TIMM8A

Chr X

translocase of inner mitochondrial membrane 8A

Also known as: DDP, DDP1, DFN1, MTS, TIM8

NCBI Gene: 1678 ENSG00000126953 UniProt: O60220

The TIMM8A protein functions as a mitochondrial intermembrane chaperone that imports and inserts multi-pass transmembrane proteins into the mitochondrial inner membrane, protecting hydrophobic precursors from aggregation during transport. Mutations cause Mohr-Tranebjaerg syndrome (also called Deafness Dystonia Syndrome) and Jensen syndrome, both X-linked recessive conditions characterized by opticoacoustic nerve atrophy and additional features including dystonia and muscle weakness. The pathogenic mechanism involves defective mitochondrial protein import leading to mitochondrial dysfunction.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This translocase is involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS) and it is postulated that MTS/DDS is a mitochondrial disease caused by a defective mitochondrial protein import system. Defects in this gene also cause Jensen syndrome; an X-linked disease with opticoacoustic nerve atrophy and muscle weakness. This protein, along with TIMM13, forms a 70 kDa heterohexamer. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Mar 2009]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMohr-Tranebjaerg syndrome

Clinical highlights

Gene-disease validity (ClinGen)

deafness dystonia syndrome · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.87

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TIMM8A