XPO5 (Exportin 5)
A key mediator of nuclear export of precursor microRNAs and other small RNAs, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | XPO5 |
|---|---|
| Full Name | Exportin 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.1 |
| NCBI Gene ID | 57510 ncbi.nlm.nih.gov/gene/57510 |
| Ensembl ID | ENSG00000124571 |
| UniProt ID | Q9HAV4 |
| OMIM ID | 607845 |
| HGNC ID | 12875 |
| Aliases | EXP5, FLJ10038, KIAA1291 |
Description
XPO5 (Exportin 5) encodes a member of the karyopherin family of nuclear transport receptors. Exportin 5 mediates the RanGTP-dependent nuclear export of precursor microRNAs (pre-miRNAs) and other small double-stranded RNAs (e.g., tRNAs, viral RNAs). By transporting pre-miRNAs from the nucleus to the cytoplasm, XPO5 is essential for microRNA biogenesis and post-transcriptional gene regulation. Mutations and altered expression of XPO5 have been associated with various cancers and DICER1 syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| DICER1 syndrome | Loss-of-function mutations in XPO5 impair pre-miRNA export, reducing mature miRNA levels and disrupting tumor suppressor pathways. | ClinVar; OMIM #607845 |
| Colorectal cancer | Somatic mutations and reduced XPO5 expression lead to global miRNA downregulation, promoting tumorigenesis. | NCBI Gene; COSMIC |
| Breast cancer | XPO5 overexpression correlates with poor prognosis; altered miRNA export affects oncogene and tumor suppressor expression. | UniProt; PubMed studies |
| Lung cancer | XPO5 copy number alterations and mutations contribute to miRNA dysregulation and cancer progression. | COSMIC; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 23.4 | High |
| Thyroid | 18.7 | High |
| Adrenal gland | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Breast | 10.5 | Medium |
| Colon | 9.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 14.2 | High expression |
| A549 (lung carcinoma) | 11.6 | Moderate expression |
| MCF7 (breast carcinoma) | 9.8 | Moderate expression |
| HCT116 (colorectal carcinoma) | 8.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1250G>A (p.Arg417Gln) | Missense | 0.02% (gnomAD) | Reduced pre-miRNA binding affinity; associated with DICER1 syndrome |
| c.1873C>T (p.Arg625*) | Nonsense | <0.01% | Loss of function; truncation of C-terminal RanGTP-binding domain |
| c.2146_2147del (p.Leu716fs) | Frameshift | Somatic (COSMIC) | Loss of nuclear export activity; found in colorectal cancer |
| c.2845A>G (p.Ile949Val) | Missense | 0.1% (gnomAD) | Likely benign; no functional impact reported |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg625*, p.Leu716fs) abolish pre-miRNA export, leading to global miRNA depletion and tumor predisposition.
Gain of Function (GOF)
Not well documented; overexpression in some cancers may enhance export of oncogenic miRNAs.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg417Gln) may interfere with wild-type exportin 5 function, reducing miRNA processing efficiency.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005049 (nuclear export signal receptor activity) | • GO:0005515 (protein binding) |
| • GO:0005634 (nucleus) | • GO:0005737 (cytoplasm) |
| • GO:0006606 (protein import into nucleus) | • GO:0015031 (protein transport) |
| • GO:0016973 (poly(A)+ mRNA export from nucleus) | • GO:0031047 (gene silencing by RNA) |
| • GO:0051028 (mRNA transport) |
Pathways
• MicroRNA biogenesis (R-HSA-203927)
• Nuclear export of pre-miRNAs (R-HSA-203929)
• Gene expression (R-HSA-74160)
• Transport of small RNAs (R-HSA-159230)
Protein Summary
Exportin 5 is a 120 kDa nuclear transport receptor that forms a ternary complex with RanGTP and double-stranded RNA cargo (e.g., pre-miRNAs). It binds the 3' overhang of pre-miRNAs and facilitates their translocation through the nuclear pore complex. In the cytoplasm, GTP hydrolysis releases the cargo. The protein contains an N-terminal Ran-binding domain and a C-terminal cargo-binding domain. Structural studies show that XPO5 recognizes the stem-loop and 3' overhang of pre-miRNAs with high specificity. Dysregulation of XPO5 disrupts miRNA homeostasis and contributes to oncogenesis.
Related Services
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|---|---|---|---|---|
| XPO5 Knockout RPE1 hTERT p53-/- Cell Line | EDC08267 | Human | 57510 | Details Get a Quote |
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