TWNK

Chr 10ARAD

twinkle mtDNA helicase

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

The protein is a mitochondrial DNA helicase that unwinds double-stranded DNA during mitochondrial DNA replication in the mitochondrial matrix. Mutations cause mitochondrial DNA depletion syndrome 7 (hepatocerebral type), Perrault syndrome 5, and progressive external ophthalmoplegia with mitochondrial DNA deletions through both autosomal recessive and autosomal dominant inheritance patterns. The pathogenic mechanism involves impaired mitochondrial DNA replication leading to mitochondrial dysfunction and energy deficiency in affected tissues.

OMIMResearchSummary from RefSeq, OMIM, UniProt
AR/ADLOEUF 0.563 OMIM phenotypes
Clinical SummaryTWNK
🧬
Gene-Disease Validity (ClinGen)
Perrault syndrome 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.003
Z-score 3.42
OE 0.33 (0.200.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.61Z-score
OE missense 0.77 (0.700.85)
301 obs / 390.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.200.56)
00.351.4
Missense OE0.77 (0.700.85)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 10 / 30.3Missense obs/exp: 301 / 390.4Syn Z: -0.62

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC