TPX2

TPX2 microtubule nucleation factor

Basic information

Region (hg38): 20:31739271-31801805

Previous symbols: [ "C20orf2", "C20orf1" ]

Links

ENSG00000088325 ∙ NCBI:22974 ∙ OMIM:605917 ∙ HGNC:1249 ∙ Uniprot:Q9ULW0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TPX2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	3	4
missense			32	4		36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	32	5	3

Variants in TPX2

This is a list of pathogenic ClinVar variants found in the TPX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-31757517-C-T		not specified	Uncertain significance (May 08, 2023)
20-31757552-G-A		not specified	Uncertain significance (May 11, 2022)
20-31760120-G-A		not specified	Uncertain significance (Jun 11, 2021)
20-31766608-C-T			Benign (Jul 31, 2018)
20-31766648-G-A		not specified	Likely benign (Feb 15, 2023)
20-31766651-A-G		not specified	Uncertain significance (Dec 12, 2023)
20-31770449-C-G		not specified	Uncertain significance (Feb 03, 2022)
20-31771626-A-G			Benign (Apr 04, 2018)
20-31771654-C-T		not specified	Uncertain significance (Apr 07, 2023)
20-31775894-G-T		not specified	Uncertain significance (Apr 14, 2022)
20-31775943-C-T		not specified	Uncertain significance (Apr 14, 2022)
20-31777542-C-T			Likely benign (Oct 01, 2024)
20-31777556-G-A		not specified	Uncertain significance (Feb 15, 2023)
20-31777583-A-G		not specified	Uncertain significance (Jul 14, 2021)
20-31777586-A-T		not specified	Uncertain significance (Mar 25, 2024)
20-31777589-A-G		not specified	Uncertain significance (Sep 27, 2022)
20-31777624-C-T		not specified	Uncertain significance (May 30, 2023)
20-31778854-C-A		not specified	Uncertain significance (Sep 27, 2022)
20-31778906-C-T		not specified	Uncertain significance (Apr 01, 2024)
20-31778928-A-C		not specified	Likely benign (Nov 16, 2021)
20-31778940-G-A		not specified	Uncertain significance (May 06, 2024)
20-31778960-T-A		not specified	Uncertain significance (Dec 21, 2023)
20-31782291-A-G		not specified	Uncertain significance (Nov 17, 2023)
20-31782320-C-T		not specified	Uncertain significance (May 26, 2022)
20-31782329-C-T		not specified	Uncertain significance (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPX2	protein_coding	protein_coding	ENST00000300403	16	62535

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000185	125731	0	14	125745	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.490	355	382	0.929	0.0000189	4883
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000620	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Gastric Cancer Network 1;Gene expression (Transcription);role of ran in mitotic spindle regulation;Generic Transcription Pathway;RNA Polymerase II Transcription;Aurora A signaling;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;Cell Cycle, Mitotic;PLK1 signaling events (Consensus)

Recessive Scores

• pRec: 0.0968

Intolerance Scores

• loftool: 0.0807
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.88

Haploinsufficiency Scores

• pHI: 0.928
• hipred: Y
• hipred_score: 0.792
• ghis: 0.678

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.561

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tpx2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; embryo phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: mitotic cell cycle;apoptotic process;cell population proliferation;regulation of G2/M transition of mitotic cell cycle;activation of protein kinase activity;cell division;regulation of mitotic spindle organization;mitotic spindle assembly;regulation of signal transduction by p53 class mediator
• Cellular component: spindle pole;nucleus;nucleoplasm;microtubule organizing center;spindle;cytosol;microtubule;microtubule cytoskeleton;axon hillock;intercellular bridge;mitotic spindle
• Molecular function: protein binding;ATP binding;GTP binding;protein kinase binding;importin-alpha family protein binding