XPO1
protein-codingexportin 1, the group of Exportins
Gene summary
This cell-cycle-regulated gene encodes a protein that mediates leucine-rich nuclear export signal (NES)-dependent protein transport. The protein specifically inhibits the nuclear export of Rev and U snRNAs. It is involved in the control of several cellular processes by controlling the localization of cyclin B, MPAK, and MAPKAP kinase 2. This protein also regulates NFAT and AP-1. [provided by RefSeq, Jan 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to XPO1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003400.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 5 | 3 | 9 | ||
| missense | 8 | 3 | 50 | 1 | 62 | |
| nonsense | 3 | 1 | 3 | 7 | ||
| start loss | 0 | |||||
| frameshift | 2 | 8 | 10 | |||
| splice donor/acceptor (+/-2bp) | 3 | 6 | 9 | |||
| Total | 16 | 4 | 68 | 6 | 3 | 97 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003391.1 | 24 | MANE Select | |
| Ensembl | ENSP00000384863.2 | 24 | MANE Select | |
| RefSeq | NP_001397728.1 | 23 | Standard | |
| Ensembl | ENSP00000385942.2 | 24 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| xpo1a | Danio rerio | Structure: trunk Quality: curved abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Influenza A - Homo sapiens (human)
- Ribosome biogenesis in eukaryotes - Homo sapiens (human)
- HTLV-I infection - Homo sapiens (human)
- RNA transport - Homo sapiens (human)
- Epstein-Barr virus infection - Homo sapiens (human)
Biological Process
- ribosomal subunit export from nucleus
- ribosomal large subunit export from nucleus
- ribosomal small subunit export from nucleus
- negative regulation of transcription by RNA polymerase II
- protein export from nucleus
Molecular Function
- RNA binding
- nuclear export signal receptor activity
- transporter activity
- protein binding
- Ran GTPase binding
Cellular Component
- kinetochore
- nucleus
- nuclear envelope
- annulate lamellae
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000401558
- Coding exons
- 24
- Length
- 60778
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 6.01 | 152 | 548 | 0.277 | 0.0000264 | 7187 |
| Missense (PolyPhen) | 21 | 206.43 | 0.10173 | 2805 | ||
| Synonymous | -1.57 | 211 | 184 | 1.15 | 0.00000922 | 1899 |
| Loss of Function | 7.10 | 0 | 58.7 | 0.00 | 0.00000297 | 721 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap. {ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:20921223, ECO:0000269|PubMed:9311922, ECO:0000269|PubMed:9323133}.;
Recessive Scores
- pRec
- 0.303
Intolerance Scores
- RVIS EVS
- -0.85
- RVIS percentile EVS
- 11.06
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |