TPX2

Chr 20

TPX2 microtubule nucleation factor

Also known as: C20orf1, C20orf2, DIL-2, DIL2, FLS353, GD:C20orf1, HCA519, HCTP4

NCBI Gene: 22974ENSG00000088325UniProt: Q9ULW0

TPX2 encodes a spindle assembly factor that is essential for mitotic spindle formation and activates Aurora kinase A during cell division. Biallelic mutations cause severe microcephaly with simplified gyral pattern, and affected individuals typically present with profound developmental delay and seizures in infancy. This gene is highly intolerant to loss-of-function variants (pLI 1.0, LOEUF 0.22), reflecting its critical role in normal brain development.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
74
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
0.22
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— TPX2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 92 VUS of 144 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 1.000
Z-score 5.45
OE 0.09 (0.05–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.49Z-score
OE missense 0.93 (0.85–1.01)
355 obs / 382.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.05–0.22)
0≤0.351.4
Missense OE0.93 (0.85–1.01)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 4 / 42.2Missense obs/exp: 355 / 382.0Syn Z: 0.30

ClinVar Variant Classifications

144 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic6
VUS92
Likely Benign10
Benign3
10
Pathogenic
6
Likely Pathogenic
92
VUS
10
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
6
0
6
VUS
0
85
7
0
92
Likely Benign
0
5
3
2
10
Benign
0
0
0
3
3
Total090265121

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TPX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Deciphering immune heterogeneity in lung adenocarcinoma via machine learning-based Differential Phenotype Immune Score: TPX2 as a key biomarker for immunotherapy resistance.
Zhang X et al.·Front Immunol
2026
Somatic structural variants drive upper tract urothelial carcinoma muscle invasiveness via activation of TPX2 transcription.
Xu Z et al.·EBioMedicine
2026Open Access
TPX2 promotes gastric cancer progression and angiogenesis via Wnt/β-catenin signaling.
Xu L et al.·Front Oncol
2026Open Access
The Chromatin Protein CFDP1 Activates TPX2 and Promotes Chromosomal Microtubule Nucleation and Spindle Assembly.
Gopinathan G et al.·Int J Mol Sci
2026Open Access
CEP55 promotes prostate cancer progression via TPX2-dependent activation of AURKA-PI3K-AKT signaling and inhibition of ferroptosis.
Xu L et al.·J Biol Chem
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients