TPX2
protein-codingTPX2 microtubule nucleation factor
Gene summary
Enables several functions, including importin-alpha family protein binding activity; protein kinase binding activity; and protein serine/threonine kinase activator activity. Involved in activation of protein kinase activity; microtubule cytoskeleton organization; and negative regulation of microtubule depolymerization. Located in intercellular bridge; nucleoplasm; and spindle. Is active in spindle. [provided by Alliance of Genome Resources, Jun 2026]
- C20orf2
- C20orf1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007661
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TPX2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012112.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | 3 | 7 | ||
| missense | 91 | 5 | 96 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 97 | 7 | 3 | 107 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036244.2 | 16 | MANE Select | |
| Ensembl | ENSP00000300403.6 | 16 | MANE Select | |
| Ensembl | ENSP00000341145.4 | 17 | Standard | |
| Ensembl | ENSP00000341145.4 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gastric Cancer Network 1
- Gene expression (Transcription)
- role of ran in mitotic spindle regulation
- Generic Transcription Pathway
- RNA Polymerase II Transcription
Biological Process
- mitotic cell cycle
- apoptotic process
- cell population proliferation
- regulation of G2/M transition of mitotic cell cycle
- activation of protein kinase activity
Molecular Function
- protein binding
- ATP binding
- GTP binding
- protein kinase binding
- importin-alpha family protein binding
Cellular Component
- spindle pole
- nucleus
- nucleoplasm
- microtubule organizing center
- spindle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000300403
- Coding exons
- 16
- Length
- 62535
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125745
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.490 | 355 | 382 | 0.929 | 0.0000189 | 4883 |
| Missense (PolyPhen) | 79 | 112.05 | 0.70502 | 1522 | ||
| Synonymous | 0.302 | 130 | 134 | 0.967 | 0.00000656 | 1381 |
| Loss of Function | 5.45 | 4 | 42.2 | 0.0949 | 0.00000235 | 525 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules (PubMed:18663142, PubMed:19208764). Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation (PubMed:18663142, PubMed:19208764). TPX2 is inactivated upon binding to importin- alpha (PubMed:26165940). At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activates AURKA kinase and stimulates local microtubule nucleation (PubMed:26165940). {ECO:0000269|PubMed:18663142, ECO:0000269|PubMed:19208764, ECO:0000269|PubMed:26165940}.;
Recessive Scores
- pRec
- 0.0968
Intolerance Scores
- LoFtool
- 0.0807
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.88
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.561
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |