TOP3B

protein-coding

DNA topoisomerase III beta, the group of Topoisomerases

Gene summary

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus relaxing the supercoils and altering the topology of DNA. The enzyme interacts with DNA helicase SGS1 and plays a role in DNA recombination, cellular aging and maintenance of genome stability. Low expression of this gene may be related to higher survival rates in breast cancer patients. This gene has a pseudogene on chromosome 22. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Aug 2013]

MANE transcript

NM_001282112.2

Inheritance

—

ClinVar variants

U:133B:22

Top phenotype

TOP3B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr22:21,957,025-21,982,813

External References & Databases

Ensembl (ENSG00000100038)

Transcript & Mutation Effects

hg38 • Region Span ~25.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TOP3B variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 123

TOP3B-related disorderTotal: 25

not providedTotal: 14

TOP3B-related neurodevelopmental conditionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282112.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	13 clinvar	2 clinvar	18
missense			126 clinvar	5 clinvar	2 clinvar	133
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	133	18	4	155

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 72 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001282112.2	RefSeq	NP_001269041.1	17	MANE Select
ENST00000357179.10	Ensembl	ENSP00000349705.5	17	MANE Select
NM_001282113.2	RefSeq	NP_001269042.1	17	Standard
NM_001349845.2	RefSeq	NP_001336774.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fanconi anemia pathway - Homo sapiens (human)
Homologous recombination - Homo sapiens (human)

Biological Process

DNA topological change
chromosome segregation

Molecular Function

DNA binding
RNA binding
DNA topoisomerase activity
DNA topoisomerase type I activity
protein binding

Cellular Component

condensed chromosome
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398793
Coding exons: 17
Length: 25817
Individuals with no LoFs: 125706
Homozygous LoFs: 1
Heterozygous LoFs: 39
Defined: 125746
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.23	381	524	0.726	0.0000336	5630
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00029	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00036	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.255

Intolerance Scores

RVIS EVS: -0.48
RVIS percentile EVS: 22.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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