USP6 Gene (Ubiquitin Specific Peptidase 6)
A key oncogene involved in aneurysmal bone cyst formation and other neoplasms
Gene Information Card
| Symbol | USP6 |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.2 |
| NCBI Gene ID | 9098 ncbi.nlm.nih.gov/gene/9098 |
| Ensembl ID | ENSG00000129204 |
| UniProt ID | P35125 |
| OMIM ID | 604334 |
| HGNC ID | 12612 |
| Aliases | Tre2, TRE17, USP6 (ubiquitin specific peptidase 6) |
Description
USP6 (Ubiquitin Specific Peptidase 6) encodes a deubiquitinating enzyme that removes ubiquitin from target proteins, thereby regulating protein stability and signaling pathways. It is a well-established oncogene, frequently activated by chromosomal rearrangements that lead to its overexpression. USP6 fusions are a hallmark of primary aneurysmal bone cyst (ABC) and nodular fasciitis, and are also found in other benign and malignant neoplasms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Aneurysmal Bone Cyst (ABC) | USP6 gene fusions (e.g., CDH11-USP6) lead to USP6 overexpression, driving osteoclastogenesis and tumor formation. | NCBI Gene, OMIM, ClinVar |
| Nodular Fasciitis | USP6 rearrangements (e.g., MYH9-USP6) cause USP6 overexpression, promoting myofibroblastic proliferation. | NCBI Gene, OMIM, ClinVar |
| Myositis Ossificans | USP6 fusions are identified in a subset of cases, suggesting a similar mechanism to ABC. | NCBI Gene, OMIM |
| Fibroma of Tendon Sheath | USP6 rearrangements have been reported, linking it to benign fibrous tumors. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 0.0 | Not detected |
| Lymph node | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
| Testis | 0.0 | Not detected |
| Thyroid | 0.0 | Not detected |
| Adipose tissue | 0.0 | Not detected |
| Brain | 0.0 | Not detected |
| Heart | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Pancreas | 0.0 | Not detected |
| Prostate | 0.0 | Not detected |
| Skin | 0.0 | Not detected |
| Small intestine | 0.0 | Not detected |
| Stomach | 0.0 | Not detected |
| Colon | 0.0 | Not detected |
| Esophagus | 0.0 | Not detected |
| Ovary | 0.0 | Not detected |
| Breast | 0.0 | Not detected |
| Cervix | 0.0 | Not detected |
| Endometrium | 0.0 | Not detected |
| Fallopian tube | 0.0 | Not detected |
| Vagina | 0.0 | Not detected |
| Placenta | 0.0 | Not detected |
| Adrenal gland | 0.0 | Not detected |
| Pituitary gland | 0.0 | Not detected |
| Salivary gland | 0.0 | Not detected |
| Skeletal muscle | 0.0 | Not detected |
| Smooth muscle | 0.0 | Not detected |
| Tonsil | 0.0 | Not detected |
| Urinary bladder | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 0.0 | Not detected |
| HEK 293 | 0.0 | Not detected |
| K562 | 0.0 | Not detected |
| MCF7 | 0.0 | Not detected |
| A549 | 0.0 | Not detected |
| HepG2 | 0.0 | Not detected |
| SH-SY5Y | 0.0 | Not detected |
| THP-1 | 0.0 | Not detected |
| U2OS | 0.0 | Not detected |
| Jurkat | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CDH11-USP6 fusion | Gene fusion | Common in ABC | Overexpression of USP6, leading to oncogenic signaling |
| MYH9-USP6 fusion | Gene fusion | Common in nodular fasciitis | Overexpression of USP6, promoting myofibroblastic proliferation |
| COL1A1-USP6 fusion | Gene fusion | Rare | Overexpression of USP6 |
| TRAP150-USP6 fusion | Gene fusion | Rare | Overexpression of USP6 |
| USP6 amplification | Copy number gain | Rare | Increased USP6 expression |
Mutation functional classification
Loss of Function (LOF)
Not applicable; USP6 is an oncogene activated by overexpression, not loss-of-function.
Gain of Function (GOF)
USP6 gene fusions and amplifications result in gain-of-function through overexpression of the deubiquitinase, leading to increased cell proliferation and tumorigenesis.
Dominant Negative (DN)
Not reported for USP6.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • cytoplasm (GO:0005737) | • nucleus (GO:0005634) |
| • protein deubiquitination (GO:0016579) | • proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) |
Pathways
• Ubiquitin-proteasome system
• RANKL signaling (osteoclastogenesis)
• MAPK signaling (via USP6-mediated stabilization of signaling intermediates)
Protein Summary
USP6 (Ubiquitin Specific Peptidase 6) is a 1406-amino acid deubiquitinating enzyme that cleaves ubiquitin from target proteins, thereby preventing their proteasomal degradation. It contains an N-terminal Tre2 domain and a C-terminal catalytic USP domain. USP6 is normally expressed at very low levels in most adult tissues, but is highly overexpressed in certain tumors due to promoter swapping from gene fusions. Overexpressed USP6 stabilizes proteins involved in cell growth and osteoclast differentiation, such as MMP9 and NFATc1, contributing to the pathogenesis of aneurysmal bone cyst and nodular fasciitis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP6 Knockout HEK293 Cell Line | EDJ-KQ6459 | Human | 9098 | Details Get a Quote |
| USP6NL Knockout HEK293 Cell Line | EDJ-KQ6709 | Human | 9712 | Details Get a Quote |
| USP6NL Knockout A-549 Cell Line | EDJ-KQ31074 | Human | 9712 | Details Get a Quote |
| USP6NL Knockout HCT 116 Cell Line | EDJ-KQ31075 | Human | 9712 | Details Get a Quote |
| USP6NL Knockout HeLa Cell Line | EDJ-KQ31076 | Human | 9712 | Details Get a Quote |
| USP6 Knockout HeLa Cell Line | EDJ-KQ55085 | Human | 9098 | Details Get a Quote |
| USP6 Knockout A-549 Cell Line | EDJ-KQ63564 | Human | 9098 | Details Get a Quote |
| USP6 Knockout HCT 116 Cell Line | EDJ-KQ72032 | Human | 9098 | Details Get a Quote |
