TOP3B

DNA topoisomerase III beta, the group of Topoisomerases

Basic information

Region (hg38): 22:21957024-21982813

Links

ENSG00000100038 ∙ NCBI:8940 ∙ OMIM:603582 ∙ HGNC:11993 ∙ Uniprot:O95985 ∙ 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 TOP3B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOP3B 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				11	4	15
missense			47	4	3	54
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				2	3	5
non coding				1		1
Total	0	0	49	16	7

Variants in TOP3B

This is a list of pathogenic ClinVar variants found in the TOP3B region.

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

Position	Type	Phenotype	Significance	ClinVar
22-21957128-C-T		not specified	Uncertain significance (Jun 02, 2023)
22-21957163-G-C		not specified	Uncertain significance (Feb 23, 2023)
22-21957193-C-T		not specified	Uncertain significance (May 24, 2024)
22-21957199-C-T		not specified	Uncertain significance (Dec 27, 2023)
22-21957209-C-T		not specified	Uncertain significance (Aug 02, 2022)
22-21957214-C-T		not specified	Uncertain significance (Mar 17, 2023)
22-21957227-C-T		not specified	Uncertain significance (Oct 28, 2023)
22-21957230-C-T		not specified	Uncertain significance (Aug 12, 2021)
22-21957233-G-C		not specified	Uncertain significance (Dec 06, 2023)
22-21957235-T-C		not specified	Uncertain significance (Feb 13, 2024)
22-21957302-C-T		not specified	Uncertain significance (Aug 08, 2023)
22-21957317-G-A			Uncertain significance (Feb 01, 2024)
22-21957326-C-T		not specified	Uncertain significance (Apr 16, 2024)
22-21957328-C-T		not specified	Uncertain significance (Nov 17, 2023)
22-21957386-C-T		not specified	Uncertain significance (Aug 13, 2021)
22-21957413-C-A		not specified	Uncertain significance (Dec 21, 2023)
22-21957413-C-T		not specified	Uncertain significance (Dec 21, 2022)
22-21957428-C-T			Benign (Jul 01, 2023)
22-21957443-C-A		not specified	Uncertain significance (May 03, 2023)
22-21957483-C-T			Likely benign (Oct 01, 2022)
22-21957510-G-A			Benign (Dec 18, 2019)
22-21957524-C-G		not specified	Uncertain significance (Oct 26, 2022)
22-21957568-G-A		not specified	Uncertain significance (Jun 18, 2024)
22-21958485-C-T			Benign (Jul 11, 2018)
22-21958490-A-G		TOP3B-related disorder	Uncertain significance (Aug 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOP3B	protein_coding	protein_coding	ENST00000398793	17	25817

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000214	1.00	125706	1	39	125746	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.23	381	524	0.726	0.0000336	5630
Missense in Polyphen		101	160.15	0.63066		1649
Synonymous	0.139	223	226	0.988	0.0000161	1659
Loss of Function	3.88	14	40.7	0.344	0.00000204	482

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000333	0.000333
Ashkenazi Jewish	0.00	0.00
East Asian	0.000286	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000286	0.000272
South Asian	0.000360	0.000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand than undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Possesses negatively supercoiled DNA relaxing activity. {ECO:0000250}.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Homologous recombination - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.255

Intolerance Scores

• rvis_EVS: -0.48
• rvis_percentile_EVS: 22.75

Haploinsufficiency Scores

• pHI: 0.268
• hipred: Y
• hipred_score: 0.704
• ghis: 0.576

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Top3b
• Phenotype: endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; immune system phenotype; respiratory system phenotype; reproductive system 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); hematopoietic system phenotype; digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: DNA topological change;chromosome segregation
• Cellular component: condensed chromosome;nucleus
• Molecular function: DNA binding;RNA binding;DNA topoisomerase activity;DNA topoisomerase type I activity;protein binding