TOP1MT

DNA topoisomerase I mitochondrial, the group of Topoisomerases

Basic information

Region (hg38): 8:143304383-143359979

Links

ENSG00000184428 ∙ NCBI:116447 ∙ OMIM:606387 ∙ HGNC:29787 ∙ Uniprot:Q969P6 ∙ 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 TOP1MT gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOP1MT 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	25	8	34
missense			87	9	8	104
nonsense			5			5
start loss						0
frameshift			1			1
inframe indel			4			4
splice donor/acceptor (+/-2bp)			1			1
splice region			5	4	4	13
non coding				15	6	21
Total	0	0	99	49	22

Variants in TOP1MT

This is a list of pathogenic ClinVar variants found in the TOP1MT region.

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

Position	Type	Phenotype	Significance	ClinVar
8-143309443-A-T			Uncertain significance (Mar 24, 2023)
8-143309444-GAAT-G			Uncertain significance (Mar 24, 2023)
8-143309468-G-A			Benign (Jan 06, 2024)
8-143309470-C-T		not specified	Uncertain significance (Aug 16, 2021)
8-143309493-C-T			Likely benign (Sep 13, 2023)
8-143309494-G-A		not specified	Uncertain significance (Dec 12, 2023)
8-143309496-T-G		not specified	Uncertain significance (Feb 10, 2023)
8-143309535-C-T		not specified	Uncertain significance (Apr 06, 2023)
8-143309541-C-T			Uncertain significance (Jan 16, 2024)
8-143309548-G-A			Benign (Oct 05, 2022)
8-143309558-A-G			Benign (Feb 01, 2024)
8-143310051-AC-A			Benign (Jun 05, 2022)
8-143310072-C-T		not specified	Uncertain significance (Aug 17, 2022)
8-143310109-C-T			Likely benign (Aug 10, 2023)
8-143310110-G-C			Uncertain significance (Oct 07, 2022)
8-143310162-G-A			Likely benign (Sep 06, 2022)
8-143310166-C-T			Likely benign (May 23, 2023)
8-143310174-G-A			Uncertain significance (Dec 07, 2021)
8-143310187-C-G		not specified	Uncertain significance (Aug 30, 2021)
8-143310198-G-A			Benign (Feb 01, 2024)
8-143310213-G-A			Likely benign (Dec 09, 2023)
8-143310235-G-A			Likely benign (Sep 01, 2022)
8-143315715-A-T			Likely benign (Feb 25, 2023)
8-143315717-G-A			Benign (Jan 08, 2024)
8-143315757-T-C		not specified	Uncertain significance (May 14, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOP1MT	protein_coding	protein_coding	ENST00000329245	14	55596

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.44e-34	2.00e-7	125367	0	381	125748	0.00152

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.109	393	387	1.02	0.0000255	3914
Missense in Polyphen		146	135.24	1.0796		1548
Synonymous	0.134	163	165	0.987	0.0000120	1143
Loss of Function	-1.70	45	34.3	1.31	0.00000197	368

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00400	0.00393
Ashkenazi Jewish	0.00212	0.00209
East Asian	0.00191	0.00190
Finnish	0.000791	0.000786
European (Non-Finnish)	0.00137	0.00135
Middle Eastern	0.00191	0.00190
South Asian	0.00162	0.00160
Other	0.00149	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Releases the supercoiling and torsional tension of DNA introduced during duplication of mitochondrial DNA 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). {ECO:0000250, ECO:0000269|PubMed:11526219}.

Recessive Scores

• pRec: 0.148

Intolerance Scores

• loftool: 0.985
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.71

Haploinsufficiency Scores

• pHI: 0.185
• hipred: N
• hipred_score: 0.219
• ghis: 0.491

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.190

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Top1mt
• Phenotype: liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: DNA replication;DNA topological change
• Cellular component: nucleus;chromosome;mitochondrion;mitochondrial nucleoid
• Molecular function: DNA binding;DNA topoisomerase type I activity