ZNRF1: Zinc and Ring Finger 1 E3 Ubiquitin Ligase
A key regulator of ubiquitination, neuronal development, and synaptic function
Gene Information Card
| Symbol | ZNRF1 |
|---|---|
| Full Name | Zinc And Ring Finger 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q23.1 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000103197 |
| UniProt ID | Q8ND25 |
| OMIM ID | 612062 |
| HGNC ID | 13127 |
| Aliases | RNF146, ZNF146, FLJ12606 |
Description
ZNRF1 (Zinc And Ring Finger 1) encodes a RING-type E3 ubiquitin ligase that plays a critical role in ubiquitination and proteasomal degradation of target proteins. It is highly expressed in the nervous system and is involved in neuronal development, axon guidance, and synaptic plasticity. ZNRF1 regulates the turnover of key synaptic proteins and has been implicated in neurodevelopmental disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorders | Impaired ubiquitination of synaptic proteins leading to altered neuronal connectivity | PMID: 23452853 |
| Autism spectrum disorder | Dysregulation of ZNRF1 expression affecting synaptic pruning | PMID: 25620204 |
| Schizophrenia | Altered ZNRF1 levels in prefrontal cortex affecting glutamate receptor turnover | PMID: 27089177 |
| Glioblastoma | Overexpression of ZNRF1 promoting tumor cell proliferation via ubiquitination of tumor suppressors | PMID: 28991257 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.2 | Medium |
| Spinal cord | 7.9 | Medium |
| Heart | 3.1 | Low |
| Liver | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
| U87MG (glioblastoma) | 11.8 | High expression |
| HEK293 (embryonic kidney) | 6.4 | Medium expression |
| HeLa (cervical cancer) | 4.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497C>T (p.Thr166Met) | Missense | <0.01% | Reduced E3 ligase activity; associated with neurodevelopmental delay |
| c.832G>A (p.Glu278Lys) | Missense | <0.01% | Altered substrate binding; linked to autism spectrum disorder |
| c.1024_1026del (p.Lys342del) | In-frame deletion | <0.01% | Impaired protein stability; observed in glioblastoma |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Thr166Met) reduce ubiquitin ligase activity, leading to accumulation of synaptic proteins and impaired neuronal development.
Gain of Function (GOF)
Not well characterized; overexpression in glioblastoma may confer gain-of-function by promoting degradation of tumor suppressors.
Dominant Negative (DN)
Not reported for ZNRF1.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • zinc ion binding |
| • protein ubiquitination | • synaptic signaling |
| • nervous system development |
Pathways
• Ubiquitin mediated proteolysis
• Neurotrophin signaling pathway
• Synaptic vesicle cycle
Protein Summary
ZNRF1 is a 366-amino acid protein containing a RING finger domain and a zinc finger domain. It functions as an E3 ubiquitin ligase, catalyzing the transfer of ubiquitin from E2 enzymes to specific substrates, targeting them for proteasomal degradation. In neurons, ZNRF1 regulates the turnover of postsynaptic receptors and scaffolding proteins, thereby modulating synaptic strength and plasticity. Its expression is enriched in brain regions involved in learning and memory. Dysregulation of ZNRF1 has been linked to neurodevelopmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZNRF1 Knockout HEK293 Cell Line | EDJ-KQ10270 | Human | 84937 | Details Get a Quote |
| ZNRF1 Knockout HeLa Cell Line | EDJ-KQ36260 | Human | 84937 | Details Get a Quote |
| ZNRF1 Knockout A-549 Cell Line | EDJ-KQ37506 | Human | 84937 | Details Get a Quote |
| ZNRF1 Knockout HCT 116 Cell Line | EDJ-KQ37507 | Human | 84937 | Details Get a Quote |
