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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KPNA5
karyopherin subunit alpha 5
Chromosome 6 · 6q22.1
NCBI Gene: 3841Ensembl: ENSG00000196911.12HGNC: HGNC:6398UniProt: A0A8V8TL88
121PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolprotein bindingnuclear import signal receptor activityNLS-bearing protein import into nucleusdengue diseaseinfluenzatransient ischemic attackresponse to xenobiotic stimulus
✦AI Summary

KPNA5 is a nuclear import adapter protein that facilitates transport of proteins containing nuclear localization signals (NLS) from the cytoplasm to the nucleus via the importin pathway 1. It functions by recognizing and binding to classical and non-classical NLS motifs in cargo proteins, forming complexes with KPNB1 that are transported through nuclear pores in a Ran-GTP dependent manner 1. KPNA5 plays critical roles in cellular stress responses by mediating nuclear translocation of transcription factors like NRF2, which regulates antioxidant pathways 2. The protein is targeted by miR-153, and disruption of the miR-153-KPNA5-NRF2 axis contributes to oxidative stress and cognitive impairment in chr6 cerebral hypoperfusion 2. In cancer biology, KPNA5 functions as a tumor suppressor in ovarian cancer by importing PTPN4 into the nucleus, where it inhibits STAT3 phosphorylation and downstream oncogenic signaling 3. KPNA5 is also exploited by viral pathogens, particularly Ebola virus VP24 protein, which binds to KPNA5 to gain nuclear access while simultaneously blocking STAT1 nuclear import and interferon signaling 451. Expression changes in KPNA5 are associated with various pathological conditions including cancer drug resistance and cellular senescence 67.

Sources cited
1
KPNA5 functions as nuclear import adapter protein recognizing NLS motifs and requires simultaneous cargo binding for nuclear trafficking
PMID: 40872766
2
KPNA5 mediates NRF2 nuclear translocation and is targeted by miR-153 in chronic cerebral hypoperfusion
PMID: 40816766
3
KPNA5 functions as tumor suppressor in ovarian cancer by importing PTPN4 to inhibit STAT3 signaling
PMID: 40145330
4
Ebola virus VP24 binds KPNA5 to gain nuclear access and block interferon signaling
PMID: 28812539
5
VP24-KPNA5 interaction is critical for Ebolavirus pathogenicity through interferon antagonism
PMID: 29140409
6
KPNA5 expression changes are associated with anthracycline resistance in breast cancer
PMID: 25695524
7
KPNA5 is involved in cell cycle regulation and senescence pathways
PMID: 26029164
Disease Associationsⓘ20
dengue diseaseOpen Targets
0.46Moderate
influenzaOpen Targets
0.46Moderate
transient ischemic attackOpen Targets
0.32Weak
Non-Neoplastic Bile Duct DisorderOpen Targets
0.27Weak
response to xenobiotic stimulusOpen Targets
0.27Weak
Abruptio PlacentaeOpen Targets
0.25Weak
ovarian cancerOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.04Suggestive
atrial fibrillationOpen Targets
0.04Suggestive
Hernia of the abdominal wallOpen Targets
0.04Suggestive
Inguinal herniaOpen Targets
0.03Suggestive
atrial flutterOpen Targets
0.03Suggestive
poisoningOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.02Suggestive
COVID-19Open Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
ovarian carcinomaOpen Targets
0.01Suggestive
SepsisOpen Targets
0.01Suggestive
septic shockOpen Targets
0.01Suggestive
pachyonychia congenitaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KPNA4Shared pathway100%KPNA7Shared pathway100%NUP153Protein interaction100%NUP50Protein interaction87%ASTN2Protein interaction82%BLOC1S6Protein interaction79%
Tissue Expression6 tissues
Ovary
100%
Brain
82%
Bone Marrow
62%
Heart
41%
Lung
28%
Liver
16%
Gene Interaction Network
Click a node to explore
KPNA5KPNA4KPNA7NUP153NUP50ASTN2BLOC1S6
PROTEIN STRUCTURE
Preparing viewer…
PDB4U2X · 3.15 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.90LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.63 [0.45–0.90]
RankingsWhere KPNA5 stands among ~20K protein-coding genes
  • #3,883of 20,598
    Most Researched121 · top quartile
  • #8,105of 17,882
    Most Constrained (LOEUF)0.90
Genes detectedKPNA5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Investigating Ebola virus pathogenicity using molecular dynamics.
PMID: 28812539
BMC Genomics · 2017
1.00
2
Ebolavirus interferon antagonists-protein interaction perspectives to combat pathogenesis.
PMID: 29140409
Brief Funct Genomics · 2018
0.90
3
KPNA5 Suppresses Malignant Progression of Ovarian Cancer Through Importing the PTPN4 Into the Nucleus.
PMID: 40145330
Cancer Med · 2025
0.80
4
The Biophysical Basis for Karyopherin-Dependent Ebola Virus VP24 Nuclear Transport.
PMID: 40872766
Viruses · 2025
0.70
5
PMID: 40816766
J Neurosci · 2025
0.60