TOP2B

DNA topoisomerase II beta, the group of Topoisomerases

Basic information

Region (hg38): 3:25597978-25664909

Links

ENSG00000077097 ∙ NCBI:7155 ∙ OMIM:126431 ∙ HGNC:11990 ∙ Uniprot:Q02880 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (Moderate), mode of inheritance: AD
• B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
B-cell immunodeficiency, distal limb anomalies, and urogenital malformations	AD	Allergy/Immunology/Infectious	Among other features, the condition can involve susceptibilty to infections, and awareness may allow preventative measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious; Craniofacial; Genitourinary; Musculoskeletal	31409799; 32128574; 33459963

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TOP2B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOP2B 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			3	157	17	177
missense			311	8	5	324
nonsense			5			5
start loss						0
frameshift			7		1	8
inframe indel			18			18
splice donor/acceptor (+/-2bp)			2			2
splice region			20	75	19	114
non coding			1	133	14	148
Total	0	0	347	298	37

Variants in TOP2B

This is a list of pathogenic ClinVar variants found in the TOP2B region.

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

Position	Type	Phenotype	Significance	ClinVar
3-25598292-GTGCTCTTTGGGCACTTAATTAAACATTGCAA-TTGCAATGTTTAATTAAGTGCCCAAAGAGCAC			Uncertain significance (Dec 14, 2023)
3-25598318-T-C		TOP2B-related neurodevelopmental disorder	Uncertain significance (Dec 20, 2021)
3-25598319-T-A			Likely benign (Dec 13, 2023)
3-25598329-A-T			Uncertain significance (Jun 13, 2022)
3-25598330-C-T		TOP2B-related disorder • not specified	Conflicting classifications of pathogenicity (Jan 01, 2024)
3-25598331-A-ATCATCT			Uncertain significance (Aug 24, 2023)
3-25598334-ATCT-A			Uncertain significance (Jul 31, 2023)
3-25598336-C-G			Uncertain significance (Nov 10, 2022)
3-25598337-T-A			Benign (Jan 31, 2024)
3-25598337-TTCTTCTTCATCAGAC-T			Uncertain significance (Nov 28, 2022)
3-25598346-A-T			Uncertain significance (Mar 23, 2023)
3-25598348-C-A			Uncertain significance (May 26, 2022)
3-25598350-G-T			Uncertain significance (Dec 27, 2023)
3-25598352-C-T			Likely benign (Dec 28, 2023)
3-25598351-A-ACTC			Uncertain significance (Jan 23, 2024)
3-25598357-C-G			Uncertain significance (Oct 19, 2023)
3-25598358-A-G			Benign (Jan 31, 2024)
3-25598358-A-AAAAT			Uncertain significance (Oct 05, 2023)
3-25598360-A-G			Uncertain significance (Aug 19, 2021)
3-25598369-C-A		not specified	Uncertain significance (Jan 23, 2023)
3-25598376-C-T			Likely benign (May 23, 2023)
3-25598383-C-G			Uncertain significance (Jul 29, 2023)
3-25598386-C-A			Uncertain significance (Dec 27, 2023)
3-25598387-C-T		not specified	Uncertain significance (Aug 15, 2023)
3-25598388-G-A			Likely benign (Jun 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOP2B	protein_coding	protein_coding	ENST00000435706	36	66924

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000111	124626	0	26	124652	0.000104

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.86	474	777	0.610	0.0000383	10705
Missense in Polyphen		53	212.73	0.24914		2820
Synonymous	0.865	245	263	0.932	0.0000130	2891
Loss of Function	6.97	12	78.8	0.152	0.00000401	1131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000652	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.000569	0.000501
Finnish	0.000186	0.000186
European (Non-Finnish)	0.0000625	0.0000619
Middle Eastern	0.000569	0.000501
South Asian	0.000133	0.000131
Other	0.000166	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. {ECO:0000269|PubMed:10684600}.
• Disease: DISEASE: Note=A defect in TOP2B is associated with autism spectrum disorder (ASD). {ECO:0000269|PubMed:28343847}.
• Pathway: Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;Etoposide Pathway, Pharmacokinetics/Pharmacodynamics;Etoposide Action Pathway;Etoposide Metabolism Pathway;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;SUMOylation (Consensus)

Recessive Scores

• pRec: 0.375

Intolerance Scores

• loftool: 0.820
• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.28

Haploinsufficiency Scores

• pHI: 0.998
• hipred: Y
• hipred_score: 0.765
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.878

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Top2b
• Phenotype: normal phenotype; 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); embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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); growth/size/body region phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: top2b
• Affected structure: retinal bipolar neuron
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: resolution of meiotic recombination intermediates;sister chromatid segregation;neuron migration;DNA topological change;axonogenesis;forebrain development;mitotic DNA integrity checkpoint;positive regulation of single stranded viral RNA replication via double stranded DNA intermediate
• Cellular component: heterochromatin;nucleus;nucleoplasm;nucleolus;cytosol;viral integration complex;ribonucleoprotein complex
• Molecular function: DNA binding;chromatin binding;DNA topoisomerase type II (ATP-hydrolyzing) activity;protein kinase C binding;ATP binding;protein C-terminus binding;enzyme binding;histone deacetylase binding;metal ion binding;protein heterodimerization activity