RNF217: Ring Finger Protein 217
E3 ubiquitin-protein ligase involved in iron homeostasis and hematological malignancies
Gene Information Card
| Symbol | RNF217 |
|---|---|
| Full Name | Ring Finger Protein 217 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q22.1 |
| NCBI Gene ID | 154215 ncbi.nlm.nih.gov/gene/154215 |
| Ensembl ID | ENSG00000146374 |
| UniProt ID | Q8TC41 |
| OMIM ID | 617897 |
| HGNC ID | 26776 |
| Aliases | C6orf172, FLJ23356, MGC131891 |
Description
RNF217 encodes a RING finger domain-containing E3 ubiquitin-protein ligase. The protein is involved in ubiquitination and degradation of target proteins, playing a role in iron homeostasis by regulating transferrin receptor 1 (TFRC) levels. It is also implicated in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia through chromosomal rearrangements at 6q22.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myelodysplastic syndrome (MDS) | RNF217 is fused to ETV6 via t(6;12)(q22;p13) translocation, generating an ETV6-RNF217 fusion protein that may disrupt normal hematopoiesis | PMID: 27680513 |
| Acute myeloid leukemia (AML) | Same ETV6-RNF217 fusion identified in AML cases, suggesting oncogenic role | PMID: 27680513 |
| Iron-refractory iron deficiency anemia (IRIDA) | RNF217-mediated ubiquitination of TFRC affects iron uptake; dysregulation may contribute to iron metabolism disorders | PMID: 31570887 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.3 | Medium |
| Spleen | 9.8 | Medium |
| Liver | 6.5 | Low |
| Lung | 4.2 | Low |
| Testis | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.7 | Highest expression among blood cancer lines |
| HL-60 (leukemia) | 11.2 | High expression |
| HEK 293 (embryonic kidney) | 5.4 | Moderate expression |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1_? (fusion with ETV6) | Translocation | Rare | Generation of ETV6-RNF217 fusion protein; likely gain-of-function |
| p.Arg123Trp | Missense | <0.01% (gnomAD) | Unknown functional effect; not reported in COSMIC |
| p.Glu287Lys | Missense | <0.01% (gnomAD) | Unknown functional effect; not reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in COSMIC or ClinVar.
Gain of Function (GOF)
ETV6-RNF217 fusion is proposed as a gain-of-function oncogenic event in MDS/AML.
Dominant Negative (DN)
Not described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Iron uptake and transport (Reactome: R-HSA-917937)
Protein Summary
RNF217 is a 456-amino acid E3 ubiquitin-protein ligase containing a RING-type zinc finger domain. It localizes to the cytoplasm and cytosol, where it ubiquitinates target proteins such as transferrin receptor 1 (TFRC), thereby regulating cellular iron uptake. The protein is expressed in hematopoietic tissues and is involved in the pathogenesis of myelodysplastic syndrome and acute myeloid leukemia via fusion with ETV6.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF217 Knockout HEK293 Cell Line | EDJ-KQ11550 | Human | 154214 | Details Get a Quote |
| RNF217 Knockout A-549 Cell Line | EDJ-KQ39883 | Human | 154214 | Details Get a Quote |
| RNF217 Knockout HCT 116 Cell Line | EDJ-KQ39884 | Human | 154214 | Details Get a Quote |
| RNF217 Knockout HeLa Cell Line | EDJ-KQ39885 | Human | 154214 | Details Get a Quote |
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