XPO1

Oncogene
Exportin-1 UniProt accession O14980

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

Source: UniProt

Found in a U snRNA export complex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA (By similarity). Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1. Found in a trimeric export complex with SNUPN, RAN and XPO1.

Found in a nuclear export complex with RANBP3 and RAN. Found in a 60S ribosomal subunit export complex with NMD3, RAN, XPO1. Interacts with DDX3X, NMD3, NUP42, NUP88, NUP214, RANBP3 and TERT.

Interacts with NEMF (via its N-terminus). Interacts with the monomeric form of BIRC5/survivin deacetylated at 'Lys-129'. Interacts with DTNBP1 and SERTAD2; the interactions translocate DTNBP1 and SERTAD2 out of the nucleus.

Interacts with ATF2. Interacts with SLC35G1 and STIM1. Interacts with DCAF8.

Interacts with CPEB3 (PubMed:22730302). Interacts with HAX1 (PubMed:23164465). Interacts with BOK; translocates to the cytoplasm (PubMed:16302269).

Interacts with HSP90AB1 (PubMed:22022502). Interacts with LRPPRC; interacts with LRPPRC alone and also when LRPPRC is in complex with EIF4E and with EIF4E sensitivity element (4ESE)-containing mRNAs to form an EIF4E-dependent mRNA export complex (PubMed:28325843)

(Microbial infection) Interacts with HIV-1 Rev

(Microbial infection) Interacts with HTLV-1 Rex

(Microbial infection) Interacts with influenza A nucleoprotein

(Microbial infection) Interacts with Epstein-Barr virus protein BMLF1

(Microbial infection) Part of a tetrameric complex composed of CRM1, importin alpha/beta dimer and the Venezuelan equine encephalitis virus (VEEV) capsid; this complex blocks the receptor-mediated transport through the nuclear pore

(Microbial infection) Interacts with SARS-CoV virus protein ORF9b; this interaction mediates protein ORF9b export out of the nucleus

Source: UniProt
Cytoplasm, Nucleus, nucleoplasm, Nucleus, Cajal body, Nucleus, nucleolus
Source: UniProt

Expressed in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. Not expressed in the kidney

Source: UniProt
  • Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
  • Rev-mediated nuclear export of HIV RNA
  • NEP/NS2 Interacts with the Cellular Export Machinery
  • Downregulation of TGF-beta receptor signaling
  • Separation of Sister Chromatids
  • Resolution of Sister Chromatid Cohesion
  • Deactivation of the beta-catenin transactivating complex
  • HuR (ELAVL1) binds and stabilizes mRNA
  • RHO GTPases Activate Formins
  • MAPK6/MAPK4 signaling
  • Mitotic Prometaphase
  • Cyclin A/B1/B2 associated events during G2/M transition
  • Estrogen-dependent nuclear events downstream of ESR-membrane signaling
  • EML4 and NUDC in mitotic spindle formation
  • Heme signaling
  • NPAS4 regulates expression of target genes
  • Maturation of hRSV A proteins
  • Transcriptional and post-translational regulation of MITF-M expression and activity
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 0.38%
Lung Adenocarcinoma 1.13%
Lung Small Cell Carcinoma 1.19%
Lung Squamous Cell Carcinoma 0.82%
Oesophagus Adenocarcinoma 0.93%
Oesophagus Squamous Cell Carcinoma 0.59%
Pancreas Ductal Carcinoma 0.57%

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to XPO1, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 13

NCT ID Condition Brief Title Phase Status
NCT07523737 Primary Central Nervous System Lymphoma (PCNSL), Diffuse Large B Cell Lymphoma (DLBCL) Pomalidomide, Anti-PD-1 Antibody Combined With Selinexor (PPS) in Relapsed/Refractory Primary Central Nervous System Diffuse Large B-Cell Lymphoma PHASE2 RECRUITING
NCT07554482 Extranodal NK/T-cell Lymphoma Selinexor Combined With Reduced-Dose Radiotherapy For Early-Stage Extranodal NK/T-Cell Lymphoma PHASE2 NOT_YET_RECRUITING
NCT02757586 Leukemia, Lymphocytic, Chronic, B-Cell Treatment of Chronic Lymphocytic Leukemia N/A UNKNOWN
NCT05833893 nk/T-cell Lymphoma, Newly Diagnosed, Advanced Lymphoma Clinical Study of XPO1 Inhibitor Selinexor Combined With COPL in Newly Diagnosed Advanced NK/T-cell Lymphoma PHASE2 RECRUITING
NCT02323880 Malignant Glioma, Recurrent Brain Neoplasm, Recurrent Childhood Central Nervous System Neoplasm, Recurrent Childhood Glioblastoma, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Primary Central Nervous System Neoplasm, WHO Grade 3 Glioma Selinexor in Treating Younger Patients With Recurrent or Refractory Solid Tumors or High-Grade Gliomas PHASE1 COMPLETED
NCT05983276 Ovarian Cancer Decitabine and Selinexor in Combination to Reverse Drug Resistance With Standard Chemotherapy in Ovarian Cancer PHASE2 RECRUITING
NCT05322330 Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma Clinical Study of XPO-1 Inhibitors Plus CAR-T Cells in Relapsed Refractory B-cell Non-Hodgkin's Lymphoma PHASE2 UNKNOWN
NCT02667873 Solid Tumors A Trial of a Novel XPO1 Inhibitor in Participants With Advanced Solid Tumors PHASE1 COMPLETED
NCT02815137 Classical Hodgkin Lymphoma Detection and Prognostic Value of Recurrent XPO1 Mutations of Patients With Classical Hodgkin Lymphoma NA COMPLETED
NCT03095612 Non-small Cell Lung Cancer Phase 1/2 Trial of Selinexor (KPT-330) With Docetaxel for Non-small Cell Lung Cancer (NSCLC) PHASE1, PHASE2 TERMINATED