USP9X Gene: Ubiquitin-Specific Peptidase 9 X-Linked
A critical regulator of protein stability and signaling, implicated in neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | USP9X |
|---|---|
| Full Name | Ubiquitin specific peptidase 9 X-linked |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.4 |
| NCBI Gene ID | 8239 ncbi.nlm.nih.gov/gene/8239 |
| Ensembl ID | ENSG00000124486 |
| UniProt ID | Q93008 |
| OMIM ID | 300072 |
| HGNC ID | 12632 |
| Aliases | DFFRX, FAF, MRXS99F, SPG79 |
Description
USP9X encodes a member of the peptidase C19 family, a deubiquitinating enzyme that removes ubiquitin from specific target proteins, thereby regulating their stability, localization, and function. It plays a critical role in multiple cellular processes including cell cycle control, DNA damage response, and neurodevelopment. Mutations in USP9X are associated with X-linked intellectual disability and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability (MRXS99F) | Loss-of-function mutations impair deubiquitination of substrates essential for neuronal development and synaptic function. | ClinVar, OMIM |
| Spastic paraplegia (SPG79) | Missense mutations disrupt USP9X catalytic activity, affecting axonal transport and motor neuron survival. | ClinVar, OMIM |
| Cancer (multiple types) | Altered expression or mutations affect oncogenic pathways (e.g., beta-catenin, TGF-beta) leading to tumor progression. | COSMIC, PubMed |
| Developmental delay and facial dysmorphism | Hemizygous mutations in males cause syndromic intellectual disability with characteristic facial features. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Testis | High | High |
| Kidney | Medium | Medium |
| Liver | Medium | Medium |
| Lung | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | High | Commonly used for functional studies |
| HeLa | Medium | Cancer cell line |
| SH-SY5Y | High | Neuroblastoma cell line |
| MCF7 | Medium | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3478C>T (p.Arg1160Ter) | Nonsense | Rare | Loss of function, associated with intellectual disability |
| c.2056A>G (p.Thr686Ala) | Missense | Rare | Impaired catalytic activity, linked to spastic paraplegia |
| c.4678G>A (p.Asp1560Asn) | Missense | Somatic | Gain of function in cancer, promotes cell proliferation |
| c.1234_1235del (p.Leu412fs) | Frameshift | Rare | Loss of function, developmental delay |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (nonsense, frameshift, splice-site) reduce or abolish deubiquitinase activity, leading to accumulation of ubiquitinated substrates and disrupted signaling pathways, particularly in neurons.
Gain of Function (GOF)
Some missense mutations in cancer may enhance USP9X activity or alter substrate specificity, promoting oncogenic pathways such as Wnt/beta-catenin signaling.
Dominant Negative (DN)
Certain missense mutations may produce a protein that retains binding to substrates but lacks catalytic activity, thereby blocking wild-type USP9X function in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase activity | • ubiquitin-specific protease activity |
| • protein deubiquitination | • regulation of protein stability |
| • neurogenesis | • cell cycle |
Pathways
• Ubiquitin-proteasome system
• TGF-beta signaling pathway
• Wnt signaling pathway
• DNA damage response
Protein Summary
USP9X is a large deubiquitinating enzyme (~290 kDa) that specifically cleaves ubiquitin from target proteins, thereby rescuing them from proteasomal degradation. It contains an N-terminal domain involved in substrate recognition and a C-terminal catalytic domain. USP9X regulates key proteins such as beta-catenin, SMAD4, and ANKRD11, influencing cell fate decisions, neuronal morphogenesis, and tumor suppression. Its activity is tightly regulated by phosphorylation and interaction with adaptor proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP9X Knockout HEK293 Cell Line | EDJ-KQ3503 | Human | 8239 | Details Get a Quote |
| USP9X Knockout A-549 Cell Line | EDJ-KQ25307 | Human | 8239 | Details Get a Quote |
| USP9X Knockout HCT 116 Cell Line | EDJ-KQ25308 | Human | 8239 | Details Get a Quote |
| USP9X Knockout HeLa Cell Line | EDJ-KQ25309 | Human | 8239 | Details Get a Quote |
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