TOP1MT

Chr 8

DNA topoisomerase I mitochondrial

The encoded mitochondrial DNA topoisomerase relieves supercoiling tension during mitochondrial DNA replication and transcription by transiently cleaving and rejoining DNA strands. Mutations cause infantile-onset spinocerebellar ataxia with mitochondrial encephalomyopathy, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 1.68), with affected patients presenting with progressive neurodegeneration involving the cerebellum and skeletal muscle.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.68
Clinical SummaryTOP1MT
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.68LOEUF
pLI 0.000
Z-score -1.70
OE 1.31 (1.031.68)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.11Z-score
OE missense 1.02 (0.931.10)
393 obs / 386.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.31 (1.031.68)
00.351.4
Missense OE1.02 (0.931.10)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 45 / 34.3Missense obs/exp: 393 / 386.9Syn Z: 0.13

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TOP1MT · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC