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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TPX2
TPX2 microtubule nucleation factor
Chromosome 20 · 20q11.21
NCBI Gene: 22974Ensembl: ENSG00000088325.17HGNC: HGNC:1249UniProt: Q643R0
255PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
spindle poleprotein bindingprotein kinase bindingprotein serine/threonine kinase activator activityhepatocellular carcinomahypertensionneoplasmnon-small cell lung carcinoma
✦AI Summary

TPX2 (TPX2 microtubule nucleation factor) is a spindle assembly factor essential for normal mitotic spindle formation and microtubule nucleation during cell division 1. The protein mediates Aurora A kinase (AURKA) localization to spindle microtubules and activates AURKA through promoting autophosphorylation at Thr-288 while protecting against dephosphorylation 2. TPX2 function is regulated by importin-alpha binding, which inactivates the protein; liberation from importin-alpha at mitosis onset allows TPX2 to activate AURKA and stimulate microtubule nucleation 3. Beyond mitotic functions, TPX2 plays dual roles in DNA damage response by controlling double-strand break repair pathway choice through ATM-mediated S634 phosphorylation, which promotes BRCA1 recruitment for homologous recombination, while non-phosphorylated TPX2 facilitates 53BP1-mediated non-homologous end joining 4. TPX2 is frequently overexpressed in multiple cancer types including breast cancer, renal cell carcinoma, and multiple myeloma, correlating with increased proliferation, invasion, and poor prognosis 567. The AurkA/TPX2 complex represents a potential oncogenic unit that promotes chr20 instability and tumor progression 2, making it an attractive therapeutic target for cancer treatment.

Sources cited
1
TPX2 is a microtubule-associated protein required for mitotic spindle function
PMID: 26702647
2
TPX2 controls Aurora A kinase activation, localization, and is overexpressed in cancer with correlation to proliferative and aneuploid tumors
PMID: 39195284
3
TPX2 is regulated by importin-alpha binding and plays roles in spindle assembly and DNA damage response
PMID: 24556998
4
TPX2 controls DNA double-strand break repair pathway choice through S634 phosphorylation status
PMID: 39500552
5
TPX2 is upregulated in breast cancer and promotes cell proliferation, migration and invasion
PMID: 26706681
6
TPX2 expression is significantly higher in renal cell carcinoma and associated with poor prognosis
PMID: 27123144
7
TPX2 and AURKA expression levels correlate with poor clinical outcomes in multiple myeloma patients
PMID: 38988264
Disease Associationsⓘ20
hepatocellular carcinomaOpen Targets
0.12Weak
hypertensionOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
lung adenocarcinomaOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
prostate cancerOpen Targets
0.10Suggestive
posterior cortical atrophyOpen Targets
0.09Suggestive
lung cancerOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
gliomaOpen Targets
0.09Suggestive
Nijmegen breakage syndromeOpen Targets
0.08Suggestive
liver cancerOpen Targets
0.08Suggestive
esophageal cancerOpen Targets
0.08Suggestive
gastric carcinomaOpen Targets
0.08Suggestive
osteosarcomaOpen Targets
0.08Suggestive
Malignant Pancreatic NeoplasmOpen Targets
0.07Suggestive
colon carcinomaOpen Targets
0.07Suggestive
urinary bladder carcinomaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BIRC5Protein interaction100%BUB1Protein interaction100%CDKN3Protein interaction100%CENPFProtein interaction100%ECT2Protein interaction100%HMMRProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
66%
Liver
3%
Lung
2%
Heart
1%
Ovary
0%
Gene Interaction Network
Click a node to explore
TPX2BIRC5BUB1CDKN3CENPFECT2HMMR
PROTEIN STRUCTURE
Preparing viewer…
PDB6VPM · 1.58 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.29Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.20 [0.13–0.29]
RankingsWhere TPX2 stands among ~20K protein-coding genes
  • #1,511of 20,598
    Most Researched255 · top 10%
  • #1,062of 17,882
    Most Constrained (LOEUF)0.29 · top 10%
Genes detectedTPX2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Contribution of AurkA/TPX2 Overexpression to Chromosomal Imbalances and Cancer.
PMID: 39195284
Cells · 2024
1.00
2
Maternal ELL3 loss-of-function leads to oocyte aneuploidy and early miscarriage.
PMID: 39820605
Nat Struct Mol Biol · 2025
0.90
3
TPX2.
PMID: 26702647
Curr Biol · 2015
0.80
4
An atlas of RNA-dependent proteins in cell division reveals the riboregulation of mitotic protein-protein interactions.
PMID: 40057470
Nat Commun · 2025
0.72
5
TPX2 serves as a novel target for expanding the utility of PARPi in pancreatic cancer through conferring synthetic lethality.
PMID: 39500552
Gut · 2025
0.70