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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KPNA1
karyopherin subunit alpha 1
Chromosome 3 · 3q21.1
NCBI Gene: 3836Ensembl: ENSG00000114030.14HGNC: HGNC:6394UniProt: P52294
315PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTransporter
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnuclear import signal receptor activityNLS-bearing protein import into nucleusnucleoplasminfluenzatuberculosisHIV infectiondengue disease
✦AI Summary

KPNA1 (karyopherin subunit alpha 1) is a nuclear transport protein that facilitates the translocation of cargo proteins from the cytoplasm to the nucleus by recognizing nuclear localization sequences (NLS) and forming complexes with importin β1 1. Beyond its classical nuclear import function, KPNA1 demonstrates broader cellular roles including axonal transport in neurons, where it exhibits bidirectional motility and associates with endosome/lysosome factors 2. KPNA1 mediates nuclear translocation of several important proteins including NF-κB p65, promoting colon cancer progression through NF-κB signaling activation 3, and RFNG, which contributes to chemotherapy resistance in colorectal cancer 1. The protein also facilitates NSUN2 nuclear localization in bladder cancer, driving RNA m5C modification 4. Disease relevance is significant, as KPNA1 is overexpressed in multiple cancers and its mutations are associated with psychiatric disorders including schizophrenia 5 6. Gene-environment interaction studies demonstrate that KPNA1 deficiency combined with environmental stressors exacerbates psychiatric disorder-related behaviors, suggesting its importance in neurodevelopmental pathways 7. Clinically, KPNA1 represents a potential therapeutic target for both cancer treatment and psychiatric disorders.

Sources cited
1
KPNA1 facilitates nuclear translocation by forming complexes with importin β1 and mediates RFNG nuclear import in chemotherapy resistance
PMID: 39120977
2
KPNA1 functions in axonal transport with bidirectional motility and associates with endosome/lysosome factors
PMID: 40010609
3
KPNA1 mediates NF-κB p65 nuclear translocation and promotes colon cancer progression
PMID: 37038032
4
KPNA1 facilitates NSUN2 nuclear localization driving RNA m5C modification in bladder cancer
PMID: 41423602
5
KPNA1 mutations are associated with psychiatric disorders and behavioral abnormalities
PMID: 34767585
6
KPNA1 is identified as a candidate gene associated with conotruncal heart defects
PMID: 31314787
7
KPNA1 deficiency interacts with environmental factors to exacerbate psychiatric disorder-related behaviors
PMID: 38336912
Disease Associationsⓘ20
influenzaOpen Targets
0.55Moderate
tuberculosisOpen Targets
0.50Moderate
dengue diseaseOpen Targets
0.46Moderate
HIV infectionOpen Targets
0.46Moderate
atrial fibrillationOpen Targets
0.39Weak
HypercholesterolemiaOpen Targets
0.36Weak
cutaneous melanomaOpen Targets
0.27Weak
Abruptio PlacentaeOpen Targets
0.27Weak
Parkinson diseaseOpen Targets
0.14Weak
HypocalcemiaOpen Targets
0.11Weak
cardiac arrhythmiaOpen Targets
0.08Suggestive
Epidermal Inclusion CystOpen Targets
0.08Suggestive
cervical cancerOpen Targets
0.06Suggestive
metabolic diseaseOpen Targets
0.06Suggestive
46,XX gonadal dysgenesisOpen Targets
0.05Suggestive
Testicular regression syndromeOpen Targets
0.05Suggestive
psychiatric disorderOpen Targets
0.05Suggestive
primary ovarian insufficiencyOpen Targets
0.05Suggestive
congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiencyOpen Targets
0.04Suggestive
46,XY sex reversal 11Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RELAProtein interaction100%NFKB1Protein interaction100%RANProtein interaction98%RCC1Protein interaction95%NCBP2Protein interaction92%TERTProtein interaction91%
Tissue Expression6 tissues
Brain
100%
Heart
56%
Lung
50%
Liver
44%
Ovary
31%
Bone Marrow
19%
Gene Interaction Network
Click a node to explore
KPNA1RELANFKB1RANRCC1NCBP2TERT
PROTEIN STRUCTURE
Preparing viewer…
PDB2JDQ · 2.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.29Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.07–0.29]
RankingsWhere KPNA1 stands among ~20K protein-coding genes
  • #1,076of 20,598
    Most Researched315 · top 10%
  • #1,033of 17,882
    Most Constrained (LOEUF)0.29 · top 10%
Genes detectedKPNA1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy.
PMID: 28552616
Mol Cell · 2017
1.00
2
MAPK Signaling-Mediated RFNG Phosphorylation and Nuclear Translocation Restrain Oxaliplatin-Induced Apoptosis and Ferroptosis.
PMID: 39120977
Adv Sci (Weinh) · 2024
0.90
3
Respiratory syncytial virus NS1 inhibits anti-viral Interferon-α-induced JAK/STAT signaling, by limiting the nuclear translocation of STAT1.
PMID: 38938568
Front Immunol · 2024
0.84
4
Direct observation of importin α family member KPNA1 in axonal transport with or without a schizophrenia-related mutation.
PMID: 40010609
J Biol Chem · 2025
0.80
5
Aberrant KIF26B expression promotes bladder cancer progression through driving NSUN2 nuclear localization.
PMID: 41423602
J Hematol Oncol · 2025
0.70