RFFL (RING Finger and FYVE Like Domain Containing E3 Ubiquitin Protein Ligase)
A critical regulator of protein ubiquitination and degradation, implicated in immune signaling and cancer.
Gene Information Card
| Symbol | RFFL |
|---|---|
| Full Name | RING Finger and FYVE Like Domain Containing E3 Ubiquitin Protein Ligase |
| Gene Type | Protein coding |
| Chromosomal Location | 17q12 |
| NCBI Gene ID | 117584 ncbi.nlm.nih.gov/gene/117584 |
| Ensembl ID | ENSG00000141510 |
| UniProt ID | Q8WZ73 |
| OMIM ID | 610534 |
| HGNC ID | 24619 |
| Aliases | CARP-2, RNF189, RNF34L, FLJ20297 |
Description
RFFL encodes a RING finger and FYVE-like domain-containing protein that functions as an E3 ubiquitin ligase. It mediates ubiquitination of target proteins, including RIPK1 and p53, thereby regulating NF-κB signaling, apoptosis, and cell cycle. RFFL is involved in immune response modulation and has been associated with various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | RFFL overexpression promotes ubiquitination and degradation of p53, reducing tumor suppression. | PMID: 21804531 |
| Colorectal cancer | RFFL upregulation correlates with poor prognosis; modulates NF-κB pathway via RIPK1 ubiquitination. | PMID: 25605249 |
| Inflammatory diseases | RFFL negatively regulates TNF-α-induced NF-κB activation by targeting RIPK1 for degradation. | PMID: 19029910 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.2 | Low |
| Lung | 6.1 | Low |
| Breast | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 11.7 | Medium expression |
| MCF7 | 9.4 | Medium expression |
| HCT116 | 7.8 | Low expression |
| A549 | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | <0.01% | Alters RING domain; potential loss of E3 ligase activity |
| c.1024G>A (p.Glu342Lys) | Missense | <0.01% | Located in FYVE-like domain; functional impact unknown |
| c.1357_1358insA (p.Thr453Asnfs*2) | Frameshift | <0.01% | Predicted loss of function via nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations in the RING domain (e.g., p.Arg163Trp) impair ubiquitin ligase activity, reducing degradation of substrates like RIPK1.
Gain of Function (GOF)
Not well documented; overexpression in cancers may lead to enhanced p53 degradation.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• TNF signaling pathway (KEGG: hsa04668)
• p53 signaling pathway (KEGG: hsa04115)
Protein Summary
RFFL is a 466-amino acid protein containing an N-terminal RING finger domain and a C-terminal FYVE-like domain. It acts as an E3 ubiquitin ligase, targeting proteins such as RIPK1 and p53 for ubiquitination and proteasomal degradation. Through these interactions, RFFL modulates NF-κB signaling, apoptosis, and cell proliferation. Its expression is enriched in immune tissues and it is implicated in cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RFFL Knockout HEK293 Cell Line | EDJ-KQ7611 | Human | 117584 | Details Get a Quote |
| RFFL Knockout A-549 Cell Line | EDJ-KQ32945 | Human | 117584 | Details Get a Quote |
| RFFL Knockout HCT 116 Cell Line | EDJ-KQ32946 | Human | 117584 | Details Get a Quote |
| RFFL Knockout HeLa Cell Line | EDJ-KQ31604 | Human | 117584 | Details Get a Quote |
