TIMM8A

Chr XXLR

translocase of inner mitochondrial membrane 8A

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.871 OMIM phenotype
Clinical SummaryTIMM8A
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Gene-Disease Validity (ClinGen)
deafness dystonia syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.
📖
GeneReview available — TIMM8A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.87LOEUF
pLI 0.652
Z-score 1.71
OE 0.00 (0.000.87)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
1.15Z-score
OE missense 0.47 (0.320.70)
17 obs / 36.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.87)
00.351.4
Missense OE0.47 (0.320.70)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 0 / 3.4Missense obs/exp: 17 / 36.6Syn Z: -0.64

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TIMM8A · 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
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC