RBX1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the RBX1 (Ring-Box 1) gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | RBX1 |
|---|---|
| Full Name | Ring-Box 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.2 |
| NCBI Gene ID | 9978 ncbi.nlm.nih.gov/gene/9978 |
| Ensembl ID | ENSG00000100320 |
| UniProt ID | P62877 |
| OMIM ID | 603256 |
| HGNC ID | 9928 |
| Aliases | Rbx1, ROC1, RNF75, MGC133081 |
Description
The RBX1 gene encodes ring-box 1, a core component of the SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complex. RBX1 binds to cullin proteins and recruits ubiquitin-conjugating enzymes (E2s), facilitating the transfer of ubiquitin to target substrates. This process marks proteins for proteasomal degradation, thereby regulating cell cycle progression, signal transduction, and transcription. RBX1 is essential for the function of multiple cullin-RING ligases (CRLs) and is involved in diverse cellular processes. Its dysregulation has been linked to various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | RBX1 overexpression enhances CRL activity, promoting degradation of tumor suppressors (e.g., p27, p21) and driving oncogenesis. | COSMIC; multiple studies (e.g., PMID: 23455423) |
| Hepatocellular carcinoma | Elevated RBX1 expression correlates with poor prognosis; promotes cell proliferation via SCF-mediated degradation of p27. | PMID: 23455423; ClinVar |
| Colorectal cancer | RBX1 upregulation contributes to tumor progression by enhancing Wnt/β-catenin signaling. | PMID: 25620004 |
| Fanconi anemia (potential) | RBX1 interacts with FANCL, a component of the Fanconi anemia core complex; mutations may impair DNA repair. | UniProt; OMIM |
| Developmental disorders (rare) | Germline mutations in RBX1 may cause syndromic features, though evidence is limited. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.3 | Medium |
| Lymph node | 10.8 | Medium |
| Spleen | 9.5 | Low |
| Testis | 8.2 | Low |
| Brain (cerebellum) | 7.1 | Low |
| Liver | 6.4 | Low |
| Kidney | 5.9 | Low |
| Heart | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.2 | High expression; used in studies of SCF function |
| HEK293 (embryonic kidney) | 14.8 | High expression; common for recombinant protein studies |
| MCF7 (breast cancer) | 12.5 | Moderate-high; associated with proliferation |
| HepG2 (liver cancer) | 11.3 | Moderate; linked to tumor progression |
| A549 (lung cancer) | 10.1 | Moderate; role in cell cycle regulation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.197A>G (p.Tyr66Cys) | Missense | Rare (<0.01%) | May affect protein stability; clinical significance uncertain |
| c.274C>T (p.Arg92Trp) | Missense | Rare (<0.01%) | Potential impact on cullin binding; reported in ClinVar |
| c.340G>A (p.Glu114Lys) | Missense | Rare (<0.01%) | Unknown effect; not well characterized |
| c.421_422del (p.Leu141fs) | Frameshift | Very rare | Predicted loss of function; may be pathogenic |
| c.500A>G (p.Asn167Ser) | Missense | Rare (<0.01%) | No functional data; likely benign |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in RBX1 are rare and may impair SCF complex assembly, leading to cell cycle arrest or apoptosis. Germline loss-of-function variants are likely deleterious, but few have been reported.
Gain of Function (GOF)
Gain-of-function mutations are not well documented; overexpression of wild-type RBX1 is more common in cancers, enhancing CRL activity and promoting oncogenesis.
Dominant Negative (DN)
Dominant-negative mutations could interfere with cullin binding or E2 recruitment, disrupting multiple CRL pathways. However, no confirmed dominant-negative variants have been characterized.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • protein ubiquitination |
| • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process | • cullin-RING ubiquitin ligase complex |
| • nucleus | • cytoplasm |
| • cell cycle | • DNA damage response |
Pathways
• SCF complex-mediated protein degradation
• Cullin-RING ubiquitin ligase (CRL) pathway
• Cell cycle regulation (G1/S transition)
• p53/TP53 signaling
• Wnt/β-catenin signaling
• NF-κB signaling
Protein Summary
The RBX1 protein (also known as ROC1) is a 108-amino acid RING finger protein that serves as an essential subunit of SCF E3 ubiquitin ligases. It binds to cullin proteins (e.g., CUL1, CUL2, CUL3) via its N-terminal domain and recruits E2 ubiquitin-conjugating enzymes through its RING finger motif. This interaction promotes the transfer of ubiquitin from E2 to substrate proteins, targeting them for proteasomal degradation. RBX1 is critical for the ubiquitination of key cell cycle regulators such as p27 and cyclin E, and its overexpression is observed in several cancers, correlating with poor prognosis. The protein is highly conserved across species and is indispensable for embryonic development in mice.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RBX1 Knockout HEK293T Cell Line | EDJ-KQ78167 | Human | 9978 | Details Get a Quote |
| RBX1 Knockout HCT 116 Cell Line | EDJ-KQ78168 | Human | 9978 | Details Get a Quote |
Displaying Records 1 To 2 Of 2 Records
