POLR2C
protein-codingRNA polymerase II subunit C, the group of RNA polymerase subunits
Gene summary
This gene encodes the third largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a cysteine rich region and exists as a heterodimer with another polymerase subunit, POLR2J. These two subunits form a core subassembly unit of the polymerase. A pseudogene has been identified on chromosome 21. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005387
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to POLR2C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032940.3. 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 | 2 | 2 | ||||
| missense | 2 | 23 | 25 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 2 | 27 | 2 | 0 | 31 |
Highest pathogenic variant AF is 0.000025505475
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_116558.1 | 9 | MANE Select | |
| Ensembl | ENSP00000219252.4 | 9 | MANE Select | |
| Ensembl | ENSP00000456367.1 | 3 | Standard | |
| Ensembl | ENSP00000550637.1 | 8 | 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)
- 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
- protein binding
- protein dimerization activity
Cellular Component
- nucleus
- nucleoplasm
- RNA polymerase II, core complex
- cytosol
- microtubule cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000219252
- Coding exons
- 9
- Length
- 9624
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.86 | 97 | 164 | 0.591 | 0.00000920 | 1798 |
| Missense (PolyPhen) | 30 | 56.963 | 0.52666 | 687 | ||
| Synonymous | 1.14 | 55 | 66.8 | 0.823 | 0.00000397 | 512 |
| Loss of Function | 2.40 | 8 | 19.4 | 0.413 | 0.00000114 | 194 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000046 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | 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. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. 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. RPB3 is part of the core element with the central large cleft and the clamp element that moves to open and close the cleft (By similarity). {ECO:0000250, ECO:0000269|PubMed:9852112}.;
Recessive Scores
- pRec
- 0.240
Intolerance Scores
- LoFtool
- 0.311
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 39.95
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.701
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |