XPO1

Summary

XPO1 (exportin 1, HGNC:12825) is a protein-coding gene on chromosome 2p15, encoding Exportin-1 (O14980). Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs.

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.

Source: NCBI Gene 7514 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 101 total — 14 pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• MANE Select transcript: NM_003400

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12825
Approved symbol	XPO1
Name	exportin 1
Location	2p15
Locus type	gene with protein product
Status	Approved
Aliases	CRM1, CRM-1, emb
Ensembl gene	ENSG00000082898
Ensembl biotype	protein_coding
OMIM	602559
Entrez	7514

Gene structure

Transcript identifiers

Ensembl transcripts: 89 — 61 protein_coding, 15 retained_intron, 10 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000401558, ENST00000404992, ENST00000406957, ENST00000420673, ENST00000428210, ENST00000443240, ENST00000449444, ENST00000451765, ENST00000460037, ENST00000461407, ENST00000468259, ENST00000469337, ENST00000475744, ENST00000476585, ENST00000481073, ENST00000481214, ENST00000492182, ENST00000495003, ENST00000676553, ENST00000676667, ENST00000676771, ENST00000676778, ENST00000676783, ENST00000676789, ENST00000676889, ENST00000676999, ENST00000677110, ENST00000677150, ENST00000677157, ENST00000677190, ENST00000677239, ENST00000677289, ENST00000677290, ENST00000677417, ENST00000677422, ENST00000677476, ENST00000677556, ENST00000677803, ENST00000677813, ENST00000677814, ENST00000677850, ENST00000677928, ENST00000677933, ENST00000678081, ENST00000678113, ENST00000678172, ENST00000678182, ENST00000678263, ENST00000678360, ENST00000678640, ENST00000678741, ENST00000678790, ENST00000678877, ENST00000679035, ENST00000680228, ENST00000852809, ENST00000852810, ENST00000852811, ENST00000852812, ENST00000852813, ENST00000852814, ENST00000852815, ENST00000852816, ENST00000852817, ENST00000852818, ENST00000852819, ENST00000852820, ENST00000852821, ENST00000933474, ENST00000933475, ENST00000933476, ENST00000933477, ENST00000933478, ENST00000933479, ENST00000933480, ENST00000933481, ENST00000933482, ENST00000933483, ENST00000933484, ENST00000933485, ENST00000933486, ENST00000945827, ENST00000945828, ENST00000945829, ENST00000945830, ENST00000945831, ENST00000945832, ENST00000945833, ENST00000945834

RefSeq mRNA: 2 — MANE Select: NM_003400 NM_001410799, NM_003400

CCDS: CCDS33205, CCDS92765

Canonical transcript exons

ENST00000401558 — 25 exons

Exon	Start	End
ENSE00000757711	61493894	61494091
ENSE00001273429	61526420	61526521
ENSE00001375737	61537562	61538356
ENSE00001562200	61477849	61478966
ENSE00003460316	61501996	61502040
ENSE00003464720	61492567	61492748
ENSE00003473306	61496879	61497007
ENSE00003482598	61498673	61498792
ENSE00003495792	61482380	61482539
ENSE00003496857	61488588	61488771
ENSE00003511604	61533772	61533903
ENSE00003544770	61482957	61483091
ENSE00003556668	61495455	61495613
ENSE00003560760	61485768	61485962
ENSE00003560884	61483937	61484105
ENSE00003562381	61502249	61502310
ENSE00003612401	61481185	61481281
ENSE00003613775	61492035	61492198
ENSE00003631255	61492915	61493053
ENSE00003647000	61499713	61499894
ENSE00003647378	61498865	61498913
ENSE00003670017	61488165	61488271
ENSE00003675145	61492325	61492481
ENSE00003677929	61490642	61490776
ENSE00003787921	61522611	61522683

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.6507 / max 647.3953, expressed in 1824 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28665	34.1333	1815
28667	15.2209	1771
28666	1.6270	849
28661	0.9275	424
28668	0.8569	548
28664	0.5084	245
28658	0.4098	186
28663	0.3960	187
28662	0.2443	98
28660	0.1889	59

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.45	gold quality
ventricular zone	UBERON:0003053	99.22	gold quality
germinal epithelium of ovary	UBERON:0001304	99.21	gold quality
epithelium of nasopharynx	UBERON:0001951	99.10	gold quality
parietal pleura	UBERON:0002400	99.09	gold quality
visceral pleura	UBERON:0002401	99.05	gold quality
pleura	UBERON:0000977	99.03	gold quality
esophagus squamous epithelium	UBERON:0006920	98.67	gold quality
embryo	UBERON:0000922	98.62	gold quality
skin of hip	UBERON:0001554	98.57	gold quality
trabecular bone tissue	UBERON:0002483	98.47	gold quality
palpebral conjunctiva	UBERON:0001812	98.42	gold quality
choroid plexus epithelium	UBERON:0003911	98.42	gold quality
ganglionic eminence	UBERON:0004023	98.33	gold quality
pigmented layer of retina	UBERON:0001782	98.27	gold quality
cauda epididymis	UBERON:0004360	98.26	gold quality
superficial temporal artery	UBERON:0001614	98.24	gold quality
caput epididymis	UBERON:0004358	98.18	gold quality
endometrium	UBERON:0001295	98.14	gold quality
squamous epithelium	UBERON:0006914	98.11	gold quality
right uterine tube	UBERON:0001302	98.09	gold quality
bronchial epithelial cell	CL:0002328	98.08	gold quality
gingival epithelium	UBERON:0001949	98.08	gold quality
adrenal tissue	UBERON:0018303	98.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.92	gold quality
calcaneal tendon	UBERON:0003701	97.87	gold quality
amniotic fluid	UBERON:0000173	97.84	gold quality
corpus epididymis	UBERON:0004359	97.82	gold quality
gingiva	UBERON:0001828	97.80	gold quality
seminal vesicle	UBERON:0000998	97.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.13
E-MTAB-6678	no	7.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, MYC, NFAT5, TP53

miRNA regulators (miRDB)

126 targeting XPO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 40)

• CRM1-dependent function of a cis-acting RNA export element (PMID:11884594)
• The carboxy-terminal region of the human immunodeficiency virus type 1 protein Rev has multiple roles in mediating CRM1-related Rev functions. (PMID:12134013)
• Down-modulation of Sam68 expression caused exclusive nuclear retention and colocalization of both Rev and CRM1. (PMID:12134041)
• Reconstitution of nuclear protein export in isolated nuclear envelopes (PMID:12196506)
• Rev is necessary and probably also sufficient for the accumulation of incompletely spliced HIV RNAs at the nuclear pores while CRM1 is needed for translocation across the nuclear pore complex (PMID:12239324)
• CRM1-dependent nuclear export of Smurf1 is essential for the negative regulation of TGF-beta signaling by Smad7. (PMID:12519765)
• Crm1 has a role in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles (PMID:12861014)
• CRM1 binds to ERK3and promotes the cytoplasmic relocalization of ERK3. Enforced localization of ERK3 in the nucleus or cytoplasm markedly attenuates the ability of the kinase to induce cell cycle arrest in fibroblasts. (PMID:12915405)
• used a series of mutants, which were generated by interchanging residues of CRM1s, to examine the relationship of CRM1 functions (PMID:14612415)
• CRM1 has a role in mediating a nuclear export signal to govern nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase following genotoxic stress (PMID:14617633)
• CRM1 binds to Axin in the presence of RanGTP (PMID:14630927)
• Activation-induced deaminase is actively excluded from the nucleus by an exportin CRM1-dependent pathway. (PMID:15117971)
• CRM1-dependent mRNA export may not be mediated via the adenylate uridylate-rich element. (PMID:15126627)
• Heme regulates gene expression by triggering CRM1-dependent nuclear export of BACH1. (PMID:15175654)
• Data show that an isoform of Staufen2, Stau2(59), is exported from the nucleus by two distinct pathways, one of which is RNA-binding domain 3-mediated and the other of which is CRM1 (exportin 1)-dependent. (PMID:15364930)
• C-terminal sequences direct cyclin D1-CRM1 binding (PMID:15513923)
• CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization (PMID:15556946)
• structural model of human CRM1 based on a combination of X-ray crystallography, homology modeling, and electron microscopy (PMID:15574331)
• PHAX and CRM1 have roles in transporting U3 snoRNA to nucleoli (PMID:15574332)
• Data suggest that CRM1 is able to bind cargo in the nucleolus, and upon RanGTP binding a functional export complex is produced that is exported to the cytoplasm. (PMID:15632073)
• CRM1 regulates active export of Fanconi anemia complementation group A (FANCA)protein out of the nucleus (PMID:15790592)
• Nuclear targeting of adenovirus type 2 requires XPO1-mediated nuclear export. (PMID:15814838)
• Crm1 and Ran-GTP are essential for Ran-BP2/Ran-GAP1 recruitment to kinetochores, for definition of kinetochore fibres and for chromosome segregation at anaphase. Thus, Crm1 is a critical Ran-GTP effector for mitotic spindle assembly and function. (PMID:15908946)
• These data demonstrate that Arg-214/215 are involved in CRM1-mediated STAT3 nuclear export and the regulation of STAT3 activity. (PMID:16140268)
• Review proposes that Ran/Crm1 may act as a ’loading dock’ to coordinate various checkpoint factors in regulating the fidelity of centrosome duplication during cell cycle progression. (PMID:16294017)
• the HuR-CRM1 axis affects the nucleocytoplasmic translocation of CD83 mRNA under regular physiological conditions (PMID:16484227)
• A study evaluting the species-specific barrier of HTLV-1 by establishing rat cell lines, including both adherent and CD4(+) T cells, which express human CRM1 at physiological levels, is reported. (PMID:16504563)
• We found that nuclear export of EGFR may involve CRM1 exportin as we detected EGFR/CRM1 interaction and markedly increased nuclear EGFR following exposure to leptomycin B, a CRM1 inhibitor. (PMID:16552725)
• role of the CRM1-dependent export pathway for the expression of CD83 and other genes under conditions of T cell activation (PMID:16580684)
• the Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60 S preribosomal nuclear export (PMID:16675447)
• Results suggest that decreased expression of exportin-1 and exportin-t induced by 1alpha,25-dihydroxyvitamin D3 can be correlated to inhibition of the proliferation of HL-60 cells. (PMID:16707848)
• The Nup214/Nup88 complex is required for efficient CRM1-mediated transport, supporting a model involving a high-affinity binding site for CRM1 at Nup214 in the terminal steps of export. (PMID:16943420)
• Cellular release of TNFalpha from stimulated leukocytes is mediated by the CRM1-dependent nuclear export mechanism. (PMID:17064665)
• Our report shows the functional significance of the Survivin-Crm1 interface and provides a novel link between the mitotic effector Crm1 and the CPC. (PMID:17099693)
• proof of principle that it is possible to differentially modulate the IFNgamma-induced expression of the HLA-E and HLA-A genes; stimulation of HLA-A expression by IFN-gamma requires nuclear export of HLA-A mRNA by chromosome maintenance region 1 (CRM-1). (PMID:17142760)
• The export receptor CRM1 is a key player in the molecular mechanism for maintaining snRNP trafficking pathways. (PMID:17405816)
• the direct interaction of survivin with the nuclear export receptor Crm1 is critically involved in its intracellular localization and cancer-relevant functions [review] (PMID:17616652)
• CRM1 may down-regulate Cdc7 by masking its kinase domain (PMID:17711849)
• human cytomegalovirus tegument protein pp65 nuclear export requires cyclin-dependent kinase activity and the Crm1 exporter (PMID:17715235)
• Inhibition of exportin-1-mediated nuclear export slowed down nucleocytoplasmic shuttling of v-Src-activated STAT3 resulting in reduced tyrosine phosphorylation, decreased induction of STAT3 target genes and increased apoptosis. (PMID:17726064)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	xpo1b	ENSDARG00000063229
mus_musculus	Xpo1	ENSMUSG00000020290
rattus_norvegicus	Xpo1	ENSRNOG00000009935
drosophila_melanogaster	emb	FBGN0020497
caenorhabditis_elegans		WBGENE00002078

Paralogs (1): XPO5 (ENSG00000124571)

Protein

Protein identifiers

Exportin-1 — O14980 (reviewed: O14980)

Alternative names: Chromosome region maintenance 1 protein homolog

All UniProt accessions (23): O14980, A0A7I2V2C5, A0A7I2V2H0, A0A7I2V2S3, A0A7I2V2Y6, A0A7I2V396, A0A7I2V3J1, A0A7I2V3N0, A0A7I2V3P3, A0A7I2V3W6, A0A7I2V461, A0A7I2V488, A0A7I2V4A3, A0A7I2V531, A0A7I2V6B9, A0A7I2YQP1, A0A7I2YQV4, A0A7I2YQX3, A0A7P0Z4B7, C9IYM2, C9J673, C9JKM9, F8WF71

UniProt curated annotations — full annotation on UniProt →

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. (Microbial infection) Mediates the export of unspliced or incompletely spliced RNAs out of the nucleus from different viruses including HIV-1, HTLV-1 and influenza A. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization.

Subunit / interactions. Found in a U snRNA export complex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. 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. Interacts with HAX1. Interacts with BOK; translocates to the cytoplasm. Interacts with HSP90AB1. 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. (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.

Subcellular location. Cytoplasm. Nucleus. Nucleoplasm. Cajal body. Nucleolus.

Tissue specificity. 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.

Miscellaneous. Cellular target of leptomycin B (LMB), a XPO1/CRM1 nuclear export inhibitor.

Similarity. Belongs to the exportin family.

RefSeq proteins (2): NP_001397728, NP_003391* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001494	Importin-beta_N	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR013598	Exportin-1/Importin-b-like	Domain
IPR014877	XPO1_C_dom	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR040485	XPO1_repeat_3	Repeat
IPR041123	CRM1_repeat	Repeat
IPR041235	Exp1_repeat_2	Repeat
IPR045065	XPO1/5	Family

Pfam: PF03810, PF08389, PF08767, PF18777, PF18784, PF18787

UniProt features (142 total): helix 68, mutagenesis site 25, strand 12, repeat 10, turn 10, modified residue 7, region of interest 5, sequence conflict 3, chain 1, domain 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
1W9C	X-RAY DIFFRACTION	2.3
9OGD	ELECTRON MICROSCOPY	2.49
7B51	X-RAY DIFFRACTION	2.58
9HFL	ELECTRON MICROSCOPY	2.62
5DIS	X-RAY DIFFRACTION	2.85
3GB8	X-RAY DIFFRACTION	2.9
9B62	ELECTRON MICROSCOPY	2.9
9OG9	ELECTRON MICROSCOPY	2.93
6TVO	X-RAY DIFFRACTION	3.2
9OGB	ELECTRON MICROSCOPY	3.25
9OGE	ELECTRON MICROSCOPY	3.28
9OGA	ELECTRON MICROSCOPY	3.37
9OGC	ELECTRON MICROSCOPY	3.37
4BSN	X-RAY DIFFRACTION	4.1
9OGF	ELECTRON MICROSCOPY	4.21
8URJ	ELECTRON MICROSCOPY	4.25
4BSM	X-RAY DIFFRACTION	4.5
2L1L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14980-F1	91.62	0.79

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 391, 446, 448, 450, 454, 693, 1031

Mutagenesis-validated functional residues (25):

Position	Phenotype
191	does not abolish rex-mediated mrna export.
284	does not abolish rex-mediated mrna export.
334	does not abolish rex-mediated mrna export.
337	does not abolish rex-mediated mrna export.
346	does not abolish rex-mediated mrna export.
402	does not abolish rex-mediated mrna export.
411	strongly abolishes interaction with rex and ranbp3, abolishes rex-mediated mrna export. does not abolish interaction wit
412	does not abolish interaction with rex and ranbp3, and rex-mediated mrna export.
414	strongly abolishes interaction with rex and ranbp3, abolishes rex-mediated mrna export. does not abolish interaction wit
428–447	abolishes ran binding activity in absence of cargo and abolishes partially ran binding activity in presence of cargo.
430–446	partially restores ran binding activity in presence of cargo.
430–433	abolishes ran binding activity both in absence or presence of cargo.
454	does not abolish ran binding activity and nuclear export complex formation.
474	strongly abolishes interaction with rex and ranbp3, abolishes rex-mediated mrna export.
481	strongly abolishes interaction with rex and ranbp3, abolishes rex-mediated mrna export.
513	abolishes ran binding activity and nuclear export complex formation. abolishes ran binding activity and nuclear export c
525	enhances ran binding activity and does not abolish nuclear export complex formation. does not abolish ran binding activi
550	enhances ran binding activity and does not abolish nuclear export complex formation; when associated with a-553 and a-59
553	enhances ran binding activity and does not abolish nuclear export complex formation; when associated with a-550 and a-59
554	partially abolishes ran binding activity and does not abolish nuclear export complex formation. abolishes ran binding ac
561	abolishes ran binding activity and nuclear export complex formation. abolishes ran binding activity and nuclear export c
568	does not abolish ran binding activity and partially abolish nuclear export complex formation; when associated with a-525
572	does not abolish ran binding activity and partially abolish nuclear export complex formation; when associated with a-525
583	enhances ran binding activity; when associated with a-590.
590	enhances ran binding activity and does not abolish nuclear export complex formation. enhances ran binding activity and d

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-165054	Rev-mediated nuclear export of HIV RNA
R-HSA-168333	NEP/NS2 Interacts with the Cellular Export Machinery
R-HSA-2173788	Downregulation of TGF-beta receptor signaling
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-450520	HuR (ELAVL1) binds and stabilizes mRNA
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-68877	Mitotic Prometaphase
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-9707616	Heme signaling
R-HSA-9768919	NPAS4 regulates expression of target genes
R-HSA-9828806	Maturation of hRSV A proteins
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-9918432	Maturation of DENV proteins

MSigDB gene sets: 768 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, PID_HDAC_CLASSI_PATHWAY, MORF_DNMT1, GOBP_RIBOSOME_BIOGENESIS, GOBP_NEURON_RECOGNITION, WANG_CLIM2_TARGETS_UP, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, MORF_SMC1L1, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, PAX4_01, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GGGNRMNNYCAT_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (19): ribosomal subunit export from nucleus (GO:0000054), ribosomal large subunit export from nucleus (GO:0000055), ribosomal small subunit export from nucleus (GO:0000056), negative regulation of transcription by RNA polymerase II (GO:0000122), mRNA export from nucleus (GO:0006406), protein export from nucleus (GO:0006611), nucleocytoplasmic transport (GO:0006913), response to xenobiotic stimulus (GO:0009410), regulation of centrosome duplication (GO:0010824), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), protein localization to nucleus (GO:0034504), ribosome biogenesis (GO:0042254), regulation of protein export from nucleus (GO:0046825), cellular response to triglyceride (GO:0071401), cellular response to salt (GO:1902075), intracellular protein transport (GO:0006886), protein transport (GO:0015031), regulation of protein catabolic process (GO:0042176), mRNA transport (GO:0051028)

GO Molecular Function (6): RNA binding (GO:0003723), nuclear export signal receptor activity (GO:0005049), protein domain specific binding (GO:0019904), small GTPase binding (GO:0031267), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (13): kinetochore (GO:0000776), nucleus (GO:0005634), nuclear envelope (GO:0005635), annulate lamellae (GO:0005642), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), Cajal body (GO:0015030), membrane (GO:0016020), nuclear membrane (GO:0031965), protein-containing complex (GO:0032991), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Late Phase of HIV Life Cycle	1
Interactions of Rev with host cellular proteins	1
Export of Viral Ribonucleoproteins from Nucleus	1
TGF-beta receptor signaling activates SMADs	1
Mitotic Anaphase	1
TCF dependent signaling in response to WNT	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1
RHO GTPase Effectors	1
MAPK family signaling cascades	1
M Phase	1
G2/M Transition	1
Extra-nuclear estrogen signaling	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nuclear export	3
ribosomal subunit export from nucleus	2
intracellular protein localization	2
intracellular membraneless organelle	2
nucleus	2
nuclear lumen	2
ribosome localization	1
ribosome biogenesis	1
establishment of organelle localization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
intracellular protein transport	1
nuclear transport	1
response to chemical	1
regulation of centrosome cycle	1
centrosome duplication	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
regulation of proteasomal protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
protein localization to organelle	1
ribonucleoprotein complex biogenesis	1
protein export from nucleus	1
regulation of intracellular protein transport	1
regulation of nucleocytoplasmic transport	1
response to triglyceride	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
cellular response to chemical stimulus	1
response to salt	1
protein transport	1
intracellular transport	1
transport	1
establishment of protein localization	1
regulation of catabolic process	1
protein catabolic process	1

Protein interactions and networks

STRING

5454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XPO1	SNUPN	O95149	994
XPO1	DDX3X	O00571	992
XPO1	NUP214	P35658	991
XPO1	NMD3	Q96D46	990
XPO1	PHAX	Q9H814	987
XPO1	RAN	P17080	975
XPO1	RANBP2	P49792	965
XPO1	NUP88	Q99567	956
XPO1	CSE1L	P55060	939
XPO1	RANGAP1	P46060	936
XPO1	XPOT	O43592	929
XPO1	NXF3	Q9H4D5	922
XPO1	LRPPRC	P42704	921
XPO1	NCBP1	Q09161	905
XPO1	XPO4	Q9C0E2	894

IntAct

303 interactions, top by confidence:

A	B	Type	Score
XPO1	SNUPN	psi-mi:“MI:0915”(physical association)	0.820
XPO1	SNUPN	psi-mi:“MI:0407”(direct interaction)	0.820
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
XPO1	rev	psi-mi:“MI:0915”(physical association)	0.610
XPO1	rev	psi-mi:“MI:0407”(direct interaction)	0.610
XPO1	TP53	psi-mi:“MI:0915”(physical association)	0.590
ERBB2	XPO1	psi-mi:“MI:0915”(physical association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530

BioGRID (1825): XPO1 (Affinity Capture-MS), ABL1 (Protein-peptide), XPO1 (Affinity Capture-Western), PPARG (Affinity Capture-Western), RAN (Affinity Capture-Western), XPO1 (Affinity Capture-RNA), XPO1 (Affinity Capture-MS), XPO1 (Affinity Capture-MS), XPO1 (Affinity Capture-MS), XPO1 (Affinity Capture-MS), XPO1 (Two-hybrid), XPO1 (Affinity Capture-RNA), ANXA5 (Co-fractionation), BASP1 (Co-fractionation), CAD (Co-fractionation)

ESM2 similar proteins: A0JN27, C9WPN6, F1LTR1, F1QGW6, O14787, O14980, O15294, P17427, P18484, P20461, P41091, P52296, P52297, P56558, P61201, P61202, P61203, P70168, P81436, P81795, Q13888, Q14974, Q27HV0, Q28D01, Q2KHU8, Q2TBV5, Q2VIR3, Q3SYU7, Q5F398, Q5HZM6, Q5R797, Q5RIC0, Q5SP67, Q5ZHS1, Q5ZMS3, Q6IQT4, Q6IR75, Q6NVL5, Q6P1K8, Q6P5F9

Diamond homologs: F4IZR5, O14980, P14068, P30822, Q54EV7, Q6P5F9, Q80U96, Q9SMV6, Q9TVM2

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
XPO1	“down-regulates activity”	TP53	relocalization
Verdinexor	down-regulates	XPO1	“chemical inhibition”
Selinexor	“down-regulates activity”	XPO1	“chemical inhibition”
STK38	“up-regulates activity”	XPO1	phosphorylation
XPO1	down-regulates	SMAD4	relocalization
RAN	“up-regulates activity”	XPO1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 193 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signal transduction by L1	5	21.8×	1e-03
FCERI mediated MAPK activation	5	14.5×	4e-03
MAPK6/MAPK4 signaling	8	9.1×	1e-03
PIP3 activates AKT signaling	10	5.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance	5	16.7×	6e-03
learning or memory	6	9.4×	9e-03
protein import into nucleus	10	9.4×	2e-04
protein phosphorylation	11	4.9×	6e-03
DNA damage response	12	4.2×	8e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — CLLSLL, DLBCLNOS, NHL.

Clinical variants and AI predictions

ClinVar

101 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	0
Uncertain significance	37
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
4073394	NM_003400.4(XPO1):c.315C>G (p.Tyr105Ter)	Pathogenic
4073396	NM_003400.4(XPO1):c.1343C>A (p.Thr448Lys)	Pathogenic
4073397	NM_003400.4(XPO1):c.1361A>G (p.Tyr454Cys)	Pathogenic
4073399	NM_003400.4(XPO1):c.1575A>C (p.Leu525Phe)	Pathogenic
4073401	NM_003400.4(XPO1):c.1704G>T (p.Lys568Asn)	Pathogenic
4073402	NM_003400.4(XPO1):c.1949A>C (p.Gln650Pro)	Pathogenic
4073403	NM_003400.4(XPO1):c.2146G>T (p.Asp716Tyr)	Pathogenic
4073404	NM_003400.4(XPO1):c.2150T>G (p.Met717Arg)	Pathogenic
4073405	NM_003400.4(XPO1):c.553C>T (p.Gln185Ter)	Pathogenic
4073409	NM_003400.4(XPO1):c.888+1G>A	Pathogenic
4073410	NM_003400.4(XPO1):c.1282del (p.Glu428fs)	Pathogenic
4073411	NM_003400.4(XPO1):c.1887+1G>T	Pathogenic
4073412	NM_003400.4(XPO1):c.2022+886_2314-728del	Pathogenic
4073413	NM_003400.4(XPO1):c.2293C>T (p.Arg765Ter)	Pathogenic

SpliceAI

5110 predictions. Top by Δscore:

Variant	Effect	Δscore
2:61478962:AATTC:A	acceptor_gain	1.0000
2:61478963:ATTC:A	acceptor_gain	1.0000
2:61478964:TTC:T	acceptor_gain	1.0000
2:61478965:TC:T	acceptor_gain	1.0000
2:61478966:CC:C	acceptor_gain	1.0000
2:61478967:C:CA	acceptor_loss	1.0000
2:61478967:C:CC	acceptor_gain	1.0000
2:61481180:CATA:C	donor_loss	1.0000
2:61481181:ATAC:A	donor_loss	1.0000
2:61481182:TA:T	donor_loss	1.0000
2:61481183:A:AC	donor_gain	1.0000
2:61481184:C:CC	donor_gain	1.0000
2:61481277:GAGCA:G	acceptor_gain	1.0000
2:61481279:GCA:G	acceptor_gain	1.0000
2:61481280:CA:C	acceptor_gain	1.0000
2:61481280:CAC:C	acceptor_gain	1.0000
2:61481282:C:CC	acceptor_gain	1.0000
2:61481283:T:G	acceptor_loss	1.0000
2:61482379:CT:C	donor_gain	1.0000
2:61482423:ATT:A	donor_gain	1.0000
2:61482425:T:TA	donor_gain	1.0000
2:61485845:A:C	donor_gain	1.0000
2:61485872:TAAG:T	donor_gain	1.0000
2:61485880:T:TA	donor_gain	1.0000
2:61485961:ACC:A	acceptor_loss	1.0000
2:61485962:CCTGT:C	acceptor_loss	1.0000
2:61485964:T:C	acceptor_loss	1.0000
2:61488159:ACTT:A	donor_loss	1.0000
2:61488161:TTA:T	donor_loss	1.0000
2:61488163:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000045662 (2:61510488 A>G), RS1000062625 (2:61479911 C>CTGG), RS1000095389 (2:61522411 C>A,T), RS1000122059 (2:61484231 G>A,T), RS1000139164 (2:61495235 A>T), RS1000143356 (2:61480195 A>C,T), RS1000146077 (2:61522183 C>A,T), RS1000177323 (2:61490450 C>T), RS1000187196 (2:61536559 T>C), RS1000221675 (2:61528287 A>G), RS1000249670 (2:61501283 G>A), RS1000250662 (2:61490293 G>C), RS1000328371 (2:61511387 A>G), RS1000329001 (2:61532711 T>G), RS1000401835 (2:61496340 T>C)

Disease associations

OMIM: gene MIM:602559 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): neurodevelopmental disorder (MONDO:0700092), primary amenorrhea (MONDO:1060208)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004606_58	Eosinophil count	3.000000e-10
GCST004624_64	Sum eosinophil basophil counts	5.000000e-10
GCST005752_4	Systemic lupus erythematosus	1.000000e-06
GCST006061_164	Atrial fibrillation	2.000000e-09
GCST006061_33	Atrial fibrillation	2.000000e-11
GCST006956_8	Erectile dysfunction	8.000000e-06
GCST008647_29	Urinary sodium excretion	2.000000e-10
GCST90002381_28	Eosinophil count	2.000000e-15
GCST90002393_188	Monocyte count	7.000000e-13
GCST90002396_208	Mean reticulocyte volume	6.000000e-29
GCST90002398_337	Neutrophil count	2.000000e-19
GCST90002407_223	White blood cell count	1.000000e-25

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0009282	sodium measurement
EFO:0005091	monocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5661 (SINGLE PROTEIN), CHEMBL6195546 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,337 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3545185	SELINEXOR	4	1,675
CHEMBL603	ZAFIRLUKAST	4	23,220
CHEMBL3545187	VERDINEXOR	2	349
CHEMBL129857	AS-602868	1	93

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11125883	Toxicity	3	isoniazid	Drug-induced liver injury;Toxic liver disease
rs4430924	Toxicity	3	Drugs For Treatment Of Tuberculosis	Drug Toxicity;Tuberculosis

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11125883	XPO1	3	0.75	1	isoniazid
rs1050567	XPO1		0.00	0
rs17009924	XPO1		0.00	0
rs12612982	XPO1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Nuclear export proteins

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
selinexor	Inhibition	7.92	pEC50
verdinexor	Inhibition	7.62	pEC50

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5568605	EC50	7 nM
CHEMBL5560534	EC50	19 nM
Verdinexor	EC50	24 nM

ChEMBL bioactivities

153 potent at pChembl≥5 of 161 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	LEPTOMYCIN B
9.00	EC50	1	nM	CHEMBL6190383
8.82	EC50	1.5	nM	CHEMBL6190154
8.70	EC50	2	nM	AS-602868
8.70	EC50	2	nM	CHEMBL6193060
8.60	EC50	2.5	nM	CHEMBL6191562
8.40	EC50	4	nM	CHEMBL5556912
8.40	EC50	4	nM	CHEMBL5555068
8.40	EC50	4	nM	CHEMBL5559223
8.33	EC50	4.7	nM	CHEMBL6193273
8.30	EC50	5	nM	CHEMBL3898452
8.28	EC50	5.3	nM	CHEMBL6193148
8.23	EC50	5.9	nM	AS-602868
8.22	EC50	6	nM	CHEMBL5555068
8.15	EC50	7	nM	CHEMBL5568605
8.15	EC50	7.1	nM	CHEMBL6191512
8.14	EC50	7.3	nM	CHEMBL6192152
8.08	EC50	8.3	nM	CHEMBL6190954
8.05	EC50	9	nM	CHEMBL6190228
8.03	EC50	9.4	nM	CHEMBL6192172
8.01	EC50	9.7	nM	CHEMBL6193465
8.00	IC50	10	nM	CHEMBL4088268
7.96	EC50	11	nM	CHEMBL5542885
7.96	EC50	11	nM	CHEMBL6190907
7.96	EC50	11	nM	CHEMBL6192106
7.92	EC50	12	nM	SELINEXOR
7.92	EC50	12	nM	CHEMBL6191853
7.89	EC50	13	nM	CHEMBL5566091
7.89	EC50	13	nM	CHEMBL6189754
7.80	IC50	16	nM	CHEMBL3898452
7.75	EC50	18	nM	CHEMBL6191728
7.73	Kd	18.74	nM	SELINEXOR
7.72	EC50	19	nM	CHEMBL5560534
7.69	EC50	20.4	nM	CHEMBL6193008
7.68	EC50	21	nM	CHEMBL5564554
7.64	EC50	23	nM	CHEMBL5563530
7.64	EC50	23	nM	CHEMBL6191609
7.62	Kd	24	nM	CHEMBL5093328
7.62	EC50	24	nM	VERDINEXOR
7.62	EC50	24	nM	CHEMBL5562376
7.60	IC50	25	nM	CHEMBL4077955
7.60	EC50	25	nM	CHEMBL5542505
7.60	EC50	25	nM	CHEMBL6193449
7.58	EC50	26	nM	CHEMBL5542934
7.57	Kd	26.95	nM	CHEMBL4440028
7.54	EC50	29.1	nM	CHEMBL6192966
7.52	EC50	30.1	nM	CHEMBL6188931
7.51	EC50	31	nM	CHEMBL6193567
7.47	IC50	34	nM	SELINEXOR
7.47	EC50	34	nM	CHEMBL6191061

PubChem BioAssay actives

73 with measured affinity, of 489 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2E,5S,6R,7S,9R,10E,12E,15R,16Z,18E)-17-ethyl-6-hydroxy-3,5,7,9,11,15-hexamethyl-19-[(2S,3S)-3-methyl-6-oxo-2,3-dihydropyran-2-yl]-8-oxononadeca-2,10,12,16,18-pentaenoic acid	1469802: Inhibition of CRM1-mediated nucleocytoplasmic transport in human HeLa cells after 90 mins by immunofluorescence assay	ic50	0.0010	uM
1-[(5-methoxy-2-thiophen-2-ylquinazolin-4-yl)amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0020	uM
1-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]amino]-3-cyclopropylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0040	uM
1-[(8-chloroquinolin-2-yl)amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0040	uM
N-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]-N-(3-methyl-2,5-dioxopyrrol-1-yl)acetamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0040	uM
propan-2-yl (Z)-3-[3-[3-methoxy-5-(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]prop-2-enoate	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0050	uM
(Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-2-pyrimidin-5-ylprop-2-enamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0070	uM
(2R)-2-[(1E,3Z,5R,7E,9E,11R,13S,14R,15S,17E)-3-ethyl-14-hydroxy-5,9,11,13,15,17-hexamethyl-12-oxononadeca-1,3,7,9,17-pentaenyl]-2,3-dihydropyran-6-one	1469802: Inhibition of CRM1-mediated nucleocytoplasmic transport in human HeLa cells after 90 mins by immunofluorescence assay	ic50	0.0100	uM
1-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]-methylamino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0110	uM
Selinexor	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0120	uM
1-[[6-cyclopropyl-5-(trifluoromethyl)-2-pyridinyl]amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0130	uM
(Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-N-(3,3-difluorocyclobutyl)prop-2-enamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0190	uM
1-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0210	uM
1-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]amino]-3-propan-2-ylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0230	uM
N-[(E)-3-[3,5-bis(trifluoromethyl)phenyl]sulfinylprop-2-enyl]-3-methylbutan-1-amine	1814213: Binding affinity to Cy3 dye-labelled human CRM1 assessed as dissociation constant in absence of RanGTP at 10 uM incubated for 1 hr by micro-scale thermophoresis analysis	kd	0.0240	uM
1-[[8-fluoro-2-(trifluoromethyl)quinazolin-4-yl]amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0240	uM
Verdinexor	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0240	uM
(2S,3S)-2-[(1E,3Z)-3-ethyl-5-methylhexa-1,3-dienyl]-3-methyl-2,3-dihydropyran-6-one	1469802: Inhibition of CRM1-mediated nucleocytoplasmic transport in human HeLa cells after 90 mins by immunofluorescence assay	ic50	0.0250	uM
N-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]-N-(3,4-dimethyl-2,5-dioxopyrrol-1-yl)acetamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0250	uM
1-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]amino]-3-ethylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0260	uM
1-[(S)-[(E)-4-isothiocyanatobut-1-enyl]sulfinyl]-3,5-bis(trifluoromethyl)benzene	1606517: Binding affinity to recombinant His-tagged CRM1 (unknown origin) by SPR analysis	kd	0.0270	uM
1-[[7-cyclopropyl-2-(trifluoromethyl)quinazolin-4-yl]amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0400	uM
3-methyl-1-[(2-thiophen-2-ylquinazolin-4-yl)amino]pyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0480	uM
1-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]amino]-2-hydroxy-2H-pyrrol-5-one	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0550	uM
1-[[5,6-bis(trifluoromethyl)-2-pyridinyl]amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0580	uM
1-[3,5-bis(trifluoromethyl)anilino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0650	uM
3-methyl-1-[[2-(trifluoromethyl)quinazolin-4-yl]amino]pyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0820	uM
3-methyl-1-[[2-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4-yl]amino]pyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0840	uM
3-methyl-1-[[5-(trifluoromethyl)-2-pyridinyl]amino]pyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.0910	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.1060	uM
2-chloro-N-[3-fluoro-5-(trifluoromethyl)phenyl]-4-(trifluoromethyl)pyrimidine-5-carboxamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.1370	uM
3-methyl-1-[[2-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4-yl]amino]pyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.1370	uM
1-[(8-chloroquinolin-2-yl)amino]-3,4-dimethylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.1460	uM
1-[(6-chloro-2-pyridinyl)amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.2060	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149786: Binding affinity to human XPO1 incubated for 45 mins by Kinobead based pull down assay	kd	0.2142	uM
1-[[5-cyclopropyl-2-(trifluoromethyl)quinazolin-4-yl]amino]-3-methylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.2610	uM
methyl (3S,5R,6E,8Z,10R,12E,14E,16R)-3,16-diamino-5-hydroxy-16-[(2S,4S,5S,6S)-4-hydroxy-5-methyl-6-[(E)-prop-1-enyl]oxan-2-yl]-8,10,12-trimethylhexadeca-6,8,12,14-tetraenoate	1971756: Inhibition of CRM1 nuclear export in human HeLa cells assessed as CRM1 depletion measured after 6 hrs	ic50	0.2700	uM
methyl (3S,5R,6E,8Z,10R,12E,14E,16S)-3,16-diamino-5-hydroxy-16-[(2S,4S,5S,6S)-4-hydroxy-5-methyl-6-[(E)-prop-1-enyl]oxan-2-yl]-8,10,12-trimethylhexadeca-6,8,12,14-tetraenoate	1971753: Inhibition of CRM1-mediated nuclear export in human HeLa cells expressing mCherry-tagged NES reporter incubated for 3 hrs by confocal microscopy analysis	ic50	0.3400	uM
1-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]amino]-2-methoxy-2H-pyrrol-5-one	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.3580	uM
1-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]amino]-2H-pyrrol-5-one	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.4040	uM
2-chloro-N-(3,5-difluorophenyl)-4-(trifluoromethyl)pyrimidine-5-carboxamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.5010	uM
2-chloro-N’-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]-N-methylacetohydrazide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.8560	uM
N’-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]prop-2-enehydrazide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	0.9130	uM
1-[(5-methoxy-2-thiophen-2-ylquinazolin-4-yl)amino]pyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	1.3340	uM
1-[3,5-bis(trifluoromethyl)anilino]-3,4-dimethylpyrrole-2,5-dione	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	1.3960	uM
2-chloro-N-phenyl-4-(trifluoromethyl)pyrimidine-5-carboxamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	1.4050	uM
[(E)-4-isothiocyanatobut-1-enyl]sulfinylbenzene	1606516: Inhibition of nuclear CRM1 (unknown origin) by cell based assay	ic50	1.5000	uM
7-methoxy-8-(3-methylbut-2-enyl)chromen-2-one	484914: Inhibition of CRM1-mediated hemagglutininin-tagged HIV1 Rev protein nuclear export in human HeLa cells assessed as nucleus localization after 12 hrs by indirect fluorescent antibody technique	ic50	1.6000	uM
4-[4-[3,5-bis(trifluoromethyl)phenyl]piperazin-1-yl]-3-[(4-bromobenzoyl)amino]benzoic acid	2026023: Binding affinity to CRM1 (unknown origin) assessed as inhibition of CRM1 binding to IAF-conjugated NES PKI by measuring dissociation constant in the presence of RanGTP by competitive MST analysis	kd	1.6000	uM
N-[3,5-bis(trifluoromethyl)phenyl]-6-chloro-2-(trifluoromethyl)pyridine-3-carboxamide	2086224: Inhibition of XPO1 in human Jurkat cells assessed as suppression of IL-2 expression incubated for 6 hrs by Bright-Glo Luciferase based microplate reader analysis	ec50	1.6460	uM

CTD chemical–gene interactions

65 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Valproic Acid	decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
bisphenol A	decreases expression, increases methylation	2
Calcitriol	decreases expression	2
Cannabidiol	increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
tetrachlorobenzoquinone	affects binding, increases reaction	1
GSK-J4	increases expression	1
moringin	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
trichostatin A	affects expression	1
methylparaben	increases expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	decreases expression	1
afimoxifene	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
AICA ribonucleotide	increases reaction, affects binding	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
sulphoraphene	affects binding, decreases expression, affects response to substance	1
piperlongumine	affects binding, decreases activity, decreases reaction, decreases response to substance	1
N-butyrylglucosamine	increases expression	1

ChEMBL screening assays

146 unique, capped per target: 146 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110148	Binding	Inhibition of CRM1-mediated nuclear export of Rio2 in human HeLa cells at 1 uM	The cytotoxic styryl lactone goniothalamin is an inhibitor of nucleocytoplasmic transport. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7VL	Abcam A-549 XPO1 KO	Cancer cell line	Male
CVCL_B7VM	Abcam HCT 116 XPO1 KO	Cancer cell line	Male
CVCL_D1UY	Abcam MCF-7 XPO1 KO	Cancer cell line	Female
CVCL_D5KS	TMD12	Cancer cell line	Male
CVCL_D6JA	SYSUSHi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

203 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice