XPO1

exportin 1, the group of Exportins

Basic information

Region (hg38): 2:61476031-61538741

Links

ENSG00000082898 ∙ NCBI:7514 ∙ OMIM:602559 ∙ HGNC:12825 ∙ Uniprot:O14980 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XPO1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XPO1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	3	8
missense			8			8
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					1	1
Total	0	0	9	5	4

Variants in XPO1

This is a list of pathogenic ClinVar variants found in the XPO1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-61478944-G-A		not specified	Uncertain significance (Oct 26, 2021)
2-61481268-G-C		not specified	Uncertain significance (Dec 02, 2021)
2-61482950-T-A			Likely benign (Jul 31, 2018)
2-61484076-C-T			Benign (Dec 31, 2019)
2-61488207-C-T			Likely benign (Apr 01, 2022)
2-61488243-A-C		not specified	Uncertain significance (Jan 23, 2024)
2-61488631-G-A			Benign (Jun 13, 2018)
2-61490712-T-A		Seizure	Uncertain significance (Apr 20, 2023)
2-61492047-A-C			Likely benign (Dec 31, 2019)
2-61492336-T-A		Prostate adenocarcinoma • Breast neoplasm • B-cell chronic lymphocytic leukemia • Malignant neoplasm of body of uterus • Neoplasm of the large intestine	Likely pathogenic (May 31, 2016)
2-61492336-T-G		Malignant neoplasm of body of uterus • Prostate adenocarcinoma • Breast neoplasm • Neoplasm of the large intestine • B-cell chronic lymphocytic leukemia	Likely pathogenic (May 31, 2016)
2-61492337-C-T		Neoplasm of the large intestine • Malignant neoplasm of body of uterus • Prostate adenocarcinoma • Breast neoplasm • B-cell chronic lymphocytic leukemia	Likely pathogenic (May 31, 2016)
2-61492425-T-C			Likely benign (Jun 26, 2018)
2-61492797-T-C		not specified	not provided (Sep 19, 2013)
2-61493980-A-G		not specified	not provided (Sep 19, 2013)
2-61495586-G-A		not specified	Uncertain significance (Oct 02, 2023)
2-61495589-G-A			Uncertain significance (May 04, 2020)
2-61495589-G-T			Benign (Dec 31, 2019)
2-61496870-T-C			Benign (Dec 31, 2019)
2-61498721-G-A			Likely benign (Jun 08, 2018)
2-61498765-G-A		not specified	Uncertain significance (Dec 12, 2023)
2-61499894-T-C		not specified	Uncertain significance (Jun 04, 2024)
2-61502304-T-A		not specified	Uncertain significance (Jan 11, 2023)
2-61526437-G-C		not specified	Uncertain significance (Dec 05, 2022)
2-61526477-A-C			Likely benign (Apr 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XPO1	protein_coding	protein_coding	ENST00000401558	24	60778

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.28e-10	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	6.01	152	548	0.277	0.0000264	7187
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);TGF-Ncore;eIF5A regulation in response to inhibition of the nuclear export system;Disease;Signaling by WNT;Signal Transduction;sonic hedgehog receptor ptc1 regulates cell cycle;Rev-mediated nuclear export of HIV RNA;Late Phase of HIV Life Cycle;HIV Life Cycle;Interactions of Rev with host cellular proteins;Host Interactions of HIV factors;HIV Infection;Export of Viral Ribonucleoproteins from Nucleus;NEP/NS2 Interacts with the Cellular Export Machinery;Influenza Life Cycle;Influenza Infection;Metabolism of RNA;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;Infectious disease;Fibroblast growth factor-1;RHO GTPases Activate Formins;regulation of spermatogenesis by crem;Deactivation of the beta-catenin transactivating complex;Cyclin A/B1/B2 associated events during G2/M transition;RHO GTPase Effectors;Signaling by Rho GTPases;TGF_beta_Receptor;Signaling events mediated by HDAC Class II;HuR (ELAVL1) binds and stabilizes mRNA;G2/M Transition;Mitotic G2-G2/M phases;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Regulation of mRNA stability by proteins that bind AU-rich elements;Resolution of Sister Chromatid Cohesion;Integrin-linked kinase signaling;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Cell Cycle, Mitotic;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs;Canonical NF-kappaB pathway;Regulation of nuclear beta catenin signaling and target gene transcription;TCF dependent signaling in response to WNT;Sumoylation by RanBP2 regulates transcriptional repression;FoxO family signaling;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Signaling events mediated by HDAC Class I;Hedgehog signaling events mediated by Gli proteins (Consensus)

Recessive Scores

• pRec: 0.303

Intolerance Scores

• rvis_EVS: -0.85
• rvis_percentile_EVS: 11.06

Haploinsufficiency Scores

• pHI: 0.997
• hipred: Y
• hipred_score: 0.673
• ghis: 0.668

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Xpo1

Zebrafish Information Network

• Gene name: xpo1a
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• 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;nucleocytoplasmic transport;regulation of centrosome duplication;viral process;protein localization to nucleus;regulation of protein catabolic process;ribosome biogenesis;response to drug;regulation of mRNA stability;regulation of protein export from nucleus;mRNA transport;intracellular transport of virus
• Cellular component: kinetochore;nucleus;nuclear envelope;annulate lamellae;nucleoplasm;nucleolus;cytoplasm;cytosol;Cajal body;membrane;nuclear membrane;protein-containing complex;intracellular membrane-bounded organelle;host cell;ribonucleoprotein complex
• Molecular function: RNA binding;nuclear export signal receptor activity;transporter activity;protein binding;Ran GTPase binding;protein transporter activity;protein domain specific binding