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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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TNPO3
transportin 3
Chromosome 7 Β· 7q32.1
NCBI Gene: 23534Ensembl: ENSG00000064419.14HGNC: HGNC:17103UniProt: B3KMX1
182PubMed Papers
21Diseases
0Drugs
9Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleoplasmsmall GTPase bindingidentical protein bindingcytosolautosomal dominant limb-girdle muscular dystrophy type 1Fneurodegenerative diseaselysosomal storage diseaseAlzheimer disease
✦AI Summary

TNPO3 (transportin 3) is a nuclear import receptor with dual roles in viral infection and muscular disease. Functionally, TNPO3 mediates nuclear import of diverse cargo through recognition of arginine-serine (SR/RS) repeat-rich and non-classical nuclear localization signals 1. The protein recognizes tyrosine residues within these signals in a phosphorylation-independent manner, with phosphorylation potentially inhibiting binding 1. TNPO3 is critical for HIV-1 infection, facilitating nuclear import of the viral pre-integration complex and enabling nuclear maturation prior to integration 2. Similarly, TNPO3 promotes influenza A virus replication by facilitating viral uncoating and ribonucleoprotein entry into the nucleus 3. During myogenesis, TNPO3 shuttles splicing factor SRSF1 from cytoplasm to nucleus, concentrating in nuclei of differentiated myotubes and regulating alternative splicing necessary for muscle development 4. Pathologically, TNPO3 mutations cause autosomal dominant limb-girdle muscular dystrophy 2 (LGMD D2), with patient muscle biopsies showing aberrant TNPO3 localization, altered SRSF1 expression, and myofibrillar disorganization 56. TNPO3 variants are also associated with antiphospholipid syndrome susceptibility 7. These findings establish TNPO3 as essential for both viral pathogenesis and skeletal muscle homeostasis.

Sources cited
1
TNPO3 facilitates HIV-1 complex import and localization in the nucleus through interaction with viral capsid
PMID: 33572761
2
TNPO3 recognizes non-classical nuclear localization signals containing tyrosines in a phosphorylation-independent manner
PMID: 40360518
3
TNPO3 promotes influenza A virus replication by facilitating viral uncoating and ribonucleoprotein nuclear entry
PMID: 35456945
4
TNPO3 shuttles SRSF1 splicing factor to nuclei during myogenesis for alternative splicing regulation
PMID: 33452620
5
TNPO3 mutations in LGMD D2 cause altered TNPO3 localization and myofibrillar disorganization
PMID: 32690349
6
Nonsense TNPO3 variants cause limb-girdle muscular dystrophy form 1F through premature termination
PMID: 36082569
7
TNPO3 variants are associated with antiphospholipid syndrome susceptibility in genome-wide association studies
PMID: 38973605
Disease Associationsβ“˜21
autosomal dominant limb-girdle muscular dystrophy type 1FOpen Targets
0.72Strong
neurodegenerative diseaseOpen Targets
0.52Moderate
lysosomal storage diseaseOpen Targets
0.49Moderate
Alzheimer diseaseOpen Targets
0.46Moderate
multiple sclerosisOpen Targets
0.46Moderate
Parkinson diseaseOpen Targets
0.46Moderate
muscular dystrophy, limb-girdle, autosomal dominantOpen Targets
0.44Moderate
Autosomal dominant limb-girdle muscular dystrophyOpen Targets
0.37Weak
systemic lupus erythematosusOpen Targets
0.32Weak
autoimmune disorder of musculoskeletal systemOpen Targets
0.28Weak
hypothyroidismOpen Targets
0.27Weak
adolescent idiopathic scoliosisOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
Scapular wingingOpen Targets
0.11Weak
clear cell renal carcinomaOpen Targets
0.11Weak
rheumatoid arthritisOpen Targets
0.09Suggestive
systemic sclerodermaOpen Targets
0.09Suggestive
renal carcinomaOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
HIV-1 infectionOpen Targets
0.07Suggestive
Muscular dystrophy, limb-girdle, autosomal dominant 2UniProt
Pathogenic Variants9
NM_012470.4(TNPO3):c.2767del (p.Arg923fs)Likely pathogenic
Autosomal dominant limb-girdle muscular dystrophy type 1F|Muscular dystrophy, limb-girdle, autosomal dominant
β˜…β˜…β˜†β˜†2024β†’ Residue 923
NM_012470.4(TNPO3):c.1423dup (p.Thr475fs)Likely pathogenic
Autosomal dominant limb-girdle muscular dystrophy type 1F
β˜…β˜†β˜†β˜†2022β†’ Residue 475
NM_012470.4(TNPO3):c.1543del (p.Leu515fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 515
NM_012470.4(TNPO3):c.2760del (p.Arg920fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 920
NM_012470.4(TNPO3):c.1920+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2020
NM_012470.4(TNPO3):c.163C>T (p.Gln55Ter)Pathogenic
Autosomal dominant limb-girdle muscular dystrophy type 1F
β˜…β˜†β˜†β˜†2019β†’ Residue 55
NM_012470.4(TNPO3):c.2430+1G>ALikely pathogenic
Autosomal dominant limb-girdle muscular dystrophy type 1F
β˜…β˜†β˜†β˜†
NM_012470.4(TNPO3):c.2453G>C (p.Arg818Pro)Pathogenic
Autosomal dominant limb-girdle muscular dystrophy type 1F
β˜†β˜†β˜†β˜†2013β†’ Residue 818
NM_012470.4(TNPO3):c.2771del (p.Ter924CysextTer?)Pathogenic
Autosomal dominant limb-girdle muscular dystrophy type 1F
β˜†β˜†β˜†β˜†2013β†’ Residue 924
View on ClinVar β†—
Related Genes
GPN1Shared pathway100%SPRNShared pathway100%FAM53AShared pathway100%RPAINShared pathway100%TMCO6Shared pathway100%FAM53CShared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
91%
Heart
80%
Lung
71%
Ovary
66%
Liver
62%
Gene Interaction Network
Click a node to explore
TNPO3GPN1SPRNFAM53ARPAINTMCO6FAM53C
PROTEIN STRUCTURE
Preparing viewer…
PDB4C0O Β· 2.56 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.65LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.52 [0.42–0.65]
RankingsWhere TNPO3 stands among ~20K protein-coding genes
  • #2,389of 20,598
    Most Researched182 Β· top quartile
  • #2,924of 5,498
    Most Pathogenic Variants9
  • #4,758of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedTNPO3
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Structure, Function, and Interactions of the HIV-1 Capsid Protein.
PMID: 33572761
Life (Basel) Β· 2021
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.90
3
[Analysis of TNPO3 gene variant and clinical phenotype in a neonate with limb-girdle muscular dystrophies form 1F].
PMID: 36082569
Zhonghua Yi Xue Yi Chuan Xue Za Zhi Β· 2022
0.80
4
Structural basis of phosphorylation-independent nuclear import of CIRBP by TNPO3.
PMID: 40360518
Nat Commun Β· 2025
0.70
5
IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.
PMID: 37254791
J Med Virol Β· 2023
0.64