase II promoter
Molecular Function
- RNA polymerase II activity
- DNA binding
- chromatin binding
- RNA binding
- DNA-directed 5'-3' RNA polymerase activity
Cellular Component
- nuclear chromosome, telomeric region
- nucleus
- nucleoplasm
- RNA polymerase II, core complex
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381227
- Coding exons
- 25
- Length
- 53447
- Individuals with no LoFs
- 125702
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 125748
- p
- 0.000183
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 6.62 | 182 | 661 | 0.275 | 0.0000354 | 7741 |
| Missense (PolyPhen) | 53 | 321.41 | 0.1649 | 3665 | ||
| Synonymous | 1.01 | 194 | 213 | 0.912 | 0.0000109 | 2174 |
| Loss of Function | 5.76 | 14 | 63.5 | 0.220 | 0.00000342 | 783 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00087 | 0.00086 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.00023 | 0.00023 | 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. Second largest component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB2 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template (By similarity). {ECO:0000250, ECO:0000269|PubMed:9852112}.;
Recessive Scores
- pRec
- 0.493
Intolerance Scores
- RVIS EVS
- -1
- RVIS percentile EVS
- 8.32
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.531
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |