RNF216 Gene - E3 Ubiquitin-Protein Ligase RNF216
Genetic, structural, and clinical insights into RNF216 (Ring Finger Protein 216) and its role in ubiquitination, inflammation, and neurological disorders.
Gene Information Card
| Symbol | RNF216 |
|---|---|
| Full Name | Ring Finger Protein 216 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p22.1 |
| NCBI Gene ID | 54476 ncbi.nlm.nih.gov/gene/54476 |
| Ensembl ID | ENSG00000106366 |
| UniProt ID | Q9Y4L5 |
| OMIM ID | 609948 |
| HGNC ID | 21698 |
| Aliases | UIP58, UbcM4IP, TRIAD3, ZIN |
Description
RNF216 encodes an E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins, regulating their degradation or signaling. It plays a role in immune response, neuronal survival, and synaptic function. Mutations in RNF216 are associated with Gordon Holmes syndrome (cerebellar ataxia and hypogonadism) and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gordon Holmes syndrome | Loss-of-function mutations impair ubiquitin ligase activity, leading to neurodegeneration and hypogonadotropic hypogonadism. | OMIM: 212840; ClinVar; PMID: 24686849 |
| Cerebellar ataxia with hypogonadism | Disrupted ubiquitination of synaptic proteins causes cerebellar degeneration. | OMIM: 609948; PMID: 24686849 |
| Intellectual disability | RNF216 mutations affect neuronal development and synaptic plasticity. | ClinVar; PMID: 24686849 |
| Inflammatory bowel disease (potential) | RNF216 regulates NF-kB signaling; altered activity may contribute to inflammation. | PMID: 16940155 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | High | High expression in Purkinje cells |
| Testis | Medium | Moderate expression |
| Heart | Low | Low expression |
| Liver | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal model |
| HeLa (cervical carcinoma) | Medium | Ubiquitous expression |
| HEK293 (embryonic kidney) | Medium | Common cell line |
| Jurkat (T-cell leukemia) | Low | Immune cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2062C>T (p.Arg688Ter) | Nonsense | Rare | Truncated protein, loss of function |
| c.2314C>T (p.Arg772Ter) | Nonsense | Rare | Truncated protein, loss of function |
| c.1742G>A (p.Trp581Ter) | Nonsense | Rare | Premature stop, loss of function |
| c.2269C>T (p.Arg757Cys) | Missense | Rare | Impaired ligase activity |
| c.2395C>T (p.Arg799Trp) | Missense | Rare | Altered substrate binding |
Mutation functional classification
Loss of Function (LOF)
Most RNF216 mutations are loss-of-function, reducing ubiquitin ligase activity and leading to accumulation of substrates, causing neurodegeneration.
Gain of Function (GOF)
No evidence of gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with dimerization or substrate binding, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • Ubiquitin-protein transferase activity | • Zinc ion binding |
| • Protein ubiquitination | • Ubiquitin-dependent protein catabolic process |
| • Regulation of NF-kB signaling | • Synaptic transmission |
| • Cytoplasm | • Nucleus |
Pathways
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• TNF signaling pathway (KEGG: hsa04668)
• Neurotrophin signaling pathway (KEGG: hsa04722)
Protein Summary
RNF216 is a 1046-amino acid E3 ubiquitin ligase containing a RING finger domain, zinc fingers, and a UBA domain. It ubiquitinates various substrates, including receptor-interacting protein (RIP) and synaptic proteins, targeting them for proteasomal degradation. It regulates NF-kB signaling and is critical for neuronal survival. Mutations cause Gordon Holmes syndrome and related disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF216 Knockout HEK293 Cell Line | EDJ-KQ3795 | Human | 54476 | Details Get a Quote |
| RNF216 Knockout A-549 Cell Line | EDJ-KQ25904 | Human | 54476 | Details Get a Quote |
| RNF216 Knockout HCT 116 Cell Line | EDJ-KQ25905 | Human | 54476 | Details Get a Quote |
| RNF216 Knockout HeLa Cell Line | EDJ-KQ25906 | Human | 54476 | Details Get a Quote |
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