XPO4: Exportin 4 Gene
A key regulator of nuclear export and tumor suppression
Gene Information Card
| Symbol | XPO4 |
|---|---|
| Full Name | Exportin 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 13q12.11 |
| NCBI Gene ID | 64328 ncbi.nlm.nih.gov/gene/64328 |
| Ensembl ID | ENSG00000132967 |
| UniProt ID | Q9C0E2 |
| OMIM ID | 610755 |
| HGNC ID | 17797 |
| Aliases | KIAA1721, FLJ13147 |
Description
XPO4 (Exportin 4) encodes a member of the importin beta family of nuclear transport receptors. It mediates the nuclear export of specific cargo proteins, including SMAD3 and eIF5A, thereby regulating TGF-beta signaling and translation. XPO4 functions as a tumor suppressor in hepatocellular carcinoma and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Loss of XPO4 expression leads to nuclear accumulation of SMAD3 and enhanced TGF-beta signaling, promoting tumor progression. | PMID: 18413744; COSMIC |
| Colorectal cancer | XPO4 mutations and reduced expression are associated with poor prognosis and metastasis. | PMID: 25485619; COSMIC |
| Prostate cancer | XPO4 downregulation correlates with aggressive disease and androgen receptor signaling. | PMID: 27323851; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 8.2 | Medium |
| Kidney | 6.5 | Medium |
| Testis | 5.1 | Low |
| Lung | 4.8 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 7.9 | Hepatocellular carcinoma cell line |
| HEK293 | 6.3 | Embryonic kidney cells |
| HeLa | 5.4 | Cervical cancer cells |
| A549 | 4.1 | Lung adenocarcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1246C>T (p.Arg416*) | Nonsense | 0.2% in HCC | Loss of function; truncated protein |
| c.1873G>A (p.Gly625Arg) | Missense | 0.1% in colorectal cancer | Impaired cargo binding |
| c.2215_2216del (p.Leu739fs) | Frameshift | 0.05% in prostate cancer | Loss of nuclear export activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg416*, p.Leu739fs) result in truncated or unstable protein, reducing nuclear export of SMAD3 and eIF5A.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in XPO4.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly625Arg) may produce a dominant-negative effect by competing with wild-type XPO4 for cargo binding.
View complete mutation data：
Gene Ontology (GO)
| • nuclear export signal receptor activity (GO:0005049) | • protein import into nucleus (GO:0006606) |
| • nucleocytoplasmic transport (GO:0006913) | • snRNA export from nucleus (GO:0017050) |
| • regulation of protein export from nucleus (GO:0046822) |
Pathways
• Nuclear export of SMAD3 (TGF-beta signaling)
• Nuclear export of eIF5A (translation regulation)
• Importin beta family mediated transport
Protein Summary
Exportin 4 (XPO4) is a 1137-amino acid nuclear transport receptor that recognizes leucine-rich nuclear export signals (NES) in cargo proteins. It forms a ternary complex with RanGTP and cargo to facilitate export through the nuclear pore complex. Key cargos include SMAD3 (mediating TGF-beta signaling) and eIF5A (involved in translation elongation). XPO4 acts as a tumor suppressor; its loss promotes cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| XPO4 Knockout HEK293 Cell Line | EDJ-KQ16164 | Human | 64328 | Details Get a Quote |
| XPO4 Knockout A-549 Cell Line | EDJ-KQ47360 | Human | 64328 | Details Get a Quote |
| XPO4 Knockout HCT 116 Cell Line | EDJ-KQ47361 | Human | 64328 | Details Get a Quote |
| XPO4 Knockout HeLa Cell Line | EDJ-KQ47362 | Human | 64328 | Details Get a Quote |
| Xpo4 Knockout NIH 3T3 Cell Line | EDJ-KZ82 | Mouse | 57258 | Details Get a Quote |
