TWNK

Chr 10

twinkle mtDNA helicase

Also known as: ATXN8, C10orf2, IOSCA, MTDPS7, PEO, PEO1, PEOA3, PRLTS5

NCBI Gene: 56652ENSG00000107815UniProt: Q96RR1

This gene encodes a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Aug 2009]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtProgressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3
UniProtMitochondrial DNA depletion syndrome 7
UniProtPerrault syndrome 5

Clinical highlights

Gene-disease validity (ClinGen)
Perrault syndrome 5 · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
2
Active trials
20
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.56
LOEUF
—
Mechanism
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GeneReview available — TWNK
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.56LOEUF
pLI 0.003
Z-score 3.42
OE 0.33 (0.20–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.61Z-score
OE missense 0.77 (0.70–0.85)
301 obs / 390.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.33 (0.20–0.56)
0≤0.351.4
Missense OE?0.77 (0.70–0.85)
0≤0.61.4
Synonymous OE?1.06
0≤1.21.6
LoF obs/exp: 10 / 30.3Missense obs/exp: 301 / 390.4Syn Z: -0.62

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TWNK · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients