TOP2A

DNA topoisomerase II alpha, the group of Topoisomerases

Basic information

Region (hg38): 17:40388525-40417896

Previous symbols: [ "TOP2" ]

Links

ENSG00000131747 ∙ NCBI:7153 ∙ OMIM:126430 ∙ HGNC:11989 ∙ Uniprot:P11388 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TOP2A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOP2A 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				4	5	9
missense			65	10	2	77
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	65	14	7

Variants in TOP2A

This is a list of pathogenic ClinVar variants found in the TOP2A region.

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

Position	Type	Phenotype	Significance	ClinVar
17-40389558-T-C		not specified	Uncertain significance (Apr 06, 2024)
17-40389575-G-A		not specified	Uncertain significance (Oct 10, 2023)
17-40389582-T-G		not specified	Uncertain significance (Dec 27, 2022)
17-40389620-G-A		not specified	Uncertain significance (Nov 11, 2024)
17-40389626-C-T		not specified	Uncertain significance (Aug 04, 2024)
17-40389970-T-C		not specified	Uncertain significance (Sep 15, 2021)
17-40390022-A-C		TOP2A-related disorder	Benign (May 30, 2019)
17-40390108-T-C		not specified	Uncertain significance (May 12, 2024)
17-40390129-T-C		not specified	Uncertain significance (Feb 10, 2022)
17-40390141-C-A		not specified	Uncertain significance (Apr 26, 2023)
17-40390141-C-T		not specified	Uncertain significance (Dec 18, 2023)
17-40391509-T-G		not specified	Uncertain significance (May 18, 2023)
17-40391561-T-C			Likely benign (Sep 01, 2022)
17-40391623-C-T		not specified	Uncertain significance (Oct 06, 2024)
17-40392074-C-T		not specified	Likely benign (Oct 17, 2023)
17-40392094-A-G		not specified	Uncertain significance (Mar 29, 2022)
17-40392210-A-G			Benign (Jun 23, 2018)
17-40392277-A-C			Benign (Dec 31, 2019)
17-40392296-G-A		not specified	Uncertain significance (Nov 18, 2022)
17-40392298-G-T		not specified	Uncertain significance (Aug 11, 2022)
17-40392315-C-A		not specified	Uncertain significance (Dec 30, 2023)
17-40392335-G-C		not specified	Uncertain significance (Oct 13, 2023)
17-40392626-A-G		not specified	Uncertain significance (Oct 10, 2023)
17-40392636-C-T		not specified	Uncertain significance (Jan 16, 2024)
17-40392726-T-C		not specified	Uncertain significance (May 16, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOP2A	protein_coding	protein_coding	ENST00000423485	35	29435

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.991	0.00914	124609	0	45	124654	0.000181

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.04	448	762	0.588	0.0000378	10175
Missense in Polyphen		84	275.11	0.30534		3647
Synonymous	1.70	221	256	0.865	0.0000126	2692
Loss of Function	6.75	15	80.2	0.187	0.00000437	1057

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000556	0.000540
Ashkenazi Jewish	0.000103	0.0000993
East Asian	0.0000618	0.0000556
Finnish	0.0000469	0.0000464
European (Non-Finnish)	0.000201	0.000195
Middle Eastern	0.0000618	0.0000556
South Asian	0.000341	0.000294
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity). {ECO:0000250|UniProtKB:Q01320, ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22323612}.
• Pathway: Doxorubicin Pathway (Cancer Cell), Pharmacodynamics;Etoposide Pathway, Pharmacokinetics/Pharmacodynamics;Etoposide Action Pathway;Teniposide Action Pathway;Teniposide Metabolism Pathway;Etoposide Metabolism Pathway;Mitotic G1-G1-S phases;Gastric Cancer Network 1;Gastric Cancer Network 2;Retinoblastoma (RB) in Cancer;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Transcription of E2F targets under negative control by DREAM complex;G0 and Early G1;Mitotic G1-G1/S phases;SUMOylation;Cell Cycle;Cell Cycle, Mitotic;Validated transcriptional targets of deltaNp63 isoforms (Consensus)

Recessive Scores

• pRec: 0.545

Intolerance Scores

• loftool: 0.689
• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.61

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.756
• ghis: 0.592

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Top2a

Zebrafish Information Network

• Gene name: top2a
• Affected structure: neural tube
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: resolution of meiotic recombination intermediates;sister chromatid segregation;hematopoietic progenitor cell differentiation;DNA topological change;DNA ligation;cellular response to DNA damage stimulus;chromosome segregation;female meiotic nuclear division;apoptotic chromosome condensation;embryonic cleavage;regulation of circadian rhythm;positive regulation of apoptotic process;mitotic DNA integrity checkpoint;positive regulation of single stranded viral RNA replication via double stranded DNA intermediate;positive regulation of transcription by RNA polymerase II;rhythmic process;negative regulation of DNA duplex unwinding
• Cellular component: nuclear chromosome;condensed chromosome;nucleus;nucleoplasm;nucleolus;centriole;DNA topoisomerase complex (ATP-hydrolyzing);viral integration complex;protein-containing complex;ribonucleoprotein complex
• Molecular function: magnesium ion binding;DNA binding;chromatin binding;RNA binding;DNA topoisomerase type II (ATP-hydrolyzing) activity;protein kinase C binding;protein binding;ATP binding;protein C-terminus binding;DNA-dependent ATPase activity;drug binding;DNA binding, bending;enzyme binding;protein homodimerization activity;histone deacetylase binding;ubiquitin binding;protein heterodimerization activity