TOMM5
Chr 9translocase of outer mitochondrial membrane 5
Also known as: C9orf105, Tom5, bA613M10.3
The TOMM5 protein is a component of the translocase of the outer mitochondrial membrane (TOM) complex, which is essential for importing cytosolic proteins into mitochondria and also plays a role in mitophagy regulation. Pathogenic variants in TOMM5 cause autosomal recessive mitochondrial complex assembly factor 5 deficiency, resulting in severe early-onset mitochondrial disease with developmental delay, hypotonia, and metabolic abnormalities. This gene shows moderate constraint against loss-of-function variants, consistent with its essential role in mitochondrial protein import.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TOMM5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools