BRF2
protein-codingBRF2 RNA polymerase III transcription initiation factor subunit
Gene summary
This gene encodes one of the multiple subunits of the RNA polymerase III transcription factor complex required for transcription of genes with promoter elements upstream of the initiation site. The product of this gene, a TFIIB-like factor, is directly recruited to the TATA-box of polymerase III small nuclear RNA gene promoters through its interaction with the TATA-binding protein. [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 ~6.6 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 BRF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018310.4. 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 | 0 | |||||
| missense | 70 | 1 | 71 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 71 | 1 | 0 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060780.2 | 4 | MANE Select | |
| Ensembl | ENSP00000220659.6 | 4 | MANE Select | |
| Ensembl | ENSP00000430107.1 | 4 | Standard | |
| Ensembl | ENSP00000430107.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- RNA Polymerase III Abortive And Retractive Initiation
- RNA Polymerase III Transcription Initiation From Type 3 Promoter
- RNA Polymerase III Transcription Initiation
- RNA Polymerase III Transcription
Biological Process
- DNA-templated transcription, initiation
- regulation of transcription by RNA polymerase III
- cellular response to oxidative stress
- transcription preinitiation complex assembly
- RNA polymerase III preinitiation complex assembly
Molecular Function
- RNA polymerase III type 3 promoter sequence-specific DNA binding
- RNA polymerase III type 3 promoter DNA binding
- transcription factor binding
- metal ion binding
Cellular Component
- transcription factor TFIIIB complex
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000220659
- Coding exons
- 4
- Length
- 6637
- Individuals with no LoFs
- 125627
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 121
- Defined
- 125748
- p
- 0.000481
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0239 | 253 | 252 | 1.00 | 0.0000155 | 2650 |
| Missense (PolyPhen) | 47 | 54.812 | 0.85748 | 555 | ||
| Synonymous | 0.0287 | 108 | 108 | 0.996 | 0.00000641 | 921 |
| Loss of Function | 0.785 | 20 | 24.2 | 0.828 | 0.00000190 | 189 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00080 | 0.00080 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00043 | 0.00043 | rare |
| South Asian | 0.0012 | 0.0012 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites (PubMed:11040218, PubMed:11121026, PubMed:11564744, PubMed:26638071). Contributes to the regulation of gene expression; functions as activator in the absence of oxidative stress (PubMed:26638071). Down-regulates expression of target genes in response to oxidative stress (PubMed:26638071). Overexpression protects cells against apoptosis in response to oxidative stress (PubMed:26638071). {ECO:0000269|PubMed:11040218, ECO:0000269|PubMed:11121026, ECO:0000269|PubMed:11564744, ECO:0000269|PubMed:26638071}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.315
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.65
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |