TOP2B
Basic information
Region (hg38): 3:25597978-25664909
Links
Phenotypes
GenCC
Source:
- 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
- B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (Strong), mode of inheritance: AD
- B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (Moderate), mode of inheritance: AD
- neurodevelopmental disorder (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
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
- not_provided (920 variants)
- not_specified (134 variants)
- TOP2B-related_disorder (24 variants)
- B-cell_immunodeficiency,_distal_limb_anomalies,_and_urogenital_malformations (17 variants)
- See_cases (2 variants)
- Neurodevelopmental_disorder (1 variants)
- TOP2B-related_neurodevelopmental_disorder (1 variants)
- Autism_spectrum_disorder (1 variants)
- Inborn_genetic_diseases (1 variants)
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. These statistics are base on transcript: NM_001330700.2. Only rare variants are included in the table.
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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 188 | 16 | 208 | |||
missense | 422 | 17 | 448 | |||
nonsense | 7 | |||||
start loss | 1 | 1 | ||||
frameshift | 10 | 11 | ||||
splice donor/acceptor (+/-2bp) | 4 | |||||
Total | 3 | 2 | 447 | 206 | 21 |
GnomAD
Source:
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:
- 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