RNF146
Ring Finger Protein 146, a ubiquitin ligase involved in DNA damage response and Wnt signaling
Gene Information Card
| Symbol | RNF146 |
|---|---|
| Full Name | Ring Finger Protein 146 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q22.33 |
| NCBI Gene ID | 81847 ncbi.nlm.nih.gov/gene/81847 |
| Ensembl ID | ENSG00000112210 |
| UniProt ID | Q9NTX7 |
| OMIM ID | 612137 |
| HGNC ID | HGNC:21304 |
| Aliases | dactylidin, FLJ12529, RNF146 |
Description
RNF146 (ring finger protein 146) encodes an E3 ubiquitin ligase that contains a RING finger domain and a WWE domain. It is involved in the ubiquitination of target proteins, playing a role in DNA damage repair, Wnt signaling, and apoptosis. The protein is also known as dactylidin and is implicated in cellular stress responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia (SPG) | Loss-of-function mutations in RNF146 impair ubiquitination of proteins involved in axonal transport, leading to neurodegeneration. | ClinVar, OMIM |
| Colorectal cancer | Overexpression of RNF146 promotes Wnt/β-catenin signaling by ubiquitinating AXIN, contributing to tumorigenesis. | COSMIC, PubMed |
| Breast cancer | RNF146 amplification or overexpression correlates with poor prognosis and enhanced DNA repair. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Colon | 6.1 | Low |
| Breast | 5.4 | Low |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 10.8 | Moderate expression |
| HCT116 | 9.5 | Moderate expression |
| MCF7 | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.497C>T (p.Thr166Met) | Missense | 0.01% | Unknown effect, reported in ClinVar |
| c.1000_1001del (p.Glu334Argfs*5) | Frameshift | Rare | Loss of function, associated with spastic paraplegia |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in RNF146 lead to truncated protein and loss of E3 ligase activity, associated with hereditary spastic paraplegia.
Gain of Function (GOF)
Amplification or overexpression of RNF146 in cancers enhances ubiquitination of AXIN, stabilizing β-catenin and activating Wnt signaling.
Dominant Negative (DN)
Not reported for RNF146.
View complete mutation data：
Gene Ontology (GO)
| • E3 ubiquitin ligase activity | • ubiquitin protein ligase binding |
| • zinc ion binding | • protein ubiquitination |
| • DNA damage response | • Wnt signaling pathway |
| • apoptotic process |
Pathways
• Wnt signaling pathway
• Ubiquitin-mediated proteolysis
• DNA damage repair (ATM/ATR)
Protein Summary
RNF146 is a 366-amino acid E3 ubiquitin ligase with a RING finger domain (residues 50-90) and a WWE domain (residues 200-300). It ubiquitinates target proteins such as AXIN and PARP1, regulating Wnt signaling and DNA repair. The protein is localized to the nucleus and cytoplasm, and its dysfunction is linked to neurodegeneration and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF146 Knockout HEK293 Cell Line | EDJ-KQ9770 | Human | 81847 | Details Get a Quote |
| RNF146 Knockout A-549 Cell Line | EDJ-KQ35393 | Human | 81847 | Details Get a Quote |
| RNF146 Knockout HCT 116 Cell Line | EDJ-KQ36610 | Human | 81847 | Details Get a Quote |
| RNF146 Knockout HeLa Cell Line | EDJ-KQ36611 | Human | 81847 | Details Get a Quote |
