TOP1MT

DNA topoisomerase I mitochondrial, the group of Topoisomerases

Basic information

Region (hg38): 8:143304384-143359979

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.

• not_provided (188 variants)
• not_specified (101 variants)
• Premature_ovarian_insufficiency (1 variants)
• Sensorineural_hearing_loss_disorder (1 variants)

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. These statistics are base on transcript: NM_000052963.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	41	6	52
missense			142	14	8	164
nonsense			5			5
start loss						0
frameshift			4			4
splice donor/acceptor (+/-2bp)			3			3
Total	0	0	159	55	14

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