BRF1 Gene (BRF1, RNA Polymerase III Transcription Initiation Factor Subunit)
Essential regulator of RNA polymerase III-mediated transcription and tRNA synthesis
Gene Information Card
| Symbol | BRF1 |
|---|---|
| Full Name | BRF1, RNA Polymerase III Transcription Initiation Factor Subunit |
| Gene Type | Protein-coding |
| Chromosomal Location | 14q32.33 |
| NCBI Gene ID | 2972 ncbi.nlm.nih.gov/gene/2972 |
| Ensembl ID | ENSG00000100811 |
| UniProt ID | Q92994 |
| OMIM ID | 604902 |
| HGNC ID | 1105 |
| Aliases | TFIIIB90, BRF, hBRF, TF3B90, TFC5 |
Description
The BRF1 gene encodes the 90 kDa subunit of the RNA polymerase III transcription initiation factor TFIIIB. This protein is essential for the initiation of transcription by RNA polymerase III, which synthesizes small non-coding RNAs such as tRNAs, 5S rRNA, and U6 snRNA. BRF1 directly binds to the TATA-binding protein (TBP) and recruits RNA polymerase III to target gene promoters. Mutations in BRF1 are associated with neurodevelopmental disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cerebellar ataxia, intellectual disability, and leukodystrophy | Loss-of-function mutations impair RNA polymerase III transcription, leading to reduced tRNA and 5S rRNA levels, affecting neuronal development and myelination. | ClinVar, OMIM |
| Colorectal cancer | Somatic mutations and altered expression of BRF1 contribute to dysregulated RNA polymerase III activity, promoting cell proliferation. | COSMIC, NCBI |
| Breast cancer | Overexpression of BRF1 enhances Pol III transcription, supporting tumor growth and survival. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.7 | Low |
| Kidney | 9.1 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.8 | Cervical cancer cell line |
| HEK293 | 11.3 | Embryonic kidney cell line |
| K562 | 9.5 | Leukemia cell line |
| HepG2 | 7.2 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Trp) | Missense | Rare | Reduced TFIIIB complex stability and Pol III transcription activity |
| c.1246G>A (p.Gly416Arg) | Missense | Rare | Impaired interaction with TBP, leading to decreased transcription |
| c.1489_1490del (p.Leu497fs) | Frameshift | Rare | Loss of function, associated with cerebellar ataxia |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that reduce or abolish BRF1 protein function, impairing RNA polymerase III transcription and causing neurodevelopmental disorders.
Gain of Function (GOF)
Not well documented; overexpression in cancers may confer a gain-of-function by increasing Pol III transcription.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by disrupting TFIIIB complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • RNA polymerase III transcription initiation | • DNA-binding |
| • transcription initiation factor activity | • protein binding |
| • nucleus |
Pathways
• RNA polymerase III transcription initiation
• tRNA transcription
• 5S rRNA transcription
Protein Summary
BRF1 is a 90 kDa protein that forms the TFIIIB complex with TBP and BDP1. It directly binds to the TATA box via TBP and recruits RNA polymerase III to promoters of genes encoding tRNAs, 5S rRNA, and other small RNAs. The protein contains a conserved N-terminal domain that interacts with TBP and a C-terminal domain that binds RNA polymerase III. BRF1 is essential for cell growth and differentiation.
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