USP46: Ubiquitin Specific Peptidase 46
A deubiquitinating enzyme involved in neurodevelopment, synaptic function, and cancer
Gene Information Card
| Symbol | USP46 |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 46 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q12 |
| NCBI Gene ID | 64854 ncbi.nlm.nih.gov/gene/64854 |
| Ensembl ID | ENSG00000138685 |
| UniProt ID | P62068 |
| OMIM ID | 612345 |
| HGNC ID | 20085 |
| Aliases | USP46, deubiquitinating enzyme 46 |
Description
USP46 (Ubiquitin Specific Peptidase 46) encodes a deubiquitinating enzyme that removes ubiquitin from target proteins, regulating their stability and function. It is involved in neurodevelopment, synaptic plasticity, and cell cycle control. Mutations and altered expression are linked to neurodevelopmental disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with intellectual disability and seizures | Loss-of-function mutations impair deubiquitination of synaptic proteins, disrupting neuronal signaling | ClinVar |
| Autism spectrum disorder | Rare variants in USP46 affect synaptic protein turnover, contributing to ASD risk | ClinVar |
| Breast cancer | Overexpression of USP46 stabilizes oncogenic substrates, promoting tumor growth | COSMIC |
| Colorectal cancer | USP46 upregulation correlates with poor prognosis and increased cell proliferation | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.3 | Medium |
| Lung | 5.1 | Low |
| Liver | 3.2 | Low |
| Kidney | 4.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in embryonic kidney cells |
| SH-SY5Y | 18.7 | High expression in neuroblastoma cells |
| MCF7 | 9.8 | Moderate expression in breast cancer cells |
| HCT116 | 11.4 | Moderate expression in colorectal cancer cells |
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.287C>T (p.Pro96Leu) | Missense | Rare | Reduced deubiquitinase activity |
| c.512G>A (p.Arg171Gln) | Missense | Rare | Impaired substrate binding |
| c.763C>T (p.Arg255*) | Nonsense | Rare | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations reduce or abolish deubiquitinase activity, leading to accumulation of ubiquitinated substrates and disrupted cellular signaling.
Gain of Function (GOF)
Not well characterized; overexpression in cancers may confer gain-of-function by stabilizing oncoproteins.
Dominant Negative (DN)
Not reported for USP46.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type deubiquitinase activity | • ubiquitin-specific protease activity |
| • protein deubiquitination | • synaptic vesicle recycling |
| • cell cycle regulation | • nucleus |
| • cytoplasm |
Pathways
• Ubiquitin-proteasome system
• Deubiquitination
• Synaptic vesicle cycle
Protein Summary
USP46 is a 366-amino acid deubiquitinating enzyme belonging to the ubiquitin-specific protease (USP) family. It contains a conserved catalytic domain that cleaves ubiquitin from target proteins, regulating their stability, localization, and activity. USP46 is highly expressed in the brain and testis, and plays critical roles in synaptic function, neurodevelopment, and cell proliferation. Dysregulation is associated with neurodevelopmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP46 Knockout HEK293 Cell Line | EDJ-KQ16082 | Human | 64854 | Details Get a Quote |
| USP46 Knockout HeLa Cell Line | EDJ-KQ45997 | Human | 64854 | Details Get a Quote |
| USP46 Knockout A-549 Cell Line | EDJ-KQ47218 | Human | 64854 | Details Get a Quote |
| USP46 Knockout HCT 116 Cell Line | EDJ-KQ47219 | Human | 64854 | Details Get a Quote |
| USP46 Knockout HAP1 Cell Line | EDC08028 | Human | 64854 | Details Get a Quote |
