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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TNPO2
transportin 2
Chromosome 19 Β· 19p13.13
NCBI Gene: 30000Ensembl: ENSG00000105576.17HGNC: HGNC:19998UniProt: O14787
76PubMed Papers
21Diseases
0Drugs
16Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTransporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingnuclear localization sequence bindingnuclear import signal receptor activityprotein import into nucleusintellectual developmental disorder with hypotonia, impaired speech, and dysmorphic faciesIntellectual disabilityHypotoniaSeizure
✦AI Summary

TNPO2 encodes transportin-2, a nuclear transport receptor that mediates non-classical nucleocytoplasmic shuttling of over 60 cargo proteins, including developmental and neuronal proteins 1. The protein functions by binding nuclear localization signals in substrate proteins and facilitating their import through nuclear pores via a Ran-dependent mechanism. TNPO2 plays critical roles in neuronal maintenance and function, as demonstrated in Drosophila models where altered expression causes developmental defects, neuronal dysfunction, and lethality in a dosage-dependent manner 1. The protein also regulates nucleocytoplasmic shuttling of estrogen receptor-Ξ± by competing with importin-Ξ± for binding, thereby controlling cytoplasmic retention and nuclear import 2. Pathogenic de novo variants in TNPO2 cause intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic features, with variant effects correlating with their position within the protein domains 1 3. TNPO2 has additional roles in cancer, promoting gastric cancer cell proliferation and serving as a potential bladder cancer biomarker 4 5. The protein is also targeted by interferon-inducible miR-128, which reduces HIV-1 replication by downregulating TNPO3 expression 6.

Sources cited
1
TNPO2 mediates non-classical nucleocytoplasmic shuttling of >60 cargoes and is critical for neuronal function; de novo variants cause developmental delays and neurological deficits
PMID: 34314705
2
TNPO2 regulates nucleocytoplasmic shuttling of estrogen receptor-Ξ± by competing with importin-Ξ± for binding
PMID: 33122699
3
TNPO2 promotes gastric cancer cell proliferation and inhibits apoptosis
PMID: 31605449
4
TNPO2 serves as a potential noninvasive biomarker for bladder cancer
PMID: 38196148
5
TNPO2 expression is regulated by interferon-inducible miR-128, affecting HIV-1 replication
PMID: 31341054
6
Novel TNPO2 variant associated with intellectual developmental disorder and hippocampal neuronal changes
PMID: 41311105
Disease Associationsβ“˜21
intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic faciesOpen Targets
0.68Moderate
Intellectual disabilityOpen Targets
0.50Moderate
HypotoniaOpen Targets
0.50Moderate
microcephalyOpen Targets
0.50Moderate
SeizureOpen Targets
0.50Moderate
genetic disorderOpen Targets
0.34Weak
Neurodevelopmental disorderOpen Targets
0.27Weak
gastric cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.05Suggestive
exudative vitreoretinopathyOpen Targets
0.03Suggestive
exudative vitreoretinopathy 2, X-linkedOpen Targets
0.03Suggestive
cancerOpen Targets
0.02Suggestive
Pick diseaseOpen Targets
0.01Suggestive
Global developmental delayOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
malignant pleural mesotheliomaOpen Targets
0.01Suggestive
bladder transitional cell carcinomaOpen Targets
0.01Suggestive
Miyoshi myopathyOpen Targets
0.01Suggestive
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic faciesUniProt
Pathogenic Variants16
NM_001382241.1(TNPO2):c.466G>T (p.Asp156Tyr)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 156
NM_001382241.1(TNPO2):c.191C>T (p.Ser64Phe)Likely pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜…β˜†β˜†β˜†2025β†’ Residue 64
NM_001382241.1(TNPO2):c.466G>A (p.Asp156Asn)Pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies|TNPO2-related disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 156
NM_001382241.1(TNPO2):c.890+1G>TLikely pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜…β˜†β˜†β˜†2024
NM_001382241.1(TNPO2):c.826G>A (p.Glu276Lys)Likely pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜…β˜†β˜†β˜†2023β†’ Residue 276
NM_001382241.1(TNPO2):c.2174C>A (p.Ala725Asp)Likely pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜…β˜†β˜†β˜†2023β†’ Residue 725
NM_001382241.1(TNPO2):c.1541C>T (p.Pro514Leu)Likely pathogenic
TNPO2-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 514
NM_001382241.1(TNPO2):c.2342C>T (p.Thr781Ile)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 781
NM_001382241.1(TNPO2):c.1643C>T (p.Ser548Phe)Likely pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜…β˜†β˜†β˜†2022β†’ Residue 548
NM_001382241.1(TNPO2):c.2110+1G>CLikely pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜…β˜†β˜†β˜†2022
NM_001382241.1(TNPO2):c.2048G>C (p.Ser683Thr)Likely pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜…β˜†β˜†β˜†2021β†’ Residue 683
NM_001382241.1(TNPO2):c.1471_1474delinsCAAT (p.Lys491_Arg492delinsGlnTrp)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2021β†’ Residue 491
NM_001382241.1(TNPO2):c.1708T>G (p.Trp570Gly)Likely pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜†β˜†β˜†β˜†2025β†’ Residue 570
NM_001382241.1(TNPO2):c.1108T>C (p.Trp370Arg)Pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜†β˜†β˜†β˜†2021β†’ Residue 370
NM_001382241.1(TNPO2):c.1110G>C (p.Trp370Cys)Pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜†β˜†β˜†β˜†2021β†’ Residue 370
NM_001382241.1(TNPO2):c.1637C>T (p.Ala546Val)Pathogenic
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
β˜†β˜†β˜†β˜†2021β†’ Residue 546
View on ClinVar β†—
Related Genes
TNPO1Shared pathway100%IPO8Shared pathway100%IPO11Shared pathway100%NUP153Protein interaction95%IPO13Protein interaction92%IPO9Protein interaction92%
Tissue Expression6 tissues
Brain
100%
Ovary
87%
Bone Marrow
76%
Heart
69%
Lung
47%
Liver
39%
Gene Interaction Network
Click a node to explore
TNPO2TNPO1IPO8IPO11NUP153IPO13IPO9
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O14787
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.23Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.15 [0.10–0.23]
RankingsWhere TNPO2 stands among ~20K protein-coding genes
  • #6,296of 20,598
    Most Researched76
  • #2,409of 5,498
    Most Pathogenic Variants16
  • #633of 17,882
    Most Constrained (LOEUF)0.23 Β· top 5%
Genes detectedTNPO2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila.
PMID: 34314705
Am J Hum Genet Β· 2021
1.00
2
TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis.
PMID: 31605449
Cancer Med Β· 2019
0.90
3
Transportin-2 plays a critical role in nucleocytoplasmic shuttling of oestrogen receptor-Ξ±.
PMID: 33122699
Sci Rep Β· 2020
0.80
4
Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development.
PMID: 36576422
Dev Dyn Β· 2023
0.70
5
Integration of the cancer cell secretome and transcriptome reveals potential noninvasive diagnostic markers for bladder cancer.
PMID: 38196148
Proteomics Clin Appl Β· 2024
0.60