XPO5

Chr 6

exportin 5

Also known as: exp5

NCBI Gene: 57510ENSG00000124571UniProt: Q9HAV4

This gene encodes a member of the karyopherin family that is required for the transport of small RNAs and double-stranded RNA-binding proteins from the nucleus to the cytoplasm. The encoded protein translocates cargo through the nuclear pore complex in a RanGTP-dependent process. [provided by RefSeq, Aug 2011]

340
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— XPO5
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 118 VUS of 340 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.25LOEUF
pLI 1.000
Z-score 6.65
OE 0.15 (0.10–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.11Z-score
OE missense 0.66 (0.60–0.71)
422 obs / 644.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.10–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.60–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 11 / 71.8Missense obs/exp: 422 / 644.2Syn Z: -0.63

ClinVar Variant Classifications

340 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
VUS118
Likely Benign131
Benign80
Conflicting2
9
Pathogenic
118
VUS
131
Likely Benign
80
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
0
0
0
VUS
1
102
13
2
118
Likely Benign
0
8
76
47
131
Benign
0
3
71
6
80
Conflicting
—2
Total111316955340

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

XPO5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — XPO5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association between XPO5 rs11077 polymorphism and cancer susceptibility: a meta-analysis of 7284 cases and 8511 controls.
Moazeni-Roodi A et al.·Exp Oncol
2019Meta-analysis
Microsatellite instability: an update.
Yamamoto H et al.·Arch Toxicol
2015Review
Exportin-5 SUMOylation promotes hepatocellular carcinoma progression.
Lin D et al.·Exp Cell Res
2020
Association of microRNA-related gene XPO5 rs11077 polymorphism with susceptibility to thyroid cancer.
Wen J et al.·Medicine (Baltimore)
2017
Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis.
Hussain HMJ et al.·Hum Genomics
2022
Interrelationship between microsatellite instability and microRNA in gastrointestinal cancer.
Yamamoto H et al.·World J Gastroenterol
2012Review
Exportin-5 Functions as an Oncogene and a Potential Therapeutic Target in Colorectal Cancer.
Shigeyasu K et al.·Clin Cancer Res
2017
Comparison of Pairwise Venous and Fingertip Plasma Using Quantitative Proteomics Based on Data-Independent Acquisition.
Xu G et al.·J Proteome Res
2023
ERK Activation Globally Downregulates miRNAs through Phosphorylating Exportin-5.
Sun HL et al.·Cancer Cell
2016
Melatonin-mediated Inhibition of XPO5 phosphorylation facilitates the chondrogenic differentiation of human bone marrow mesenchymal stem cells by regulating the transport of miR-590-5p.
Su S et al.·Mol Biol Rep
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Locally Advanced Solid TumorsMetastatic Solid Tumors

A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

RECRUITING
NCT03093116Phase PHASE1, PHASE2Turning Point Therapeutics, Inc.Started 2017-03-07
Oral repotrectinib (TPX-0005)

External Resources

Links to major genomics databases and tools