TOP1

DNA topoisomerase I, the group of Topoisomerases

Basic information

Region (hg38): 20:41028821-41124487

Links

ENSG00000198900 ∙ NCBI:7150 ∙ OMIM:126420 ∙ HGNC:11986 ∙ Uniprot:P11387 ∙ 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 TOP1 gene.

• not provided (7 variants)
• Inborn genetic diseases (5 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOP1 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				1	5	6
missense			5		1	6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	5	1	6

Variants in TOP1

This is a list of pathogenic ClinVar variants found in the TOP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-41061479-G-A			Benign (Dec 31, 2019)
20-41076256-C-T			Benign (Dec 31, 2019)
20-41077586-G-A		not specified	Uncertain significance (Sep 27, 2022)
20-41084482-C-T			Benign (Nov 20, 2018)
20-41084486-A-C		not specified	Uncertain significance (Jul 09, 2021)
20-41084539-G-A		TOP1-related disorder	Likely benign (Jul 25, 2019)
20-41084548-A-G		TOP1-related disorder	Benign (Sep 21, 2020)
20-41097224-A-C		not specified	Uncertain significance (Jul 05, 2023)
20-41100127-G-A			Benign (Oct 17, 2018)
20-41100181-C-T			Likely benign (Dec 31, 2019)
20-41101262-A-T		Autism spectrum disorder	association (-)
20-41101297-G-A		DNA topoisomerase I, camptothecin-resistant	Pathogenic (Jul 01, 2002)
20-41112919-C-T		TOP1-related disorder	Likely benign (Apr 09, 2019)
20-41114060-C-T		not specified	Uncertain significance (Dec 19, 2023)
20-41114115-A-G		-	no classification for the single variant (-)
20-41116318-G-G		-	no classification for the single variant (-)
20-41118221-T-C		TOP1-related disorder	Likely benign (Oct 28, 2019)
20-41118228-A-G		not specified	Uncertain significance (Feb 26, 2024)
20-41121785-G-A		TOP1-related disorder	Benign/Likely benign (Dec 30, 2019)
20-41122038-G-A		not specified	Uncertain significance (Mar 31, 2022)
20-41122043-G-C		not specified	Uncertain significance (Dec 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOP1	protein_coding	protein_coding	ENST00000361337	21	95670

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.20e-8	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.47	156	411	0.379	0.0000222	5162
Missense in Polyphen		11	143.53	0.076639		1747
Synonymous	0.710	127	138	0.923	0.00000704	1252
Loss of Function	6.57	0	50.3	0.00	0.00000304	597

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter. {ECO:0000250|UniProtKB:Q13472, ECO:0000269|PubMed:14594810, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:22904072, ECO:0000269|PubMed:2833744}.
• Disease: DISEASE: Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98. {ECO:0000269|PubMed:10556215}.
• Pathway: Irinotecan Pathway, Pharmacodynamics;Irinotecan Action Pathway;Irinotecan Metabolism Pathway;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;AndrogenReceptor;SUMOylation;Caspase Cascade in Apoptosis (Consensus)

Recessive Scores

• pRec: 0.808

Intolerance Scores

• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.69

Haploinsufficiency Scores

• pHI: 0.996
• hipred: Y
• hipred_score: 0.831
• ghis: 0.594

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.956

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Top1
• 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)

Gene ontology

• Biological process: DNA replication;DNA topological change;chromatin remodeling;chromosome segregation;circadian rhythm;programmed cell death;viral process;phosphorylation;peptidyl-serine phosphorylation;circadian regulation of gene expression;embryonic cleavage;response to drug
• Cellular component: nuclear chromosome;P-body;fibrillar center;nucleus;nucleoplasm;nucleolus;DNA topoisomerase complex (ATP-hydrolyzing);replication fork protection complex;protein-DNA complex;perikaryon
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA binding;chromatin binding;double-stranded DNA binding;single-stranded DNA binding;RNA binding;DNA topoisomerase type I activity;protein serine/threonine kinase activity;protein binding;ATP binding;protein domain specific binding;supercoiled DNA binding